UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEM ICAL SAFET Y AND 

POLLUT ION PREVENT ION 

MEMORANDUM 

Date: 14-SEP-2015 

SUBJECT: Chlorsulfuron. Draft Human I lealth Risk Assessment in Support of Registration 

Review. 

PC Code: 11860 1 DP Barcode: 0425536 

Decision No.: 499856 Registration Nos.: Various 

Petition No.: None Regulatory Action: Registration Review 

Assessment Type: Single Chemical Aggregate Reregistration Case No.: 7265-1 

TXR No.: None CAS No.: 64902-72-3 

MRID No.: None 40 CFR: § 180.405 

FROM: Julie Van Als. tine, M.P.H., Environmental Hea lth Scientist Q}O-~ . I/ .1. 

Monica 

Yung Yang, 

Hawkins

Ph.D.

, Ph.D.

, Toxicologist 

, M.P.H., Envi}~mental ~7 G. Health 

~uScientist · IY{_ ~ ~ 

Risk Assessment Branch VI (RAB VI) 

Health Effects Division (HED; 7509P) 

THROUGH: Donna Davis, Acting Branch Chief~ t~_.._~~~--"-.C.,...--

TO: 

RAB VJ!HED (7509P) 

Kelley Sherman/Miguel Zavala 

Risk Management and Implementation Branch JII (RMIB W ) 

Pesticide Re-evaluation Division (PRD; 7508P) 

As part of Registration Review, PRD of the Office of Pesticide Programs (OPP) has requested 

that HED evaluate the hazard and exposure data and conduct occupational and residential 

exposure assessments, as needed, to estimate the risk to human health that will result from the 

currencly registered uses of pesticides. This document evaluates the existing uses of 

chlorsulfuron as part of Registration Review and represents the draft risk assessment (ORA). 

The Agency is reviewing all the sulfonylurea herbicides jointly under Registration Review. 

Since the last human health risk assessment (F. Fort et al., I 8-JUL-2002; 0266070) and scoping 

document (M. Hawkins et al., 6-0EC-2012; 0403355), the following updates have been 

incorporated for chlorsulfuron: 

• The toxicological endpoints and points of departure (PODs) were reevaluated 

considering the new toxicology data that have been submilled since the last risk 

assessment. 

• The occupational risk assessment has been updated to incorporate new science policies. 

• A spray drift assessment was completed as part of Registration Review 

• A refined-screen estimated drinking water concentration (EDWC) was used to assess 

chlorsu/.furon dietary exposure and risk. 

Page I of30 
Chlorsulfuron Human Health Risk Assessment 0425536 

Table of Contents 

I .0 Executive Summary ............................ ................................. .......................... ........................... 3 

2.0 HED Reco1nn1endations ....................................................................................................... ... .. 4 

2.1 Tolerances Considerations ......................................................................................................... 4 

3.0 Ingredient Profile ...................................................................................................................... 4 

3. 1 Chemical Identity and Physical/Chemical Properties ............................................................... .4 

3.2 Use Pattern ................................................................................................................................. 5 

3.3 Anticipated Exposure Pathways .................................................................................. ............... 6 

3.4 Consideration of Environmental Justice ..................................................................................... 6 

4.0 Hazard Identification/Toxicology .................. .... ................. ...................................................... 6 

4.1 Summary of Toxicological Effects ............................................................................................. 7 

4.2 Safety Factor for Infants and Children (FQPA SF) .................................................................... 7 

4.3 Toxicity Endpoint and Point of Departure Selections ................................................................ 7 

4.4 Endocrine Disruption ................................................................................................................. 8 

5.0 Dietary Exposure and Risk Assessment ................................................................................... 9 

5. I Residue Chem is try ..................................................................................................................... 9 

5.2 Drinking Water. ........................................................................................................................ I 0 

5.3 Dietary (Food + Drinking Water) Risk Assessment ................................................................ 10 

6.0 Residential (Non-Occupational) Exposure and Risk Assessment .......................................... I I 

6.1 Spray Drift ......................................................................................................................... I I 

6.1.1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications .......... 11 

6.2 Residential Bystander Post-Application Inhalation Exposure .......................................... 12 

7.0 Aggregate Exposure and Risk Assessment .................. ........................................................... 12 

8.0 Cumulative Exposure/Risk Characteri zation .......................................................................... I 3 

9.0 Occupational Exposure/Risk Characterization ....................................................................... 13 

9.1 Occupational Handler Exposure/Risk Estimates ...................................................................... 13 

9.2 Occupational Post-Application Exp0sure/Risk Estimates ........................................................ 16 

9.2. I Occupational Post-application Inhalation Exposure/Risk Estimates ....................... 16 

10.0 Public Health, Pesticide Epidemiology, and Human Incidence Data .................................. I 7 

I 1.0 References ............................................................................................................................. 18 

Appendix A. Toxicology Profile Tables ...................................................................................... I 9 

Appendix 8. Chemical Identity ................................................................................................... 23 

Appendix C. Analytical Standards for Chlorsulfuron .............................................. .................... 24 

Appendix D. Dietary Exposure/Risk Modeling Input and Output Files ...................................... 25 

Appendix E. Occupational Non-cancer Algorithms .................................................................... 27 

Appendix F. Spray Drift Detailed Description ............................................................................. 29 

Appendix G. DFR Data Waiver Rationale .................................................................................. 30 

Appendix H. Review of Human Research ................................................................................... 30 

Page 2 of30 
Chlorsulfuron Human Health Risk Assessment D425536

Page 3 of 30

1.0 Executive Summary

Chlorsulfuron is a sulfonylurea herbicide that is used to control broadleaf weeds on a variety of 

agricultural crops. It is currently registered for use on barley, grasses grown for seed, oats, 

pastures, and rangeland, rights-of-way, triticale, wheat, and industrial and commercial turf. This 

document addresses exposures and risk estimates from the registered uses of chlorsulfuron using

worst-case exposure scenarios (e.g., highest application rates and highest exposure scenarios).

The toxicity database for chlorsulfuron is adequate to support current registration requirements; 

currently, no additional toxicological studies are required. The Hazard and Science Policy 

Council (HASPOC) waived the requirement for the 21-day dermal toxicity, subchronic 

inhalation, immunotoxicity, and neurotoxicity (acute and subchronic) studies for chlorsulfuron

(TXR#0056439, TXR# 0056723). A rat two-generation reproduction study was submitted since 

the last risk assessment (D266070, F. Fort). The toxicological endpoints and PODs were 

reevaluated considering the new toxicology data. All of the endpoints for risk assessment remain 

the same as those used in the previous assessment. 

The existing residue chemistry database for chlorsulfuron is complete and adequate for risk 

assessment purposes. No additional residue chemistry data are required at this time. 

HED has conducted a chronic dietary exposure and risk assessment for chlorsulfuron using 

tolerance-level residues in foods and EDWCs provided by the Environmental Fate and Effects 

Division (EFED). Chronic dietary exposure and risk estimates (food and drinking water) are 

≤14% of the chronic population adjusted dose (cPAD) and are not of concern for the general 

U.S. population or any other population subgroup. HED did not conduct an acute dietary 

exposure and risk assessment due to the lack of an appropriate endpoint for acute dietary 

assessment. Chlorsulfuron is classified as “not likely to be carcinogenic to humans”; therefore, 

cancer risk is not a concern.

There are no registered residential uses or uses resulting in direct residential exposure associated 

with chlorsulfuron. Therefore, residential handler and conventional residential post-application 

exposure assessments were not conducted. A quantitative spray drift assessment was conducted

to assess indirect exposure in residential settings. Risk estimates from groundboom and aerial 

applications are not of concern from the field edge for all scenarios considered. During 

Registration Review, the Agency will use the Volatilization Screening Analysis to determine if 

data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is 

required for chlorsulfuron.

For chlorsulfuron, aggregate exposure and risk estimates are equivalent to the dietary exposure 

and risk estimates; therefore, aggregate risks are not of concern. 

The occupational handler exposure estimates based on the scenario with the highest application 

rate and amount handled result in short- and intermediate-term dermal and inhalation margins of 

exposure (MOEs) that range from 360 to 40,000 and are not of concern to HED (i.e., MOEs ≥ 

the level of concern (LOC) of 100). Occupational post-application exposure estimates result in

dermal MOEs that range from 2,300 to 190,000 and are not of concern to HED on the day of 

application (i.e., MOEs ≥ LOC). Based on the Agency’s current practices, a quantitative noncancer occupational post-application inhalation exposure assessment was not performed for 

chlorsulfuron. 
Chlorsulfuron Human Health Risk Assessment D425536

Page 4 of 30

The restricted entry interval (REI) of 4 or 12 hours specified on the registered labels is based on 

the acute toxicity of chlorsulfuron. Upon review of the criteria for the active ingredient only, it 

appears that chlorsulfuron is consistent with the criteria in PRN 95-3 that allow for a 4-hour REI. 

Note: The PR Notice also includes similar criteria for the end-use product. These criteria have 

not been evaluated by HED. Based solely on the active ingredient criteria, HED would 

recommend for reduction of the REI for chlorsulfuron.

HED has not identified any risk concerns associated with the registered uses of chlorsulfuron. 

There are no data gaps that would require submission of additional toxicity, residue chemistry, or 

exposure data.

2.0 HED Recommendations

2.1 Tolerances Considerations

The existing tolerances for residues of chlorsulfuron (40 CFR §180.405) are supported by the 

available residue chemistry data. Codex has not established maximum residue limits (MRLs) for 

residues of chlorsulfuron. The established Canadian MRLs for residues of chlorsulfuron are 

harmonized with U.S. tolerances. 

The 40 CFR entry for chlorsulfuron is broken out into two sections: 40 CFR §180.405(a)(1) and 

40 CFR §180.405(a)(2), with 40 CFR §180.405(a)(1) indicating that the parent and 5-hydroxy 

metabolite should be measured for tolerance enforcement purposes and 40 CFR §180.405(a)(2)

indicating that only parent should be measured for enforcement purposes. The HED Metabolism 

Committee determined that the residue of concern for risk assessment and enforcement in plant 

and livestock commodities is the parent only (Memos, J. Abbotts, 04/11/1995, D213534, and J. 

Abbotts, 08/09/1995, D217473). HED notes that as previously recommended, the tolerance 

expression in 40 CFR §180.405 should be revised to reflect the recommendations of the 

Metabolism Committee (Memo, F. Fort et al., 07/18/02; D266070). The established tolerances 

in 40 CFR §180.405(a)(1) and 40 CFR §180.405(a)(2) should be merged into one section, 40 

CFR §180.405(a). The established tolerance values are not impacted by this change. The 

tolerance expression for chlorsulfuron in 40 CFR §180.405(a) should be revised to state the 

following:

(a) General. Tolerances are established for residues of chlorsulfuron, 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 

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

yl)amino]carbonyl]benzenesulfonamide) in or on the commodity.

3.0 Ingredient Profile

3.1 Chemical Identity and Physical/Chemical Properties

The chemical structure and nomenclature of chlorsulfuron and a description of the 

physicochemical properties of chlorsulfuron are provided in Appendix B. 
Chlorsulfuron Human Health Risk Assessment D425536

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3.2 Use Pattern

Chlorsulfuron is currently registered for use on barley, grasses grown for seed, oats, pastures, 

rangeland, rights-of-way, triticale, wheat, and industrial and commercial turf. The end-use 

products registered with chlorsulfuron are formulated as water-dispersible granules (WDG)/dry 

flowable (DF) formulations. The registered products are applied either with aerial, groundboom, 

hand-held, or backpack equipment. The single application rates of the registered uses for 

chlorsulfuron range from 0.016 to 0.14 lb ai/A. 

Table 3.2 provides a summary of the highest application rate of the registered uses for 

chlorsulfuron. 

Table 3.2. Summary of Registered Uses of Chlorsulfuron.

Application

Equipment Formulation 

Maximum 

Application

Rate REI Use Directions and Limitations

Barley

Groundboom, 

Aerial WDG/DF 0.016 lb ai/A 4 hours

Do not apply this product 

through any type of 

irrigation system.

Non-Crop Site: Industrial and Commercial Turf

Groundboom,

Aerial DF 0.02 lb ai/A 4 hours

Do not apply through any 

type of irrigation system.

Do not use on lawns, 

walks, driveways, tennis 

courts, or similar areas.

Grasses Grown for Seed

Groundboom, 

Aerial WDG/DF 0.01 lb ai/A 4 hours

Do not apply this product 

through any type of 

irrigation system.

Oats

Groundboom, 

Aerial WDG/DF 0.02 lb ai/A 4 hours

Do not apply this product 

through any type of 

irrigation system.

Non-Crop Site: Agricultural Rights of Way/Fence Rows/Hedge Rows

Handgun WDG/DF

0.14 lb ai/A

(0.0014 lb 

ai/gallon)

4 hours

Do not apply this product 

through any type of 

irrigation system.

Pastures, Rangeland

Groundboom, 

Aerial WDG/DF 0.06 lb ai/A 4 hours

Do not apply this product 

through any type of 

irrigation system.

Triticale

Groundboom,

Aerial WDG/DF 0.02 lb ai/A 4 hours

Do not apply this product 

through any type of 

irrigation system.

Wheat

Groundboom, 

Aerial WDG/DF 0.02 lb ai/A 4 or 12 hours

Do not apply this product 

through any type of 

irrigation system.

WDG = water-dispersible granule; DF = dry flowable
Chlorsulfuron Human Health Risk Assessment D425536

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3.3 Anticipated Exposure Pathways

Individuals may be exposed to chlorsulfuron via their diet (food and drinking water). There are 

no registered uses for chlorsulfuron that will result in direct non-occupational exposures. 

However, there is the potential for indirect exposure (incidental oral and dermal) to chlorsulfuron

related to spray drift. Agricultural workers may be exposed (dermal and inhalation) to 

chlorsulfuron during mixing, loading, and/or applying the herbicide and entering previously 

treated areas. Based on the use pattern for chlorsulfuron, short- and intermediate-term dermal 

and inhalation exposures for occupational handlers are expected; long-term exposures (greater 

than 6 months) are not anticipated. The chlorsulfuron labels require handlers to wear baseline 

attire (i.e., a long-sleeved shirt, long pants, shoes plus socks) and chemical-resistant gloves. This 

risk assessment considers all of the aforementioned exposure pathways based on the existing 

uses of chlorsulfuron.

3.4 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://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf). As a part of every 

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

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

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

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

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

Agriculture’s (USDA’s) National Health and Nutrition Examination Survey/What We Eat in 

America, (NHANES/WWEIA), are used in pesticide risk assessments for all registered food uses 

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

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

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

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

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

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

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

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

patterns among specific subgroups.

4.0 Hazard Identification/Toxicology

The toxicology database for chlorsulfuron is complete and adequate for risk assessment. The 

HASPOC waived the requirement for the 21-day dermal toxicity, subchronic inhalation, 

immunotoxicity, and neurotoxicity (acute and subchronic) studies for chlorsulfuron

(TXR#0056439, TXR# 0056723). A rat two-generation reproduction study was submitted since 

the last risk assessment (F. Fort et al., 18-JUL-2002; D266070). The toxicological endpoints and 

PODs were reevaluated considering the new toxicology data. The TOXLINE (National Library 

of Medicine) database literature search did not identify any new toxicological information not 

already considered. All of the endpoints for risk assessment remain the same as those used in the 

previous assessment. See Appendix A for the toxicology profile tables for chlorsulfuron. 
Chlorsulfuron Human Health Risk Assessment D425536

Page 7 of 30

4.1 Summary of Toxicological Effects

The chronic toxicity data provide no evidence that chlorsulfuron is particularly toxic to any 

organ or tissue. The most prevalent effect observed across studies was decreased body weight

and body weight gain. In the developmental toxicity studies in rats and rabbits, decreased fetal 

body weight was observed at or above the limit dose in the presence of maternal toxicity. No 

reproductive toxicity was observed in the updated two-generation reproduction study. There is 

no evidence of neurotoxicity, developmental, or reproductive toxicity. Chlorsulfuron is

classified as “not likely to be carcinogenic to humans” based upon lack of evidence of 

carcinogenicity in rats and mice and the lack of effects in mutagenicity studies.

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

(Toxicity Category III or IV). It is not an eye or skin irritant, and is not a skin sensitizer.

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

administration. There were no remarkable differences in absorption, distribution, or excretion of 

chlorsulfuron related to sex, dose, or route of administration. 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 three days after dosing, with the highest concentrations observed in the liver 

and whole blood in both sexes.

4.2 Safety Factor for Infants and Children (FQPA SF)

HED has recommended that the required 10x Food Quality Protection Act (FQPA) Safety Factor 

(SF) be reduced to 1x for chlorsulfuron. The toxicology database is complete, there is no 

evidence of increased susceptibility, no concerns/residual uncertainties with regard to pre- and/or 

postnatal toxicity, and no concern for neurotoxicity. In addition, exposure estimates are unlikely 

to underestimate risk.

4.3 Toxicity Endpoint and Point of Departure Selections

The toxicological endpoint/PODs selected for risk assessment remain the same as in previous 

assessments. The no-observed adverse-effect levels (NOAELs) and lowest-observed adverseeffect levels (LOAELs) have not been revised to reflect current policy and are considered 

conservative. Therefore, the endpoints/PODs selected for risk assessment may be conservative.

The PODs selected for risk assessment are protective of the effects observed in the chlorsulfuron

database. In the previous risk assessment document, the FQPA factor was reduced to 3x and 

applied to risk assessments to address data deficiencies regarding the reproduction study. 

Subsequently, an acceptable two-generation reproduction study in rats was submitted which did 

not show any adverse effects on reproduction or toxicity to the offspring. Therefore, the 3x 

database uncertainty factor was removed. The total UF for all exposure scenarios is 100x (10x 

for interspecies extrapolation, 10x for intraspecies variation, and 1x for FQPA Safety Factor

when applicable).
Chlorsulfuron Human Health Risk Assessment D425536

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Table 4.3.1. Toxicological Doses and Endpoint for Chlorsulfuron for Use in Dietary and Non-Occupational 

Human Health Risk Assessments.

Exposure/Scenario Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, Level of Concern 

for Risk Assessment

Study and Toxicological 

Effects

Acute Dietary

(All populations)

No appropriate endpoint attributable to a single dose was identified including developmental toxicity 

studies in rats and rabbits.

Chronic Dietary (all 

populations) 

NOAEL = 5 

mg/kg/day

UFA = 10X 

UFH = 10X 

FQPA SF = 1X

Chronic RfD 

= 0.05 mg/kg/day

cPAD = 0.05 mg/kg/day

Chronic toxicity/ carcinogenicity 

study in rats (MRID 00086003)

LOAEL = 25 mg/kg based on 

decreased body weights and body 

weight gains in males.

Incidental Oral

(Short- Term)

NOAEL=75 

mg/kg/day

UFA = 10X 

UFH = 10X 

FQPA SF = 1X

Residential LOC for 

MOE= 100

Developmental toxicity study in 

rabbits (MRID 41983101)

LOAEL= 200 mg/kg/day based 

on decreased body weights and 

body weight gains.

Cancer (oral, dermal, 

inhalation)

Classification: Not likely to be carcinogenic to humans.

A quantitative carcinogenic risk assessment for chlorsulfuron is not required. 

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 (interspecies). UFH = potential variation in sensitivity among members of the human 

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

Table 4.3.2. Summary of Toxicological Doses and Endpoints for Chlorsulfuron for Use in Occupational 

Human Health Risk Assessments.

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological 

Effects

Dermal exposure 

(short- and 

intermediated-term)

Oral

NOAEL = 75 

mg/kg/day

UFA = 10x

UFH =10x

Dermal 

Absorption

= 100%

Occupational LOC for 

MOE = 100

Developmental toxicity study in 

rabbits (MRID 41983101) 

LOAEL= 200 mg/kg/day based on 

decreased body weights and body 

weight gains.

Inhalation exposure 

(Short- & intermediate 

term)

Oral

NOAEL = 75 

mg/kg/day

UFA = 10x

UFH =10x

Inhalation 

Absorption

= 100%

Occupational LOC for 

MOE = 100

Developmental toxicity study in 

rabbits (MRID 41983101)

LOAEL= 200 mg/kg/day based on 

decreased body weights and body 

weight gains.

Cancer (oral, dermal, 

inhalation)

Classification: Not likely to be carcinogenic to humans.

A quantitative carcinogenic risk assessment for chlorsulfuron is not required. 

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 (interspecies). UFH = potential variation in sensitivity among members of the human 

population (intraspecies). MOE = margin of exposure. LOC = level of concern. 

4.4 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 most recent re-registration decision for chlorsulfuron, EPA 
Chlorsulfuron Human Health Risk Assessment D425536

Page 9 of 30

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. A second list of 

chemicals identified for EDSP screening was published on June 14, 20131and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website. 2

5.0 Dietary Exposure and Risk Assessment

5.1 Residue Chemistry

The existing residue chemistry database for chlorsulfuron is complete and adequate for risk 

assessment purposes. No additional residue chemistry data are required at this time. The 

qualitative nature of the residues of chlorsulfuron in plants and livestock are adequately 

understood, and adequate enforcement analytical methods are available. The HED Metabolism 

Committee determined that the residue of concern for risk assessment and tolerance enforcement 

in plant and livestock commodities is the parent only (Memos, J. Abbotts, 04/11/1995, D213534, 

and J. Abbotts, 08/09/1995, D217473). 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. Analytical reference standards for 

chlorsulfuron are currently available for chlorsulfuron and expire in December 2016 (Appendix 

C).

 

1 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of chemicals.

2 http://www.epa.gov/endo/
Chlorsulfuron Human Health Risk Assessment D425536

Page 10 of 30

5.2 Drinking Water

Screening ground water-sourced drinking water exposure estimates were generated with the 

Pesticide Root Zone Model for GroundWater (PRZM-GW; v.1.07) for use in the sulfonylurea 

(SU) dietary risk assessments. EFED initially provided coarse-screen estimates that should 

exceed the upper-bound chemical-specific EDWCs for any SU; however, for several of the SUs, 

the coarse-screen EDWCs resulted in dietary risks of concern and EFED subsequently generated 

refined-screen EDWCs for these SUs. The application inputs for the refined-screen EDWCs 

represent the maximum application rate pattern for the chemical, considering the maximum 

single application rate first, then the maximum seasonal application rate, using usage data 

provided by Biological and Economics Analysis Division (BEAD) if the labels do not provide a 

maximum seasonal rate. The modeled sorption coefficient is also chemical-specific. All other 

inputs, including the screening assumptions of stability to degradation and application every 

year, remained the same as for the coarse screen. The resulting refined-screen EDWCs from 

PRZM-GW can be used as a conservative estimate of exposure and are summarized in Table 5.2

(G. Orrick, 12-AUG-2015; D427429). 

The chronic dietary assessment for chlorsulfuron used the refined-screen post-breakthrough 

mean value of 52 μg/L (0.052 ppm). 

Table 5.2. PRZM-GW Refined-Screen EDWCs for Sulfonylureas1.

Sulfonylurea (Use)

PRZM-GW 

Scenario Max. Daily Conc. 

(μg/L)

Postbreakthrough 

Mean (μg/L)

Mean 

Breakthrough 

Time (years)

Chlorsulfuron (non-ag areas) NC cotton 78 52 5.9

Halosulfuron-methyl (fallow) NC cotton 74 53 8.1

Nicosulfuron (rights-of-way) NC cotton 39 26 6.2

Prosulfuron (corn) NC cotton 15 13 12

Rimsulfuron (commercial areas) NC cotton 105 71 6.5

Triasulfuron (rangeland) NC cotton 21 19 16

Tribenuron-methyl (corn) NC cotton 35 23 6.1

Triflusulfuron-methyl (sugar beet) FL citrus 23 20 9.5

1 The EDWCs for chlorsulfuron are in bold.

5.3 Dietary (Food + Drinking Water) Risk Assessment

HED has conducted a chronic dietary exposure and risk assessment for chlorsulfuron using 

tolerance-level residues in foods, 100% crop treated, and EDWCs provided by EFED. Exposure 

and risk estimates were obtained from the Dietary Exposure Evaluation Model using the Food 

Commodity Intake Database (DEEM-FCID; version 3.18). The model uses food consumption 

data from the 2003-2008 NHANES/WWEIA database, coupled with recipe files and residues in 

foods, to derive estimates of dietary exposure and risk. 

Generally, HED is concerned when chronic dietary exposure estimates exceed 100% of the 

cPAD. Chronic dietary risk estimates (food and drinking water) are not of concern for the 

general U.S. population or any other population subgroup (Table 5.3). The chronic exposure 

estimate is 4.5% of the cPAD for the general U.S. population and 14% of the cPAD for children 

1-2 years old, the most highly-exposed population subgroup. Because of the very conservative 

assumptions used in the analysis (tolerance-level residues, 100% crop treated, upper-bound 
Chlorsulfuron Human Health Risk Assessment D425536

Page 11 of 30

modeled drinking water estimates), actual exposure and risk are expected to be much lower than 

those shown in Table 5.3. The listings of inputs and outputs to the assessment are included in 

Appendix D. HED did not conduct an acute dietary exposure and risk assessment due to the lack 

of an appropriate endpoint for acute dietary assessment. Chlorsulfuron is classified as “not likely 

to be carcinogenic to humans”; therefore, cancer risk is not a concern.

Table 5.3. Summary of Chronic Dietary Exposure (Food and Drinking Water) and Risk for 

Chlorsulfuron1.

Population Subgroup

Chronic Dietary

Dietary Exposure (mg/kg/day) % cPAD

General U.S. Population 0.002263 4.5

All Infants (<1 year old) 0.004267 8.5

Children 1-2 years old 0.006917 14

Children 3-5 years old 0.004745 9.5

Children 6-12 years old 0.003012 6.0

Youth 13-19 years old 0.001856 3.7

Adults 20-49 years old 0.001906 3.8

Adults 50-99 years old 0.001790 3.6

Females 13-49 years old 0.001843 3.7

1 Population with the greatest exposure is in bold. Exposure and risk estimates calculated using DEEM version 3.18.

6.0 Residential (Non-Occupational) Exposure and Risk Assessment

There are no registered residential uses or occupational uses resulting in direct residential 

exposure associated with chlorsulfuron. Therefore, a quantitative residential exposure 

assessment for direct residential uses was not performed.

6.1 Spray Drift

A detailed description about HED’s spray drift policy and how to evaluate the drift potential and 

associated risks is available in Appendix F. 

6.1.1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications

The spray drift risk estimates are based on an estimated deposited residue concentration as a 

result of the screening-level agricultural application scenarios. Chlorsulfuron is used on barley, 

grasses grown for seed, oats, pastures, rangeland, rights-of-way, triticale, wheat, and industrial 

and commercial turf, and can be applied via aerial, groundboom, and hand-held equipment. The 

spray drift assessment was conducted using the registered application rate of 0.06 lb ai/acre for 

use on pastures and rangeland. The higher application rate of 0.14 lb ai/acre for use on rights-ofway and industrial turf was not assessed for spray drift because it is applied with hand-held 

equipment in these areas. The recommended drift scenario screening-level options are listed 

below: 

 Groundboom applications are based on the AgDrift® option for high boom height and 

using very fine to fine spray type using the 90th percentile results. 

 Aerial applications are based on the use of AgDrift® Tier 1 aerial option for a fine-tomedium spray type and a series of other parameters, which is described in more detail 

below (e.g., wind vector assumed to be 10 mph in a downwind direction for entire 

application/drift event).
Chlorsulfuron Human Health Risk Assessment D425536

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Dermal risk estimates have been evaluated for adults. Dermal and incidental oral risk estimates 

were evaluated for children (1 to < 2 years old). The total applicable LOC is 100 so MOEs < 

100 would be of concern. Children’s (1 < 2 years old) dermal and incidental oral risk estimates 

and adult dermal risk estimates from exposure to chlorsulfuron related to spray drift result in no 

risks of concern at the field edge for either groundboom or for aerial applications. Results are 

presented below in Tables 6.1.1 and 6.1.2.

Table 6.1.1. Adult Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for Chlorsulfuron

for the Dermal Route of Exposure.

Application 

Equipment

Spray Type/ 

Nozzle 

Configuration

Application 

Rate (lb ai/A)

Estimated or Adjusted 

TTR (ug/cm2)

At Edge

Dermal MOE

Pastures, Rangeland

Aerial Fine to Medium

0.06 0.006669

13,000

Groundboom High Boom Very 

fine to Fine 18,000

Table 6.1.2. Children (1 < 2 years old) Risk Estimates (MOEs) Related to Indirect Exposure to Spray 

Drift for Chlorsulfuron for Combined Route of Exposure.

Application 

Equipment

Spray Type/ 

Nozzle 

Configuration 

Application 

Rate (lb ai/A)

Estimated or 

Adjusted TTRt

(ug/cm2)

At Edge 

Combined MOE1

Pastures, Rangeland

Aerial Fine to Medium

0.06 0.006669

 6,400

Groundboom High Boom Very 

fine to Fine 8,800 

1. Dermal and incidental oral risks were combined for children 1 to < 2 years old.

6.2 Residential Bystander Post-Application Inhalation Exposure

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

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

Scientific Advisory Panel (FIFRA 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 has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the Agency will use this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for chlorsulfuron.

7.0 Aggregate Exposure and Risk Assessment

The Food Quality Protection Act of 1996 directs EPA to assess aggregate exposure to pesticide 

chemical residues, including all anticipated dietary exposures and all other exposures for which 

there is reliable information. In the case of chlorsulfuron, aggregate exposure and risk estimates 

are equivalent to the dietary exposure and risk estimates in Section 5.3, and are not of concern. 
Chlorsulfuron Human Health Risk Assessment D425536

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8.0 Cumulative Exposure/Risk Characterization

In 2015, EPA’s Office of Pesticide Programs released a guidance document entitled, Pesticide 

Cumulative Risk Assessment: Framework for Screening Analysis 

(http://www.epa.gov/oppfead1/cb/csb_page/updates/2015/framework-for-screeninganalysis.html). This document provides guidance on how to screen groups of pesticides for 

cumulative evaluation using a two-step approach beginning with the evaluation of available 

toxicological information and if necessary, followed by a risk-based screening approach. This 

framework supplements the existing guidance documents for establishing common mechanism 

groups (CMGs)3and conducting cumulative risk assessments (CRA)4. The Agency has utilized 

this framework to evaluate the SUs of which chlorsulfuron is a member (J. D’Agostino; 

D428798; 09-SEP-2015). Although the SUs share some chemical and toxicological 

characteristics, the toxicological database does not support a testable hypothesis for a common 

mechanism of action. No further mechanistic data are required and no further cumulative 

evaluation is necessary. 

9.0 Occupational Exposure/Risk Characterization

Based on the registered use pattern (summarized in Table 3.2), there is a potential for exposure to 

chlorsulfuron in occupational settings from handling chlorsulfuron products during the 

application process (i.e., mixer/loaders, applicators, and mixer/loader/applicators) and from 

entering treated areas after application.

9.1 Occupational Handler Exposure/Risk Estimates

Based on current labeling, types of equipment and techniques that can potentially be used, 

occupational exposure associated with handler activities (i.e., mixing, loading, and applying) is 

expected from the registered uses on barley, grasses grown for seed, oats, pastures, rangeland, 

rights-of-way, triticale, wheat, and industrial and commercial turf. The quantitative 

exposure/risk assessment developed for occupational handlers is based on the scenarios listed in 

Table 9.1.1. Based on the use patterns (i.e., 1 application per season) and resistance management 

practices, occupational exposure from the registered uses is expected to be short-term (1-30 

days) and intermediate-term (1-6 months) in duration. Long-term exposures (greater than 6 

months) are not anticipated. The registered labels require handlers to wear baseline attire and 

chemical-resistant gloves.

The requirement for a dislodgeable foliar residue (DFR) study has been waived at this time for 

chlorsulfuron. For additional details, see Appendix G.

Occupational Handler Exposure Data and Assumptions

Application Rate: The highest application rate of the registered uses is listed in Table 3.2.

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. 

Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, 

 

3 Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common Mechanism of Toxicity

(USEPA, 1999)

4 Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity

(USEPA, 2002)
Chlorsulfuron Human Health Risk Assessment D425536

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include Pesticide Handler's Exposure Database (PHED) 1.1, the Agricultural Handler Exposure 

Task Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF) 

database, or other registrant-submitted occupational exposure studies. Some of these data are 

proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The 

standard values recommended for use in predicting handler exposure that are used in this 

assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit 

Exposure Surrogate Reference Table5”, which, along with additional information on HED policy 

on use of surrogate data, including descriptions of the various sources, can be found at the 

Agency website6. 

Area Treated or Amount Handled: The area treated or amount handled is based on HED 

ExpoSAC Policy No. 9.1. Refer to Table 9.1.1. for these assumptions for each scenario.

Risk Estimate Equations: The algorithms used to estimate non-cancer exposure and dose for 

occupational handlers can be found in Appendix E.

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

The short- and intermediate-term dermal and inhalation risk estimates for the occupational 

handlers are greater than HED’s LOC (i.e., MOEs ≥ 100) at baseline for all scenarios, with 

MOEs ranging from 360 to 40,000. Table 9.1.1 provides the worst-case scenarios (e.g., highest 

application rates and exposure scenarios) for the registered uses for chlorsulfuron.

The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for 

human flaggers where appropriate, agricultural aviation has changed dramatically over the past 

two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily 

from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide 

applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent 

(2012) NAAA survey. The Agency will continue to monitor all available information sources to 

best assess and characterize the exposure potential for human flaggers in agricultural aerial 

applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for 

exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeved shirt, long pants, shoes, 

and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, 

pilots are not required to wear protective gloves for the duration of the application. With this 

level of protection, there are no risk estimates of concern for applicators.

 

5 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

6 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Chlorsulfuron Human Health Risk Assessment D425536

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Table 9.1.1. Occupational Short-term/Intermediate-term Handler Exposure and Risk Estimates for 

Chlorsulfuron.

Exposure 

Scenario

Crop or 

Target1

Baseline 

Dermal 

Unit 

Exposure2

Baseline 

Inhalation 

Unit 

Exposure2

Maximum

Application 

Rate3

Area 

Treated 

or 

Amount 

Handled 

Daily4

Baseline Dermal Baseline Inhalation Total

Dose5 MOE6 Dose5 MOE6 MOE7

μg/lb ai μg/lb ai

lb ai/A

(unless 

otherwise

noted)

Acres

(unless 

otherwise 

noted)

mg/kg/day LOC = 

100 mg/kg/day LOC = 100

LOC =

100

Mixer/Loader

M/L WDG/DF 

for Aerial 

Application 

Pastures, 

Rangeland 227 8.96 0.06 1,200 acres

0.204 370 0.00806 9,300 360

M/L WDG/DF 

for Groundboom 

Application

Pastures, 

Rangeland 227 8.96 0.06 200 acres 0.034 2,200 0.00135 56,000 2,100

M/L

WDG/DF for 

MechanicallyPressurized

Handgun 

Application

Rights-ofway (e.g., 

utilities, 

railroad, 

roadways)

227 8.96 0.0014 lb 

ai/gallon

1,000 

gallons 0.00398 19,000 0.000156 480,000 18,000

Applicator

Applying Sprays 

for Aerial 

Application

Pastures, 

Rangeland

2.08

(EC) 0.0049 0.06 1,200 acres

0.00188 40,000 0.00000441 17,000,000 40,000

Applying Sprays 

for Groundboom 

Application

Pastures, 

Rangeland 78.6 0.34 0.06 200 acres 0.0118 6,400 0.000051 1,500,000 6,400

Applying Sprays 

for 

MechanicallyPressurized 

Handgun 

Application

Rights-ofway (e.g., 

utilities, 

railroad, 

roadways)

1,300 3.9 0.0014 lb 

ai/gallon

1,000 

gallons 0.0228 3,300 0.0000683 1,100,000 3,300

Flagger for 

Aerial 

Application for 

Sprays

Pastures, 

Rangeland 11 0.35 0.06 350 acres 0.00289 26,000 0.0000919 820,000 25,000

Mixer/Loader/Applicator

M/L/A 

WDG/DF for 

Backpack 

Application

Rights-ofway (e.g., 

utilities, 

railroad, 

roadways)

8,260 2.58 0.0014 lb 

ai/gallon

40 

gallons 0.00579 13,000 0.0000018 42,000,000 13,000

M/L/A Liquids 

with Backpack 

Rights-ofway (e.g., 

utilities, 

railroad, 

roadways)

8,260 2.58 0.0014 lb 

ai/gallon

40 

gallons 0.00579 13,000 0.0000018 42,000,000 13,000

1 The worst-case scenarios for the registered uses for chlorsulfuron are listed in this table. 

2 “Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”; Level of mitigation = Baseline except for aerial 

applicator which includes engineering controls (EC).

3 Based on the currently registered labels (See Table 3.2).

4 Exposure Science Advisory Council Policy #9.1.

5 Dermal Dose = Dermal Unit Exposure (μg/lb ai) ) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated or 

Amount Handled Daily (A or gal/day) x DAF (%) ÷ BW (80 kg). Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor 

(0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 kg).

6 Dermal MOE = Dermal NOAEL (75 mg/kg/day) ÷ Dermal Dose (mg/kg/day). Inhalation MOE = Inhalation NOAEL (75 mg/kg/day) ÷ 

Inhalation Dose (mg/kg/day).

7 Total MOE = NOAEL (75 mg/kg/day) ÷ Dermal Dose + Inhalation Dose.
Chlorsulfuron Human Health Risk Assessment D425536

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9.2 Occupational Post-Application Exposure/Risk Estimates

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

Occupational post-application exposure is expected based on the registered agricultural products 

for chlorsulfuron. Occupational post-application exposure from rights-of-way and industrial turf 

uses were not assessed because an occupational worker would not re-enter these areas to perform 

any job functions after chlorsulfuron is applied. The occupational post-application exposure 

scenarios associated with the highest uses for chlorsulfuron are summarized in Table 9.2. All 

scenarios resulted in MOEs greater than the LOC of 100 (ranging from 2,300 to 190,000) on day 

0 (12 hours after application); and therefore, are not of concern to HED. Table 9.2. provides the 

worst-case scenarios (highest exposure scenario based on the application rates) for the registered 

uses for chlorsulfuron.

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

Crop/Site Activities

Transfer 

Coefficient 

(cm2/hr)

Application Rate

(lb ai/A) DFR1 Dermal Dose (mg/kg/day)2 MOE3

Short- and Intermediate-term

Wheat Hand Weeding 70 0.02 0.06 0.0004 190,000

Wheat Scouting 1,100 0.02 0.06 0.006 12,000

Pastures, 

Rangeland Scouting 1,100 0.06 0.17 0.019 4,100

Pastures,

Rangeland Irrigation 1,900 0.06 0.17 0.032 2,300

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

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

3 MOE = POD (mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR (μg/cm2) × TC × 0.001 mg/μg × 8 hrs/day × dermal 

absorption factor (100 %)]  BW (80 kg).

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application 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 FIFRA 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 

has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration

Review, the Agency will use this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for chlorsulfuron.
Chlorsulfuron Human Health Risk Assessment D425536

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In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the agency's risk assessments.

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

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

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

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

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

inhalation exposure scenarios.

Restricted Entry Interval

Chlorsulfuron is classified as Toxicity Category III or IV based upon data for acute dermal 

toxicity, acute inhalation toxicity, primary skin irritation, and primary eye irritation. Upon 

review of the criteria for the active ingredient only, it appears that chlorsulfuron is consistent 

with the criteria in PRN 95-3 that allow for a 4-hour REI. Note: The PR Notice also includes 

similar criteria for the end-use product. These criteria have not been evaluated by HED. Based 

solely on the active ingredient criteria, HED would recommend for reduction of the REI for 

chlorsulfuron.

10.0 Public Health, Pesticide Epidemiology, and Human Incidence Data

The OPP Incident Data System (IDS) was consulted for pesticide incident data on the active 

ingredient chlorsulfuron. HED notes that chlorsulfuron is not included in the Agricultural Health 

Study (AHS). At the time of the scoping document for chlorsulfuron (M. Hawkins et al., 6-

DEC-2012; D403355), there was a low frequency and severity of incident cases reported; 

therefore, further investigation was not warranted at that time (S. Recore, 31-JUL-2012; 

D403831). The Agency has continued to monitor the incident information, but a concern has not 

been triggered, and therefore, additional analyses have not been included in this risk assessment.
Chlorsulfuron Human Health Risk Assessment D425536

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11.0 References

Table 11.0 HED Memoranda Relevant to Registration Review.

Authors Barcode Date Title

M. Hawkins et 

al. D403355 12/6/2012 Chlorsulfuron: Registration Review Scoping Document for Human Health Assessments.

J. Van Alstine TXR #: 

0056439 2/8/2013

Chlorsulfuron: Summary of Hazard and Science Policy 

Council (HASPOC) Meeting of August 9, 2012: 

Recommendations on the need for the inhalation, dermal, acute 

and subchronic neurotoxicity studies.

K. Rury TXR #: 

0056723 8/6/2013

Sulfonylureas: Summary of Hazard and Science Policy 

Council (HASPOC) Meeting on July 18, 2013: 

Recommendations on Data Requirement for Immunotoxicity 

Studies for Sulfonylurea Pesticides.

J. Abbotts D213534 04/11/1995

Results of the HED Metabolism Committee Meeting Held on 

4/4/95: Chlorsulfuron Residue to be Regulated. CBRS No. 

15318, DP Barcode No. D213534, No MRID No.

J. Abbotts D217473 08/09/1995

Chlorsulfuron (118601), Reregistration Case No. 0631. 

Decision of the HED Metabolism Committee, Residues to be 

Regulated in Animal Commodities. CBRS No. 15880, DP 

Barcode No. 217473, No MRID No.

F. Fort et al. D266070 07/18/02

PP#: 0F06120. Chlorsulfuron in/on Pasture Grasses. Health 

Effects Division (HED) Risk Assessment. PC Code: 118601. 

DP Barcode: D266070 Case #: 292904. Submission #: 

S613409

S. Recore D403831 7/31/2012 Chlorsulfuron: Review of Human Incidents

G. Orrick D427429 08/12/2015 Drinking Water Exposure Assessment for the Registration 

Review of 22 Sulfonylurea Herbicides.

J. D’Agostino D428798 09/09/2015

Sulfonylureas: Screening Analysis of Toxicological Profiles to 

Consider Whether a Candidate Common Mechanism Group 

Can Be Established.
Chlorsulfuron Human Health Risk Assessment D425536

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Appendix A. Toxicology Profile Tables

A.1. Toxicology Data Requirements

Table A.1. Toxicology Data Requirements for Chlorsulfuron

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

CR

yes

yes

waived1

-

waived1

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

-

-

waived1

waived1

-

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

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

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

yes

no

yes

yes

-

Waived1

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

this time.
Chlorsulfuron Human Health Risk Assessment D425536

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A.2. Toxicity Profiles

Table A.2.1. Acute Toxicity of Chlorsulfuron Technical

Guideline No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral 00031406 Rat LD50 = 5.5 g/kg (M)

Rat LD50 = 6.3 g/kg (F)

IV

870.1200 Acute Dermal 00083956 Rabbit LD50 = 3400 mg/kg III

870.1300 Acute Inhalation 00086825 Rat LC50 = 5.9 mg/L IV

870.2400 Primary Eye 

Irritation

46449005 Not an eye irritant IV

870.2500 Primary Skin 

Irritation

46449006 Slightly irritating to skin IV

870.2600 Dermal 

Sensitization 46449007 Not a skin sensitizer NA

Table A.2.2. Subchronic, Chronic and Other Toxicity Profile for Chlorsulfuron

Guideline No./

Study Type

MRID No. (year)/ Classification 

/Doses

Results

870.3100 [§82-1 (a)

Subchronic oral (90 days)

-Rats

00031418 [1980]

Unacceptable/Guideline

(0, 100, 500, 2500 ppm) 

M: 0, 6.5, 33.7, 161.1 mg/kg/day

F: 0, 8.1, 40.4, 216.6 mg/kg/day

NOAEL: 161.1 mg/kg/day [2500 ppm; HDT]. No 

effects were observed. Dosing inadequate; well below 

the limit dose

870.3150 [§82-1 (b)]

Subchronic oral (6 months)

-Dogs

00031420 [1980]

Acceptable/non-guideline

(0, 100, 500, 2500 ppm) 

0, 3.7, 18.5, 82.3 mg/kg/day (M/F)

NOAEL: 82.3 mg/kg/day

LOAEL >82.3 mg/kg/day

870.3100 [§82-1 (a)]

Subchronic oral (90 days)

-Mice

00031421 [1980]

Acceptable/non-guideline

(0, 500, 2500, 5000, 7500 ppm) 

M: 0, 150, 783, 1557, 2130 mg/kg/day

F: 0, 220, 1214, 2134, 3176 mg/kg/day

NOAEL: 1557 mg/kg/day

LOAEL: 2130 mg/kg/day, based on an increased 

incidence of retinal dysplasia and adrenal capsular cell 

proliferation.

870.4100[§83-1b] 

Chronic feeding study

-Beagle dogs

41862601(1991) 

Acceptable/Guideline

(0, 100, 2000, 7500 ppm)

M: 0, 3.5, 65.6, 215 mg/kg/day

F: 0, 3.5, 60.6, 254.5 mg/kg/day 

NOAEL: 60.6 mg/kg/day 

LOAEL: 215 mg/kg/day, based on decreased body 

weight gain, erythrocyte counts, and hemoglobin 

levels

870.4300 [§83-5]

Chronic feeding/

carcinogenicity study

-CD® rats 

00086003 (1981)

Acceptable/non-guideline

(0, 100, 500, 2500 ppm) 

M/F: 0, 5, 25, and 125 mg/kg/day 

(by a standard conversion factor)

NOAEL: 50 ppm [5 mg/kg/day]

LOAEL: 500 ppm [25 mg/kg/day], based on 

decreased body weight and body weight gain in males

There was no treatment-related increase in tumor 

incidence in either sex. 

870.4200 [§83-2]

Carcinogenicity study

-CD-1 mice

00090030 [1981]

Acceptable/Guideline

(0, 100, 500, 5000 ppm) 

M/F: 0, 15, 108, 750 mg/kg/day

(by a standard conversion factor)

NOAEL = 500 ppm [108 mg/kg/day]

LOAEL: 5000 ppm [750 mg/kg/day], based on 

decreased body weight and body-weight gain.

There was no treatment-related increase in tumor 

incidence in either sex. 

870.3700 [§83-3a]

Developmental Toxicity 

-Crl:CD®(SD)BR rats

41976406 (1991)

Acceptable/Guideline

0, 55, 165, 500, 1500 mg/kg/day

Maternal NOAEL: 165 mg/kg/day

Maternal LOAEL: 500 mg/kg/day, based on clinical 

signs [vaginal discharge with associated alopecia. At 
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Table A.2.2. Subchronic, Chronic and Other Toxicity Profile for Chlorsulfuron

Guideline No./

Study Type

MRID No. (year)/ Classification 

/Doses

Results

HDT, there were two deaths [GD 12 and 18], and 

additional clinical signs [swollen limbs and faces].

Developmental NOAEL: 500 mg/kg/day 

Developmental LOAEL: 1500 mg/kg/day, based on 

decreased fetal body weight. 

870.3700 [§83-3b]

Developmental Study 

-Hra:(NZW)SPF Rabbits

41983101 (1991)

Acceptable/Guideline

0, 25, 75, 200, 400 mg/kg/day (original 

study); 400 and 1000 mg/kg/day 

(supplemental study)

Maternal NOAEL: 75 mg/kg/day

Maternal LOAEL: 200 mg/kg/day, based on decreased 

body weights and body-weight gains. 

At 400 mg/kg/day, there were 8/20 deaths and 6 

abortions.

Developmental NOAEL: 200 mg/kg/day 

Developmental LOAEL: 400 mg/kg/day, based on a 

slight increase in visceral malformations and 

decreased fetal body weight.

870.3800 [§83-4]

3-Gen Reproduction 

Toxicity

-CD® Rats

00086003 (1981)

Unacceptable/non-guideline

(0, 100, 500, 2500 ppm)

0, 5, 25, 125 mg/kg/day

Parental NOEL: 2500 ppm [125 mg/kg/day]

Parental LOEL: >2500 ppm [125 mg/kg/day], no 

effects observed.

Reproductive NOEL: 100 ppm [5 mg/kg/day]

Reproductive LOEL: 500 ppm [25 mg/kg/day], based 

on decreased female fertility.

Offspring NOEL 2500 ppm [125 mg/kg/day]

Offspring LOEL >2500 ppm, no effects observed.

870.3800

2-Gen Reproduction 

-Crl:CD® (SD) Rats

46493201 (2005)

Acceptable/Guideline

(0, 100, 500, 2500, 7500 ppm)

M: 0, 6, 30, 151, 456 mg/kg/day

F: 0, 7, 39, 188, 591 mg/kg/day 

Parental NOAEL: 2500 ppm (151/188 mg/kg/day; 

M/F)

Parental LOAEL: 7500 ppm (456/591 mg/kg/day; 

M/F) based on decreased body weight, weight gain 

and food consumption.

Reproductive NOAEL: 7500 ppm (456/498 

mg/kg/day) (HDT)

Offspring NOAEL; 7500 ppm ppm (456/498 

mg/kg/day) (HDT)

870.5100

Gene mutation

S. typhimurium/E.coli

47179902 (2007)

10-5000 μg/plate, +/- S9

Acceptable/Guideline

Negative, (+/-) S9 mix

870.5100

Ames, reverse mutation

S. typhimurium

00031425

6-30 μg/plate, +/- S9

Unacceptable/upgradeable

Negative, (+/-) S9 mix

870.5300

Mammalian cells in

culture - gene mutation

[HGPRT]

00083943

0.028-2.8 mM, +/- S9

Unacceptable/upgradeable

Negative

870.5395

Mouse bone marrow 

micronucleus 

47179903 (2003)

0, 500, 1000, 2000 mg/kg, gavage

Acceptable/Guideline

Negative

870.5385. 

in vitro cytogenetics assay; 

chromosome aberration 

[CHO-WBI cells]

00088755

16.7-5000 μg/mL, +/- S9

Acceptable

Negative

870.5450. 

Dominant lethal assay

00083944

100, 500, 5000 ppm

Unacceptable

Negative

870.5450 00090008

0.0002-2.0 mg/mL

Negative
Chlorsulfuron Human Health Risk Assessment D425536

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Table A.2.2. Subchronic, Chronic and Other Toxicity Profile for Chlorsulfuron

Guideline No./

Study Type

MRID No. (year)/ Classification 

/Doses

Results

Unscheduled DNA 

synthesis primary rat 

hepatocyte assay

Confirmatory: 0.0004-4.0 mg/mL

Unacceptable/upgradeable

870.7485[§85-1]

Metabolism

42540701 [1989]

Acceptable/guideline

Chlorsulfuron is rapidly absorbed, metabolized, and 

eliminated following oral exposure [single low, single 

high, and repeated low dosing regimens] to rats. There 

were no remarkable sex-, dose-, or treatment-related 

differences in the absorption, distribution, and 

excretion of chlorsulfuron in rats. The major routes of 

elimination are the urine [58%-72%] and feces [20%-

35%]. Small amounts [0.1%-0.2% of administered 

dose] were found in the tissues 3 days after dosing. 

The highest concentrations were in the liver and whole 

blood in both sexes. A major and a minor metabolic 

pathway were identified. 
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Appendix B. Chemical Identity

TABLE B.1. Chlorsulfuron Nomenclature.

Compound Chemical Structure

Common name Chlorsulfuron

IUPAC name 1-(2-chlorophenylsulfonyl)-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)urea

CAS name 2-chloro-N-[[(4-methoxy-6-methyl-1,3,5-triazin-2-

yl)amino]carbonyl]benzenesulfonamide

CAS # 64902-72-3

TABLE B.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
Chlorsulfuron Human Health Risk Assessment D425536

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Appendix C. Analytical Standards for Chlorsulfuron

Analytical reference standards for chlorsulfuron are currently available in EPA’s National 

Pesticide Standards Repository (NPSR) and have an expiration date of 12/19/2016 (email 

communication between G. Verdin and J. Van Alstine, 05/07/2015). The registrant is required to 

maintain reasonable amounts of the reference standards for chlorsulfuron in the NPSR as long as 

tolerances remain published in 40 CFR §180.405. When necessary, new reference standards, or 

updated certificates of analysis (COAs), should be sent to the Analytical Chemistry Branch 

(ACB), which is located at Fort Meade, MD. It should be sent to the attention of either Theresa 

Cole or Thuy Nguyen at the address listed below, along with a letter of transmittal. Please note 

that the full 9-digit ZIP Code is required, or the mail will be returned to the registrant. 

USEPA

National Pesticide Standards Repository

Analytical Chemistry Branch/BEAD/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

The letter of transmittal should include the assay of the standard, name of the analytical method 

used, a statement of principal impurities, purification procedures employed, storage 

requirements, and special precautions for safe handling. Replacement of standards, or updated 

certificates of analysis, may be required periodically if supplies are exhausted, if the standards 

expire, or if decomposition occurs during storage. Material Safety Data Sheets (MSDSs) must 

accompany all analytical standards as specified by the Occupational Safety and Health 

Administration (OSHA) in 29CFR §1910.1200. 
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Appendix D. Dietary Exposure/Risk Modeling Input and Output Files

DEEM-FCID Chronic Inputs File

Filename: C:\Users\jlangsda\Documents\Chemicals\SUs\Chlorsulfuron\Dietary 

Assessment\Chlorsulfuron_Chronic.r08

Chemical: Chlorsulfuron

RfD(Chronic): .05 mg/kg bw/day NOEL(Chronic): 5 mg/kg bw/day

RfD(Acute): 0 mg/kg bw/day NOEL(Acute): 0 mg/kg bw/day

Date created/last modified: 05-20-2015/15:56:32 Program ver. 3.16, 03-08-d

Comment: UFa=10x; UFh=10x; FQPA SF=1x

-----------------------------------------------------------------------------------

 EPA Crop Def Res Adj.Factors Comment

 Code Grp Commodity Name (ppm) #1 #2 

---------- ---- ------------------------------- ---------- ------ ------ -------

1500025000 15 Barley, pearled barley 0.100000 1.000 1.000 

1500025001 15 Barley, pearled barley-babyfood 0.100000 1.000 1.000 

1500026000 15 Barley, flour 0.100000 1.000 1.000 

1500026001 15 Barley, flour-babyfood 0.100000 1.000 1.000 

1500027000 15 Barley, bran 0.100000 1.000 1.000 

1500231000 15 Oat, bran 0.100000 1.000 1.000 

1500232000 15 Oat, flour 0.100000 1.000 1.000 

1500232001 15 Oat, flour-babyfood 0.100000 1.000 1.000 

1500233000 15 Oat, groats/rolled oats 0.100000 1.000 1.000 

1500233001 15 Oat, groats/rolled oats-babyfood 0.100000 1.000 1.000 

1500381000 15 Triticale, flour 0.100000 1.000 1.000 

1500381001 15 Triticale, flour-babyfood 0.100000 1.000 1.000 

1500401000 15 Wheat, grain 0.100000 1.000 1.000 

1500401001 15 Wheat, grain-babyfood 0.100000 1.000 1.000 

1500402000 15 Wheat, flour 0.100000 1.000 1.000 

1500402001 15 Wheat, flour-babyfood 0.100000 1.000 1.000 

1500403000 15 Wheat, germ 0.100000 1.000 1.000 

1500404000 15 Wheat, bran 0.100000 1.000 1.000 

3100044000 31 Beef, meat 0.300000 1.000 1.000 

3100044001 31 Beef, meat-babyfood 0.300000 1.000 1.000 

3100045000 31 Beef, meat, dried 0.300000 1.920 1.000 

3100046000 31 Beef, meat byproducts 0.300000 1.000 1.000 

3100046001 31 Beef, meat byproducts-babyfood 0.300000 1.000 1.000 

3100047000 31 Beef, fat 0.300000 1.000 1.000 

3100047001 31 Beef, fat-babyfood 0.300000 1.000 1.000 

3100048000 31 Beef, kidney 0.300000 1.000 1.000 

3100049000 31 Beef, liver 0.300000 1.000 1.000 

3100049001 31 Beef, liver-babyfood 0.300000 1.000 1.000 

3200169000 32 Goat, meat 0.300000 1.000 1.000 

3200170000 32 Goat, meat byproducts 0.300000 1.000 1.000 

3200171000 32 Goat, fat 0.300000 1.000 1.000 

3200172000 32 Goat, kidney 0.300000 1.000 1.000 

3200173000 32 Goat, liver 0.300000 1.000 1.000 

3300189000 33 Horse, meat 0.300000 1.000 1.000 

3400290000 34 Pork, meat 0.300000 1.000 1.000 

3400290001 34 Pork, meat-babyfood 0.300000 1.000 1.000 

3400291000 34 Pork, skin 0.300000 1.000 1.000 

3400292000 34 Pork, meat byproducts 0.300000 1.000 1.000 

3400292001 34 Pork, meat byproducts-babyfood 0.300000 1.000 1.000 

3400293000 34 Pork, fat 0.300000 1.000 1.000 

3400293001 34 Pork, fat-babyfood 0.300000 1.000 1.000 

3400294000 34 Pork, kidney 0.300000 1.000 1.000 

3400295000 34 Pork, liver 0.300000 1.000 1.000 

3500339000 35 Sheep, meat 0.300000 1.000 1.000 

3500339001 35 Sheep, meat-babyfood 0.300000 1.000 1.000 

3500340000 35 Sheep, meat byproducts 0.300000 1.000 1.000 

3500341000 35 Sheep, fat 0.300000 1.000 1.000 

3500341001 35 Sheep, fat-babyfood 0.300000 1.000 1.000 

3500342000 35 Sheep, kidney 0.300000 1.000 1.000 

3500343000 35 Sheep, liver 0.300000 1.000 1.000 

3600222000 36 Milk, fat 0.100000 1.000 1.000 

3600222001 36 Milk, fat-baby food/infant formu 0.100000 1.000 1.000 

3600223000 36 Milk, nonfat solids 0.100000 1.000 1.000 

3600223001 36 Milk, nonfat solids-baby food/in 0.100000 1.000 1.000 

3600224000 36 Milk, water 0.100000 1.000 1.000 
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3600224001 36 Milk, water-babyfood/infant form 0.100000 1.000 1.000 

3600225001 36 Milk, sugar (lactose)-baby food/ 0.100000 1.000 1.000 

3800221000 38 Meat, game 0.100000 1.000 1.000 

3900312000 39 Rabbit, meat 0.100000 1.000 1.000 

8601000000 86A Water, direct, all sources 0.052000 1.000 1.000 

8602000000 86B Water, indirect, all sources 0.052000 1.000 1.000 

DEEM-FCID Chronic Results File

U.S. EPA Ver. 3.16, 03-08-d

DEEM-FCID Chronic analysis for CHLORSULFURON NHANES 2003-2008 2-day

Residue file name: C:\Users\jlangsda\Documents\Chemicals\SUs\Chlorsulfuron\Dietary 

Assessment\Chlorsulfuron_Chronic.r08

 Adjustment factor #2 used.

Analysis Date 05-20-2015/15:57:47 Residue file dated: 05-20-2015/15:56:32

Reference dose (RfD, Chronic) = .05 mg/kg bw/day

COMMENT 1: UFa=10x; UFh=10x; FQPA SF=1x

===============================================================================

 Total exposure by population subgroup

-------------------------------------------------------------------------------

 Total Exposure

 -----------------------------------

 Population mg/kg Percent of 

 Subgroup body wt/day Rfd 

-------------------------------------- ------------- ----------------

Total US Population 0.002263 4.5%

Hispanic 0.002423 4.8%

Non-Hisp-White 0.002281 4.6%

Non-Hisp-Black 0.001903 3.8%

Non-Hisp-Other 0.002471 4.9%

Nursing Infants 0.001499 3.0%

Non-Nursing Infants 0.005503 11.0%

Female 13+ PREG 0.001955 3.9%

Children 1-6 0.005399 10.8%

Children 7-12 0.002830 5.7%

Male 13-19 0.001972 3.9%

Female 13-19/NP 0.001744 3.5%

Male 20+ 0.001878 3.8%

Female 20+/NP 0.001835 3.7%

Seniors 55+ 0.001770 3.5%

All Infants 0.004267 8.5%

Female 13-50 0.001840 3.7%

Children 1-2 0.006917 13.8%

Children 3-5 0.004745 9.5%

Children 6-12 0.003012 6.0%

Youth 13-19 0.001856 3.7%

Adults 20-49 0.001906 3.8%

Adults 50-99 0.001790 3.6%

Female 13-49 0.001843 3.7%

-------------------------------------------------------------------------------
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Appendix E. Occupational Non-cancer Algorithms

Occupational Non-Cancer Handler Algorithms

Potential daily exposures for occupational handlers are calculated using the following formulas:

E=UE * AR * A * 0.001 mg/ug

where:

E = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),

AR = maximum application rate according to proposed label (lb ai A or lb ai/gal), and

A = area treated or amount handled (e.g., A/day, gal/day).

The daily doses are calculated using the following formula:

ADD= 

E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = exposure (mg ai/day),

AF = absorption factor (dermal and/or inhalation), and

BW = body weight (kg).

Margin of Exposure: Non-cancer risk estimates for each application handler scenario are 

calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to 

the daily dose of concern. The daily dermal and inhalation dose received by occupational 

handlers are compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational 

handlers for each exposure route. All MOE values are calculated using the following formula:

MOE= 

POD

ADD

where:

MOE = margin of exposure: value used by HED to represent risk estimates (unitless),

POD = point of departure (mg/kg/day), and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).
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Occupational Non-Cancer Post-application Algorithms

Potential daily exposures for occupational post-application workers are calculated using the 

following formulas:

DFRt=AR * F* (1-D)t* (4.54E8

ug

lb) * (2.47E-8

A

cm2

)

where:

DFRt = dislodgeable foliage residue on day "t" (μg/cm2),

AR = application rate (lb ai/acre),

F = fraction of ai retained on foliage or 25% (unitless),

D = fraction of residue that dissipates daily or 10% (unitless), and

t = number of days after application day (days).

E=TC * DFR t* ET * 0.001

mg

ug

where:

E = exposure (mg ai/day),

TC = transfer coefficient (cm2/hr),

DFRt = dislodgeable foliar residue on day “t” (μg/cm2), and

ET = exposure time (hours/day).

The daily doses are calculated using the following formula:

ADD= 

E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = exposure (mg ai/day),

AF = absorption factor (dermal and/or inhalation), and

BW = body weight (kg).

Margin of Exposure: Non-cancer risk estimates for each scenario are calculated using a Margin 

of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. 

The daily dermal dose received by occupational post-application workers is compared to the 

appropriate POD (i.e., NOAEL) to assess the risk to occupational post-application workers. All 

MOE values are calculated using the following formula:

MOE= 

POD

ADD

where:

MOE = margin of exposure: value used by HED to represent risk estimates (unitless),

POD = point of departure (mg/kg/day), and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).
Chlorsulfuron Human Health Risk Assessment D425536

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Appendix F. Spray Drift Detailed Description

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to exposures (e.g., children playing on 

lawns where residues have deposited next to treated fields). The potential risk estimates from 

these residues can be calculated using drift modeling coupled with methods employed for 

residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment include 

assessing exposures for children (1 to 2 years old) and adults who have contact with turf where 

residues are assumed to have deposited via spray drift thus resulting in an exposure scenario. 

Aside from the predicted residues available for transfer, the routes of exposure and assessment 

methodology is analogous to how exposures to turf products are considered in risk assessment. 

In order to evaluate the drift potential and associated risks, an approach based on drift modeling 

coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, 

a residential turf assessment based on exposure to deposited residues has been completed to 

address drift from the agricultural applications of chlorsulfuron. In the spray drift scenario, the 

deposited residue value was determined based on the amount of spray drift that may occur at 

varying distances from the edge of the treated field using the AgDrift® (v2.1.1) model. 

Exposures were considered for 50 feet wide lawns where the nearest side of the property was 

directly adjoining the treated field (at field edge) and at varied distances up to 300 feet 

downwind of a treated field. Once the deposited residue values were determined, the remainder 

of the spray drift assessment was based on the algorithms and input values specified in the 

recently revised (2012) Standard Operating Procedures For Residential Risk Assessment 

(SOPs). 

 

A screening approach was developed for situations where specific label guidance for 

application parameters is not available.7,8 AgDrift® is appropriate for use only when applications 

are made by aircraft, airblast sprayers, and groundboom sprayers. When AgDrift® was 

developed, a series of screening values (i.e., the Tier 1 option) were incorporated into the model 

and represent each equipment type and use under varied conditions. The screening options 

specifically recommended in this methodology were selected because they are plausible and 

represent a reasonable upper bound level of drift for common application methods in agriculture. 

In all cases, each scenario is to be evaluated unless it is not plausible based on the anticipated use 

pattern (e.g., herbicides are not typically applied to tree canopies) or specific label prohibitions 

(e.g., aerial applications are not allowed). Section 6.1.1 provides the screening level drift related 

risk estimates. These drift estimates represent plausible options based on the available pesticide 

labels. 

 

7http://www.agdrift.com/ 

8 Note that for many cases the scenarios outlined in the screening approach represent actual use practice so risk assessors should 

be aware and characterize these appropriately.
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Appendix G. DFR Data Waiver Rationale

Dislodgeable Foliar Residue (DFR): 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. HED developed a waiver policy for 

DFR studies. The MOEs from the assessment, using default values are evaluated. If those are 2 

times higher than the LOC the DFR studies can be waived. 

Since the highest estimated occupational post-application exposure using default DFR values for 

chlorsulfuron is minimal in comparison to the level of concern (i.e., the calculated MOE is 

greater than 2 times higher than the level of concern, MOE = 2,300 compared to the LOC of 

100); EPA is waiving the 40CFR DFR data requirement. In this instance, it is unlikely that 

chemical-specific DFR data would be needed to further refine exposure assessments or would 

add appreciably to our overall understanding of the availability of dislodgeable foliar pesticide 

residues for chlorsulfuron. 

Appendix H. 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 data are subject to ethics review 

pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics 

requirements. For certain studies that review may have included review by the Human Studies 

Review Board. Descriptions of data sources as well as guidance on their use can be found at: 

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.