UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: September 10, 2015 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Metsulfuron-methyl. Draft Human Health Risk Assessment in Support of 

Registration Review. 

PC Code: 122010 

Decision No.:505184 

Petition No.: NA 

Risk Assessment Type: Single Chemical 

Aggregate 

DP Barcode: D427414 

Registration No.: NA 

Regulatory Action: Registration Review 

Case No.: 7205 

TXR No.: NA CAS No.: 74223-64-6 

MRID No.: NA 40 CFR: § 180.428 

FROM: Monica Hawkins, Ph.D., M.P.H., Risk Assessor/Envi~o~ et Health Scientist~~ Evisabel Craig, Ph.D., DABT, Toxicologist · · I~ 

Julie Van Alstine, M.P.H., Environmental Health Sci n ·s ~~. \/"'-'""'>4-lvh. · 

Risk Assessment Branch VI ' '--

Health Effects Division (7509P) 

THROUGH: Donna S. Davis, Acting Branch Chief 

Risk Assessment Branch VI 

Health Effects Division (7509P) 

TO: Katherine St-Clair, Chemical Review Manager 

Tom Myers, Team Leader 

Kevin Costello, Branch Chief 

Risk Management and Implementation Branch 2 (RMIB 2) 

Pesticide Re-Evaluation Division (7508P) 

Since the last human health risk assessment and scoping document, the following updates have 

been incorporated for metsulfuron-methyl. 

I) The immunotoxicity and inhalation toxicity study requirements have been waived 

(TXR#0055652, 03113/2012 and TXR#0056723, 08/06/2013). 

2) Endpoints and points of departure have been selected for the incidental oral exposure 

scenario to assess spray drift exposure/risk estimates. 

3) The occupational and residential risk assessment has been updated to incorporate new 

science policies. 

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4) A coarse-screen estimated drinking water concentration (EDWC) was used to assess 

metsulfuron-methyl dietary exposure and risk. 

 

 
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Table of Contents 

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

2.0 HED Recommendations .................................................................................................... 5

2.1 Tolerance Considerations .................................................................................................. 5

2.2 Analytical Standards ......................................................................................................... 6

3.0 Introduction ........................................................................................................................ 6

3.1 Chemical Identity and Physical/Chemical Characteristics ............................................ 6

3.2 Pesticide Use Pattern and Anticipated Exposure Pathways .......................................... 6

3.3 Consideration of Environmental Justice ......................................................................... 9

4.0 Hazard Identification/Toxicology ..................................................................................... 9

4.1 Summary of Toxicological Effects .................................................................................. 10

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) ................................... 10

4.3 Toxicity Endpoint and Point of Departure Selections .................................................. 10

4.4 Endocrine Disruptor Screening Program ...................................................................... 12

5.0 Dietary Exposure and Risk Assessment ......................................................................... 13

5.1 Food Residue Profile ........................................................................................................ 13

5.2 Water Residue Profile...................................................................................................... 14

5.3 Dietary Exposure and Risk Estimates............................................................................ 15

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 16

6.1 Spray Drift ........................................................................................................................ 18

6.1.1   Combined Risk Estimates From Lawn Deposition Adjacent to Applications ............ 19

6.2 Residential Bystander Post-Application Inhalation Exposure .................................... 20

6.3 Residential Risk Estimates for Use in Aggregate Assessment ..................................... 20

7.0 Aggregate Exposure and Risk Assessment .................................................................... 21

8.0 Cumulative Exposure/Risk Characterization ............................................................... 22

9.0 Occupational Exposure/Risk Characterization ............................................................ 22

9.1 Occupational Handler Exposure/Risk Estimates .......................................................... 22

9.2 Occupational Post-Application Dermal Exposure/Risk Estimates ............................. 23

9.3 Occupational Post-Application Inhalation Exposure/Risk Estimates ........................ 24

10.0 Public Health and Pesticide Epidemiology Data ........................................................... 25

11.0 Literature References ...................................................................................................... 25

12.0 References ......................................................................................................................... 25

Appendix A. Toxicology Data Requirements and Toxicology Profile ................................... 26

Appendix B. Review of Human Research ................................................................................ 31

Appendix C. Occupational Short-term/Intermediate-term Handler Exposure and Risk 

Estimates for Metsulfuron-methyl. ........................................................................................... 32

Appendix D. Summary of Occupational and Residential Non-cancer Algorithms ............. 38

Appendix E. Dietary Exposure/Risk Modeling Input and Output ..................................... 49

Appendix F. Nomenclature and Physical/Chemical Properties ............................................. 51

Appendix G. Spray Drift Detailed Description ........................................................................ 53

Appendix H. Analytical Standards Summary ......................................................................... 55
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1.0 Executive Summary 

Metsulfuron-methyl is a sulfonylurea herbicide that is used to control broadleaf weeds on a 

variety of agricultural crops, on golf courses, turf, landscape plants, forestry, and ornamental 

trees. This document addresses exposures and risk estimates from the registered uses of 

metsulfuron-methyl required during Registration Review. The worst-case scenarios for the 

registered uses for metsulfuron-methyl are assessed in this document. 

The toxicology database for metsulfuron-methyl is complete and adequate for risk assessment. 

Subchronic inhalation, immunotoxicity, and neurotoxicity (acute and subchronic) studies are part 

of the current 40 CFR Part 158 Toxicology Data Requirements. However, the Hazard and 

Science Policy Council (HASPOC) determined that subchronic inhalation, immunotoxicity, and 

neurotoxicity (acute and subchronic) studies are not required at this time for metsulfuron-methyl 

(TXR#0055652, 03/13/2012 and TXR#0056723, 08/06/2013). The TOXLINE (National Library 

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

already considered. The latest risk assessment was conducted in 2002. No new toxicity and/or 

metabolism data have been received and the endpoints selected for the previous risk assessment 

remain the same.

The existing residue chemistry database for metsulfuron-methyl is complete and adequate for 

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

For dietary exposure, HED has conducted a screening-level chronic dietary exposure and risk 

assessment for metsulfuron-methyl using tolerance-level residues in foods and a sulfonylureaclass-wide screening-level estimate of residues in drinking water. Chronic dietary exposure and 

risk estimates (food and drinking water) 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. Metsulfuron-methyl is 

classified as “not likely to be carcinogenic to humans”; therefore, a cancer dietary assessment 

was not conducted for metsulfuron-methyl. 

The residential handler exposure and risk estimates indicate that the dermal MOEs range from 

25,000 to 990,000,000 and the inhalation MOEs range from 1,200,000 to 2,300,000,000 and are 

greater than HED’s LOC (i.e., MOEs are ≥ 100). Metsulfuron-methyl is applied to lawns, parks, 

and golf courses; therefore, residential post-application exposure was assessed. Dermal postapplication risks were assessed for adults, children 11 to 16 years old, and children 1 < 2 years 

old. All adult and older children golfing dermal risk estimates for both liquid and granular 

formulations are greater than HED’s level of concern (MOEs ≥ 100). All adults and children 1 < 

2 years old on treated turf dermal risk estimates for both liquid and granular formulations MOEs 

range from 4,200 to 2,000,000. All children 1 < 2 years old oral non-dietary ingestion risk from 

hand-to-mouth activity on treated turf estimates for both liquid and granular formulations MOEs 

range from 56,000 to 25,000,000. A quantitative spray drift assessment was conducted. 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 utilize the Volatilization 

Screening Analysis (i.e., flux studies, route-specific inhalation toxicological studies) to 

determine if data or further analysis is required for metsulfuron-methyl. 
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An aggregate assessment has been conducted for metsulfuron-methyl, and aggregate exposure 

and risk estimates do not exceed HED’s level of concern (LOC). 

 

The occupational handler exposure and risk estimates based on the highest application rate and 

amount handled scenario indicate that the short- and intermediate-term dermal MOEs and 

inhalation MOEs are not of concern to HED (i.e., MOEs ≥ 100) at baseline attire (i.e., no gloves 

and no respirator). The occupational handler dermal MOEs range from 180 to 9,700,000 and the 

inhalation MOEs range from 1,300 to 2,600,000,000. Occupational post-application exposure 

and risk estimates indicate that the short- and intermediate-term margins of exposure are not of 

concern to HED on the day of application (i.e., MOE > the LOC of 100). The MOEs range from 

410 to 51,000. Based on the Agency's current practices, a quantitative non-cancer occupational 

post-application inhalation exposure assessment was not performed for metsulfuron-methyl at 

this time. If new policies or procedures are put into place, the Agency may revisit the need for a 

quantitative occupational post-application inhalation exposure assessment for metsulfuronmethyl. 

The restricted entry interval (REI) of 4, 12, or 48 hours specified on the registered labels is based 

on the acute toxicity of metsulfuron-methyl. Upon review of the criteria for the active ingredient 

only, it appears that metsulfuron-methyl 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 metsulfuron-methyl. 

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

intentionally exposed to a pesticide or other chemical. For a list of data sources see appendix B. 

2.0 HED Recommendations 

2.1 Tolerance Considerations 

The existing tolerances for residues of metsulfuron-methyl (40 CFR §180.428) are supported by 

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

for residues of metsulfuron-methyl. Canada has established MRLs for metsulfuron-methyl 

which are harmonized with U.S. tolerances. 

HED notes that the tolerance expressions for metsulfuron-methyl in 40 CFR §180.452 require 

revisions to state the following: 

40 CFR §180.428(a)(1): 

Tolerances are established for the residues of the herbicide metsulfuron-methyl, 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 the sum 

of metsulfuron-methyl (methyl 2-[[[[(4-methoxy-6-methyl-1,3,5-triazin-2-

yl)amino]carbonyl]amino]sulfonyl]benzoate) and free and conjugated methyl 2-[[[[(4-

methoxy-6-methyl-1-,3,5-triazin-2-yl)amino]carbonyl]amino]sulfonyl]-4-
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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hydroxybenzoate, calculated as the stoichiometric equivalent of metsulfuron-methyl, in 

or on the commodity. 

40 CFR §180.428(a)(2): 

Tolerances are established for the residues of the herbicide metsulfuron-methyl, including 

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

with the tolerance levels is to be determined by measuring only metsulfuron-methyl 

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

yl)amino]carbonyl]amino]sulfonyl]benzoate), in or on the commodity. 

2.2 Analytical Standards 

An analytical standard is required for the 4-hydroxy metsulfuron methyl metabolite (A1), as 

outlined in Appendix H. 

3.0 Introduction 

3.1 Chemical Identity and Physical/Chemical Characteristics 

The chemical structure and nomenclature of metsulfuron-methyl and a detailed description of the 

physicochemical properties of metsulfuron-methyl are provided in Appendix F.

3.2 Pesticide Use Pattern and Anticipated Exposure Pathways 

Metsulfuron-methyl is currently used on a variety of agricultural crops, on golf courses, turf, 

landscape plants, forestry, and ornamental trees. There are several end-use product labels 

registered with metsulfuron-methyl as the active ingredient. These include water-dispersible 

granules (WDG)/dry flowable (DF) and granular formulations. Most of the registered products 

are applied via aerial, chemigation, groundboom, or with handheld equipment. The single 

application rate of the registered uses for metsulfuron-methyl range from 0.0019 to 0.2 lb ai/A. 

Exposure Pathways 

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

registered uses of metsulfuron-methyl, so exposure in residential or occupational settings can 

occur. There is the potential for indirect exposure (incidental oral and dermal) to metsulfuronmethyl related to spray drift. Homeowners and agricultural workers may be exposed (dermal 

and inhalation) to metsulfuron-methyl during mixing, loading, and/or applying the herbicide as 

well as during post-application activities. 

Based on the use pattern for metsulfuron, short- and intermediate-term dermal and inhalation 

exposures are anticipated for occupational handlers and post-application workers and short-term 

dermal and inhalation exposures for residential handlers and residential post-application 
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individuals. The metsulfuron-methyl labels require handlers to wear baseline attire (i.e., a long 

sleeved shirt, long pants, shoes plus socks) and chemical-resistant gloves. 

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

metsulfuron-methyl. 

Table 3.2. Summary of Registered Uses of Metsulfuron-methyl.

Application 

Equipment 

Formulation 

Maximum 

Application 

Rate 

REI Use Directions and 

Limitations 

Barley

Groundboom, 

Aerial WDG/DF 0.0078 lb ai/A 4 hours

Do not apply this product 

through any type of 

irrigation system.

Bermuda Grass

Groundboom, 

Aerial WDG/DF 0.023 lb ai/A 12 hours

Do not apply this product 

through any type of 

irrigation system.

Black Spruce

Groundboom, 

Aerial, 

Hand-Held

WDG/DF 0.05 lb ai/A 4 hours

Following an application of 

this product, do not use 

sprayer for application to 

agricultural or ornamental 

crops. The mixing and 

application equipment must 

be used for forestry and 

noncrop applications only.

Christmas Trees

Groundboom, 

Aerial, 

Hand-Held 

WDG/DF 

0.2 lb ai/A 

(0.002 lb ai/gallon) 4 hours 

Following an application of 

this product, do not use 

sprayer for application to 

agricultural or ornamental 

crops. The mixing and 

application equipment must 

be used for forestry and 

noncrop applications only.

Commercial Lawns 

Groundboom, 

Aerial DF 0.09 lb ai/A Not Specified Do not apply through any 

type of irrigation system. 

Conifer 

Groundboom, 

Aerial, 

Hand-Held 

WDG/DF 0.2 lb ai/A 4 hours 

Following an application of 

this product, do not use 

sprayer for application to 

agricultural or ornamental 

crops. The mixing and 

application equipment must 

be used for forestry and 

noncrop applications only.

Forestry
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Table 3.2. Summary of Registered Uses of Metsulfuron-methyl.

Application 

Equipment 

Formulation 

Maximum 

Application 

Rate 

REI Use Directions and 

Limitations 

Groundboom, 

Aerial, 

Hand-Held 

WDG/DF 0.2 lb ai/A 

(0.002 lb ai/gallon)

4 hours 

Following an application of 

this product, do not use 

sprayer for application to 

agricultural or ornamental 

crops. The mixing and 

application equipment must 

be used for forestry and 

noncrop applications only.

Golf Courses 

Groundboom, 

Handwand, 

Hose-end, 

Backpack 

WDG/DF 

0.04 lb ai/A 

(0.0004 lb 

ai/gallon; 

0.00000092 lb 

ai/ft2

) 

4 hours Do not apply to turf less 

than one year old. 

Landscape Turf, Lawns, Parks, Cemeteries 

Groundboom WDG/DF 

0.04 lb ai/A 

(0.0004 lb 

ai/gallon; 

0.00000092 lb 

ai/ft2

) 

4 hours Do not apply to turf less 

than one year old. 

Rights-of-Way 

Groundboom, 

Aerial WDG/DF

0.15 lb ai/A 

(0.0015 lb 

ai/gallon) 

4 hours Do not use this product in 

California.

Sugarcane

Groundboom, 

Aerial WDG/DF 0.125 lb ai/A 4 hours

Do not apply this product 

to irrigated land where 

tailwater will be used to 

irrigate crops other than 

sugarcane.

Pastures, Rangeland

Groundboom, 

Aerial WDG/DF 0.059 lb ai/A 4 hours

Do not apply this product 

through any type of 

irrigation system.

Residential Lawns

Drop, RotaryType Spreader, 

Shaker Can 

G 

0.04 lb ai/A 

(0.00000092 lb 

ai/ft2

)

NS

Do not apply on or under 

branch spread area of trees, 

shrubs, bedding plants, 

flowers, or garden plants. 

Sod 

Groundboom WDG/DF 0.04 lb ai/A 4 hours Do not apply to turf less 

than one year old.

Sorghum 

Groundboom, WDG/DF 0.0019 lb ai/A 4 hours Do not exceed one 

application per year.
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Table 3.2. Summary of Registered Uses of Metsulfuron-methyl.

Application 

Equipment 

Formulation 

Maximum 

Application 

Rate 

REI Use Directions and 

Limitations 

Aerial

Tree Injection 

Injection WDG/DF 0.0047 lb ai/day 48 hours 

Apply 1 milliliter of 

solution at each injection 

site around the tree with no 

more than one inch 

intervals between cut 

edges. 

Triticale

Groundboom, 

Aerial WDG/DF 0.00375 lb ai/A 4 hours Do not use on grasses 

grown for seed. 

Wheat 

Groundboom, 

Aerial WDG/DF 0.0078 lb ai/A 4 hours

Do not apply this product 

through any type of 

irrigation system.

WDG = water-dispersible granule; DF = dry flowable; G = Granular 

3.3 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 (USDA) under the National Health and Nutrition Examination Survey, What We Eat 

in America, (NHANES/WWEIA; 2003-2008) and are used in pesticide risk assessments for all 

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

on age 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 
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The toxicology database for metsulfuron-methyl is complete and adequate for risk assessment. 

Subchronic inhalation, immunotoxicity, and neurotoxicity (acute and subchronic) studies are part 

of the current 40 CFR Part 158 Toxicology Data Requirements. However, the Hazard and 

Science Policy Council (HASPOC) determined that subchronic inhalation, immunotoxicity, and 

neurotoxicity (acute and subchronic) studies are not required at this time for metsulfuron-methyl 

(TXR#0055652, 03/13/2012 and TXR#0056723, 08/06/2013). The TOXLINE (National Library 

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

already considered. The latest risk assessment was conducted in 2002 (W. Cutchin, D281907, 

6/26/2002). No new toxicity and/or metabolism data have been received and the endpoints 

selected for the previous risk assessment remain the same. For a summary of the acute, 

subchronic and chronic toxicity profile, see Appendix A. 

4.1 Summary of Toxicological Effects 

Metsulfuron-methyl has low acute toxicity by oral, dermal, and inhalation routes of exposure. It 

is a severe eye irritant (Category I) but does not cause primary dermal irritation. Metsulfuronmethyl is not a skin sensitizer. In mammals, metsulfuron methyl exhibited generalized, 

nonspecific toxicity (decreased body weight) and did not appear to have specific target organ 

toxicity. Rats appear to be the most sensitive species tested. There is no evidence that 

metsulfuron-methyl is a developmental, reproductive, neurotoxic, carcinogenic, mutagenic or 

immunotoxic chemical. The HED Hazard Identification Assessment Review Committee 

(HIARC), in accordance with the 1999 Draft Guidance for Carcinogenic Risk Assessment, 

classified metsulfuron methyl as “not likely to be carcinogenic to humans.” 

Metsulfuron-methyl is well absorbed regardless of dose or treatment regimen (single gavage 

dose alone or after repeated dietary feeding). The primary route of excretion is via the urine (71-

95%) followed by fecal elimination (4.8-13.3%) and levels remaining in the tissues are 

negligible. 

4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

The toxicity database of metsulfuron-methyl is complete and adequate to assess the qualitative or 

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

quantitative susceptibility in the young; there is no evidence of neurotoxicity with metsulfuron 

methyl; and exposure estimates are unlikely to underestimate risk; therefore, the10-fold FQPA 

Safety Factor is reduced to 1X.

4.3 Toxicity Endpoint and Point of Departure Selections 

There have been no changes to the prior dose-response assessment and cancer classification. 

It is recognized that the studies in the toxicological database for metsulfuron-methyl, including 

those used for endpoint selection, have not been updated to reflect current policy and may be 

considered conservative. However, the current PODs are protective of the effects observed in 
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the metsulfuron-methyl database and any updates would not impact the overall findings of the 

risk assessment given the current risk picture for metsulfuron-methyl. 

Table 4.3.1. Metsulfuron-methyl Summary of Toxicological Doses and Endpoints for Use in 

Dietary Human Health Risk Assessments. 

Exposure 

Scenario 

Point of 

Departure 

Uncertainty/ 

FQPA SFs 

Population Adjusted 

Dose for Risk 

Assessment 

Study and Toxicological Effects

Acute Dietary 

(General 

Population 

including 

Infants and 

Children) 

A single dose effect relevant to the general US population including infants and children was not 

identified in the toxicity studies conducted with metsulfuron-methyl. 

Acute dietary 

(Females 13-49 

years of age) 

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

rabbits. 

Chronic Dietary 

(All 

Populations) 

NOAEL = 25 

mg/kg/day 

UFA = 10x 

UFH =10x 

FQPA SF= 1x 

RfD= 0.25 mg/kg/day 

cPAD = 0.25 

mg/kg/day 

Rat, Oral Chronic/Carcinogenicity 

Toxicity Study 

MRID 144477 (1985) 

LOAEL = 250 mg/kg/day based on 

decreased body weight 

Incidental oral 

(short- & 

intermediateterm) 

NOAEL = 34 

mg/kg/day 

UFA = 10x 

UFH =10x 

FQPA SF= 1x 

Residential LOC for 

MOE = 100 

Rat, 2 Generation Reproduction 

Study 

MRID 151028 (1985) 

LOAEL = 342 mg/kg/day based on 

decreased premating (FO) body 

weights. 

Dermal 

exposure (all 

durations) 

Dermal 

NOAEL = 125 

mg/kg/day 

UFA = 10x 

UFH =10x 

FQPA SF= 1x 

Residential LOC for 

MOE = 100 

Rabbit, 21 Day Dermal Exposure 

Study 

MRID 40357803 (1987), 

41247801 (1989) 

LOAEL = 500 mg/kg/day based on 

increased incidence of diarrhea. 

Inhalation 

exposure 

(short- & 

intermediate 

term) 

Oral 

NOAEL = 34 

mg/kg/day 

UFA = 10x 

UFH =10x 

FQPA SF= 1x 

IA = 100% 

Residential LOC for 

MOE = 100 

Rat, 2 Generation Reproduction 

Study 

MRID 151028 (1985) 

LOAEL = 342 mg/kg/day based on 

decreased premating (FO) body 

weights. 

Inhalation 

exposure (long 

term) 

Oral 

NOAEL = 25 

mg/kg/day 

UFA = 10x 

UFH =10x 

FQPA SF= 1x 

IA = 100% 

Residential LOC for 

MOE = 100 

Rat, Oral Chronic/Carcinogenicity 

Toxicity Study 

MRID 144477 (1985) 

LOAEL = 250 mg/kg/day based on 

decreased body weight 

Cancer (oral, 

dermal, 

inhalation) 

Metsulfuron methyl is classified as “not likely to be carcinogenic to humans.” This is based on the 

lack of evidence of carcinogenicity in mice and rats, no evidence of mutagenicity in acceptable 

studies, and the non-carcinogenic potential of structurally related compounds. 

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 = 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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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). IA = 

inhalation absorption factor. 

Table 4.3.2. Metsulfuron-methyl Summary of Toxicological Doses and Endpoints for 

Metsulfuron methyl 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 

(all durations) 

Dermal 

NOAEL = 125 

mg/kg/day 

UFA = 10x 

UFH =10x 

Occupational LOC for 

MOE = 100 

Rabbit, 21 Day Dermal 

Exposure Study 

MRID 40357803 (1987), 

41247801 (1989) 

LOAEL = 500 mg/kg/day 

based on increased incidences 

of diarrhea. 

Inhalation exposure 

(Short- & 

intermediate term) 

Oral 

NOAEL = 34 

mg/kg/day 

UFA = 10x 

UFH =10x 

IA = 100% 

Occupational LOC for 

MOE = 100 

Rat, 2 Generation 

Reproduction Study 

MRID 151028 (1985) 

LOAEL = 342 mg/kg/day 

based on decreased premating 

(FO) body weights. 

Inhalation exposure 

(long term) 

Oral 

NOAEL = 25 

mg/kg/day 

UFA = 10x 

UFH =10x 

IA = 100% 

Occupational LOC for 

MOE = 100 

Rat, Oral 

Chronic/Carcinogenicity 

Toxicity Study 

MRID 144477 (1985) 

LOAEL = 250 mg/kg/day 

based on decreased body 

weight 

Cancer (oral, 

dermal, inhalation) 

Metsulfuron methyl is classified as “not likely to be carcinogenic to humans.” This is 

based on the lack of evidence of carcinogenicity in mice and rats, no evidence of 

mutagenicity in acceptable studies, and the non-carcinogenic potential of structurally 

related compounds. 

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. IA = inhalation absorption factor.

4.4 Endocrine Disruptor Screening Program 

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

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

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

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

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

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

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

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

taxonomic groups. As part of its most recent registration decision for metsulfuron-methyl, EPA 

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

metsulfuron-methyl 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, 20131

 and includes some 

pesticides scheduled for Registration Review and chemicals found in water. 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 Food Residue Profile 

The existing residue chemistry database for metsulfuron-methyl is adequate for risk assessment 

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

residues in plants and animals is adequately understood. Adequate analytical methods (highperformance liquid chromatography/ultraviolet detection [HPLC/UV]) exist for data collection 

and tolerance enforcement. The HED Metabolism Assessment Review Committee (MARC) 

determined that the residues of concern for risk assessment and tolerance enforcement for plants 

are metsulfuron-methyl and its metabolites, methyl 2-[[[[(4-methoxy-6-methyl-1,3,5-triazin-2-

yl)amino]carbonyl]amino]sulfonyl]-4-(beta-D-glycopyranosyl)benzoate (Metabolite A) and 

methyl 2-[[[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino]carbonyl]amino]sulfonyl]-4-

hydroxybenzoate (Metabolite A1) (Memo, B. Cutchin, 12/17/01; D279786). Metabolite A1 is 

formed from Metabolite A through enzymatic hydrolysis. The residue of concern for risk 

assessment and tolerance enforcement for livestock is metsulfuron-methyl only. 

 

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/
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Metsulfuron-methyl is the principal degradate in water of the active ingredient iodosulfuronmethyl-sodium (PC Code 122021). As a result, metsulfuron-methyl is a residue of concern in 

drinking water following application of iodosulfuron-methyl-sodium. Metsulfuron-methyl is not 

a residue of concern for risk assessment and tolerance enforcement in plants and livestock 

following iodosulfuron-methyl-sodium applications; therefore, the dietary exposure and risk 

assessment incorporates tolerance-level residues resulting from the application of metsulfuronmethyl only and a screening-level drinking water estimate. HED is confident that the dietary 

assessment will not underestimate the dietary risks of the general U.S. population or any 

population subgroup due to food and drinking exposures to metsulfuron-methyl. 

5.2 Water Residue Profile 

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. Rather than produce chemical-specific estimated EDWCs 

following the usual assessment procedures, EFED provided coarse-screen estimates that should 

exceed upper-bound chemical-specific EDWCs for any SU. This was achieved by using model 

inputs that represent the use pattern of highest exposure from any SU, the highest soil mobility of 

any SU residue of concern, and persistence to any route of degradation over time. The resulting 

highest coarse-screen EDWCs from PRZM-GW can be used as a conservative estimate of 

exposure and are summarized in Table 5.2.1 (G. Orrick, D427429, 8/12/15). 

The chronic dietary assessment for metsulfuron-methyl used the coarse-screen post-breakthrough 

mean value of 492 μg/L (0.492 ppm). HED notes that metsulfuron-methyl is the principal 

degradate of iodosulfuron-methyl-sodium in water. HED is confident that the use of screeninglevel EDWCs in the chronic dietary assessment does not underestimate the dietary risks of the 

general U.S. population or any population subgroup due to food and drinking exposures to 

metsulfuron-methyl. 

Table 5.2.1. PRZM-GW Coarse-Screen EDWCs for Sulfonylureas1. 

Modeled Scenario Kd or KOC

Initial Application 

Dates (days postemergence) 

Max. Daily Conc. 

(μg/L) 

Mean 

Breakthrough 

Time (yrs) 

Postbreakthrough 

Mean (μg/L) 

WI corn 

Kd 7 449 11.5 415 

KOC 7 504 6.9 425 

DMV corn 

Kd 7 489 5.3 369 

KOC 7 560 3.3 378 

FL citrus 

Kd 7 429 3.2 351 

KOC 7 467 2.3 349 

FL potato 

Kd 7 375 2.6 272 

KOC 7 407 2.2 275 

GA peanut 

Kd 7 197 5.2 156 

KOC 7 206 3.9 158 

NC cotton 

Kd 7 640 8.7 492 

Kd 37 641 8.7 491 
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Table 5.2.1. PRZM-GW Coarse-Screen EDWCs for Sulfonylureas1. 

Modeled Scenario Kd or KOC

Initial Application 

Dates (days postemergence) 

Max. Daily Conc. 

(μg/L) 

Mean 

Breakthrough 

Time (yrs) 

Postbreakthrough 

Mean (μg/L) 

Kd 67 637 8.7 490 

KOC 7 742 5.7 484

KOC 37 751 5.7 483 

KOC 67 744 5.7 482 1

 Maximum values are bolded. 

5.3 Dietary Exposure and Risk Estimates 

HED has conducted a screening-level chronic dietary risk assessment for metsulfuron-methyl 

using tolerance-level residues in foods and the sulfonylurea-class-wide screening-level estimate 

of residues in drinking water (G. Orrick, D427429, 8/12/15). Exposure and risk estimates were 

obtained from the Dietary Exposure Evaluation Model using the Food Commodity Intake 

Database (DEEM-FCID; version 3.16). The model uses food consumption data from the 2003-

2008 National Health and Nutrition Examination Survey/What We Eat in America 

(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 

chronic population adjusted dose (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 utilized 4.4% of the cPAD for the general U.S. 

population and 11% of the cPAD for all infants (<1 year 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 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 E. HED did not 

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

acute dietary assessment. Metsulfuron-methyl is classified as “not likely to be carcinogenic to 

humans”; therefore, a cancer dietary assessment was not conducted for metsulfuron-methyl. 

Table 5.3. Summary of Chronic Dietary Exposure (Food and Drinking Water) and Risk for Metsulfuronmethyl1

.

Population Subgroup 

Chronic Dietary 

Dietary Exposure 

(mg/kg/day) % cPAD 

General U.S. Population 0.010929 4.4 

All Infants (<1 year old) 0.027296 11 

Children 1-2 years old 0.017643 7.1 

Children 3-5 years old 0.014355 5.7 

Children 6-12 years old 0.010151 4.1 

Youth 13-19 years old 0.008090 3.2 

Adults 20-49 years old 0.010718 4.3 

Adults 50-99 years old 0.010538 4.2 

Females 13-49 years old 0.010655 4.3 
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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/Risk Characterization 

There are existing residential uses that have been assessed in this document to reflect updates to 

HED’s 2012 Residential SOPs along with policy changes for body weight assumptions. 

Therefore, a quantitative assessment of residential handlers and post-application risks for 

metsulfuron-methyl was conducted in line with the revised 2012 Residential SOPs. The 

exposure and risk estimates are provided in Table 6.0.1., 6.0.2., and 6.0.3. All estimated risks 

are above HED’s LOC for residential risk (MOE > 100) and are not of concern. 

Note: HED anticipates that residential handler exposure from mixing/loading liquids for tree 

injection use is less than would be anticipated from occupational handler exposure for tree 

injection. It is not anticipated that as many trees would be treated per day in a residential setting 

as in an occupational setting. Therefore, the occupational handler assessment that was conducted 

is considered protective of the residential handler exposures and, accordingly, a quantitative 

residential handler assessment for this scenario was not conducted. 

Table 6.0.1. Residential Handler Non-cancer Exposure and Risk Estimates for Metsulfuron-methyl. 

Exposure 

Scenario 

Dermal 

Unit 

Exposure 

(mg/lb ai) 

Inhalation 

Unit 

Exposure 

(mg/lb ai) 

Maximum 

Application Rate1

Area 

Treated or 

Amount 

Handled 

Daily2

Dermal 

(LOC = 100) 

Inhalation 

(LOC = 100) 

Dose 

(mg/kg/day)3 MOE4 Dose (mg/kg/day)5 MOE6

Loader/Applicator for Granules 

Push-type 

spreaders 0.81 0.0026 0.04 lb ai/A 0.5 A 0.0002 620,000 0.00000065 52,000,000 

Belly 

grinders 360 0.039 

0.00000092 lb ai/ft2

1200 ft2 0.005 25,000 0.00000054 63,000,000 

Spoon 6.2 0.087 

100 ft2

0.0000071 18,000,000 0.0000001 340,000,000 

Cup 0.11 0.013 0.00000013 990,000,000 0.000000015 2,300,000,000 

Hand 

dispersal 160 0.38 0.00018 680,000 0.00000044 78,000,000 

Shaker can 0.11 0.013 0.00000013 990,000,000 0.000000015 2,300,000,000 

Mixer/Loader/Applicator for Liquids 

Manuallypressurized 

handwand 

63 0.018 0.0004 lb ai/gallon 5 gallons 0.0016 79,000 0.00000045 76,000,000 

Hose-end 

sprayer 

13.4 0.022 0.04 lb ai/A 0.5 A 0.0034 37,000 0.0000055 6,200,000 

Backpack 130 0.14 0.0004 lb ai/gallon 5 gallons 0.0033 38,000 0.0000035 9,700,000 

Sprinkler 

can 13.4 0.022 0.00000092 lb ai/ft2 1000 ft2 0.00015 810,000 0.00000025 130,000,000 

Mixer/Loader/Applicator for Dry Flowables 

Manuallypressurized 

handwand 

69 1.1 0.0004 lb ai/gallon 5 gallons 0.0017 72,000 0.000028 1,200,000 

Hose-end 

sprayer 

13.4 0.022 0.04 lb ai/A 0.5 A 0.0034 37,000 0.0000055 6,200,000 

Backpack 69 1.1 0.0004 lb ai/gallon 5 gallons 0.0017 72,000 0.000028 1,200,000 

Sprinkler 

can 13.4 0.022 0.00000092 lb ai/ft2 1000 ft2

 0.00015 810,000 0.00000025 130,000,000 

1. Based on registered labels (see table 3.2). 

2. Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html). 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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3. Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or 

gallons/day) ÷ Body Weight (80 kg). 

4. Dermal MOE = Dermal NOAEL (125 mg/kg/day) ÷ Dermal Dose (mg/kg/day). 

5. Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or 

gallons/day) ÷ Body Weight (80 kg). 

6. Inhalation MOE = Inhalation NOAEL (34 mg/kg/day) ÷ Inhalation Dose (mg/kg/day). 

7. Total MOE = NOAEL (mg/kg/day) ÷ (Dermal Dose + Inhalation Dose) 

For post-application scenarios, all adult and children golfing dermal risk estimates for both liquid 

and granular formulations are greater than the LOC (MOEs ≥ 100). In addition, all adults and 

children on treated turf dermal risk estimates for both liquid and granular formulations are 

greater than the LOC (MOEs ≥ 100). Therefore, no risks of concern were identified for either of 

these scenarios. A summary of the adult and children short-term dermal exposure and risk 

estimates is shown in Table 6.0.2. 

Table 6.0.2. Summary of Residential Post-application Non-cancer Exposure and Risk Estimates for Metsulfuron-methyl.

Lifestage Post-application Exposure Scenario Application Rate 

(lb ai/A)1

TTR 

(ug/cm2)

Dermal Dose 

2(mg/kg/day)2 Dermal MOEs3

Liquid Formulations

Adult 

Dermal 

Physical Activities on Turf

0.04 0.004 

0.015 8,300 

Mowing 0.00031 410,000 

Golfing 0.0012 110,000 

Child 11 < 16 years old Mowing 0.00035 360,000 

Child 11 < 16 years old Golfing 0.0014 91,000 

Child 6 < 11 years old Dermal Golfing 0.0016 78,000 

Child 1 < 2 years old Dermal Physical Activities on Turf 0.03 4,200 

Granular Formulations

Adult Dermal 

Physical Activities on Turf

0.04 0.001 

0.003 37,000 

Mowing 0.0000611 2,000,000 

Golfing 0.00024 530,000 

Child 11 < 16 years old Dermal Mowing 0.0000702 1,800,000 

Child 11 < 16 years old Dermal Golfing 0.00027 460,000 

Child 6 < 11 years old Dermal Golfing 0.00032 390,000 
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Table 6.0.2. Summary of Residential Post-application Non-cancer Exposure and Risk Estimates for Metsulfuron-methyl.

Lifestage Post-application Exposure Scenario Application Rate 

(lb ai/A)1

TTR 

(ug/cm2)

Dermal Dose 

2(mg/kg/day)2 Dermal MOEs3

Child 1 < 2 years old Dermal Physical Activites on Turf 0.01 19,000 

1. Application rates = maximum application rates from labels. 

2. Dose (mg/kg/day) equations provided in Appendix A. 

3. Dermal MOE = NOAEL (125 mg/kg/day) / Dermal Dose (mg/kg/day)

All children oral non-dietary ingestion risk estimates for both liquid and granular formulations 

are greater than HED’s LOC (MOEs ≥ 100) and therefore, are not of concern. A summary of the 

children short-term oral non-dietary ingestion exposure and risk estimates is shown in Table 

6.0.3. HED did not identify an appropriate endpoint for acute dietary assessment. Therefore, an 

episodic granular ingestion exposure and risk estimate was not calculated for children 1 < 2 years 

old.

Table 6.0.3. Short-Term Oral Non-dietary Ingestion Residential Post-application Exposure and Risk Estimates for 

Metsulfuron-methyl 

Lifestage Post-application Exposure Scenario Application Rate 1

(lb ai/A) 

TTR 

(ug/cm2) 

Oral Dose 2

(mg/kg/day) 

Oral 

MOEs 3

Liquids

Child 1 < 2 year old Oral 

Hand-to-Mouth 

0.04 

0.00007 0.0006 56,000 

Object-to-Mouth 0.004 0.00002 1,800,000

Soil Ingestion 0.298 0.00000146 25,000,000

Granulars

Child 1 < 2 year old Oral 

Hand-to-Mouth 

0.04

0.00001 0.0001 560,000 

Object-to-Mouth 0.001 0.0000037 9,200,000

Soil Ingestion 0.298 0.00000146 25,000,000

1. Application rates = maximum application rates from labels. 

2. Dose (mg/kg/day) equations provided in Appendix A.

3. Oral MOE = NOAEL (34 mg/kg/day) / Oral Dose (mg/kg/day). 

Turf Transferable Residue (TTR): In accordance with 40CFR158, TTR data are required for all 

occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses 

that could result in post-application exposure to turf. HED developed a waiver policy for TTR 

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

10 times higher than the level of concern (LOC), the TTR studies can be waived. 

Since the estimated residential turf post-application exposure for residential turf/mower/golf 

course using default TTR values for metsulfuron-methyl is minimal in comparison to the level of 

concern (i.e., the calculated MOE is greater than 10 times higher than the level of concern, MOE 

= 78,000 compared to the LOC of 100); EPA is waiving the 40 CFR TTR data requirement. In 

this instance, it is unlikely that chemical-specific TTR data would be needed to further refine 

exposure assessments or would add appreciably to our general understanding of the availability 

of turf transferable pesticide residues. 

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 G. 
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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. Metsulfuron-methyl is used on a 

variety of agricultural crops and can be applied via groundboom and aerial equipment. The 

spray drift assessment was conducted using the highest registered application rate of 0.2 lb 

ai/acre for use on forestry3. The recommended drift scenario screening level options are listed 

below: 

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

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 to 

medium spray type and a series of other parameters, which will be described in more 

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

application/drift event).4

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 metsulfuron-methyl related to spray drift result 

in no risks of concern at the field edge for either groundboom or for aerial applications. Results 

are presented in Tables 6.1.1. and 6.1.2. below.

Table 6.1.1. Adult Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for Metsulfuronmethyl for the Dermal Route of Exposure

Crop/Rate 

Group 

Spray Type/ 

Nozzle 

Configuration 

Application 

Rate (lb ai/A) 

Estimated or Adjusted 

TTR (ug/cm2) 

At Edge 

Dermal MOE 

Forestry1

Aerial Fine to Medium 

0.2 0.02223 

6,500 

Groundboom High Boom Very 

fine to Fine 8,900 

1

 There is some uncertainty associated with the drift predictions associated with forestry uses because in some situations pesticides like 

metsulfuron-methyl are applied in rugged terrain using rotary aircraft and smaller droplets. A more appropriate modeling approach is currently 

under development for such situations. Even so, this would not alter the risk conclusions for the current human health risk assessment spray drift 

scenario because, in the case of metsulfuron-methyl, if the 100% of application rate assumption is used rather than the screening level 

assumptions, there would be no risks of concern. 

 

3

There is some uncertainty associated with the drift predictions associated with forestry uses because in some 

situations pesticides like metsulfuron-methyl are applied in rugged terrain using rotary aircraft and smaller droplets. 

A more appropriate modeling approach is currently under development for such situations. Even so, this would not 

alter the risk conclusions for the current human health risk assessment spray drift scenario because, in the case of 

metsulfuron-methyl, if the 100% of application rate assumption is used rather than the screening level assumptions, 

there would be no risks of concern. 

4

 AgDrift® allows for consideration of even finer spray patterns characterized as very fine to fine. However, this 

spray pattern was not selected as the common screening basis since it is used less commonly for most agriculture. If 

assessors identify this use pattern, then it should be used as the screening criteria and deposition values associated 

with it should be provided. Justification for including this spray quality should be included in any assessment based 

on specific label directions for its use. 
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Table 6.1.2. Children (1 < 2 years old) Risk Estimates (MOEs) Related to Indirect Exposure to Spray 

Drift for Metsulfuron-methyl for Dermal and Incidental Oral Route of Exposure 

Crop/Rate 

Group 

Spray Type/ Nozzle 

Configuration 

Application 

Rate (lb ai/A) 

Estimated 

or 

Adjusted 

TTRt

(ug/cm2) 

 At Edge At 

Edge 

 Dermal 

MOE Incidental Oral 

MOE 

Forestry1

Aerial Fine to Medium 

0.2 0.02223

 

3,300 43,000 

Groundboom High Boom Very 

fine to Fine 

 

4,500 60,000 1

 There is some uncertainty associated with the drift predictions associated with forestry uses because in some situations pesticides like 

metsulfuron-methyl are applied in rugged terrain using rotary aircraft and smaller droplets. A more appropriate modeling approach is currently 

under development for such situations. Even so, this would not alter the risk conclusions for the current human health risk assessment spray drift 

scenario because, in the case of metsulfuron-methyl, if the 100% of application rate assumption is used rather than the screening level 

assumptions, there would be no risks of concern.

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 (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 utilize this analysis to determine if data (i.e., flux 

studies, route-specific inhalation toxicological studies) or further analysis is required for 

metsulfuron-methyl. 

6.3 Residential Risk Estimates for Use in Aggregate Assessment 

Table 6.3.1 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for metsulfuron-methyl. 

 The recommended residential exposure for use in the adult short-term aggregate 

assessment reflects inhalation exposure from turf applications from manually-pressurized 

handwand. 

 The recommended residential exposure for use in the children 1 to <2 years old shortterm aggregate assessment reflects hand-to-mouth exposures from post-application 

exposure to turf applications of liquid formulations. 
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Table 6.3.1. Recommendation for the Residential Exposures for the Metsulfuron-methyl Aggregate Assessment

Lifestage Exposure 

Scenario 

Dose (mg/kg/day)1 MOE2

Inhalation Oral Total Inhalation Oral Total 

Adults 

Turf 

Applications 

From 

ManuallyPressurized 

Handwand 

Equipment 

(Dry 

Flowables) 

0.000028 N/A 0.000028 1,200,000 N/A 1,200,000

Child 1 to <2 

yrs old 

Hand-toMouth 

(Liquids) 

N/A 0.0006 0.0006 N/A 56,000 56,000 

1 Dose = the highest dose for each applicable lifestage of all residential scenarios assessed. Total = dermal + inhalation + incidental oral (where 

applicable). 

2 MOE = the MOEs associated with the highest residential doses. Total = 1 ÷ (1/Dermal MOE) + (1/Inhalation MOE) + (1/Incidental Oral 

MOE), where applicable. 

7.0 Aggregate Exposure and Risk Assessment 

HED did not conduct an acute aggregate dietary exposure/risk assessment due to the lack of an 

endpoint appropriate for acute dietary assessment. A cancer aggregate risk assessment was not 

performed because metsulfuron-methyl is classified by HED as “not likely to be carcinogenic to 

humans.” 

There is potential short- and intermediate-term exposure to metsulfuron-methyl via the dietary 

and the residential pathways. Since the dermal endpoint was selected from a route-specific study 

and the toxicological effects seen by the dermal route are not the same as those seen by the oral 

route of exposure and the inhalation route, for which the POD is based on an oral study, the 

dermal and inhalation exposures are not to be combined for the aggregate exposure assessment. 

For adults, the short- and intermediate-term aggregate routes of exposure include oral (dietary, 

food, and water) and inhalation (residential handler) exposure. For children (1 to <2 years old), 

the aggregate route of exposure includes only oral (dietary and incidental oral) exposure. The 

average dietary exposure estimate for adults and children 1 < 2 years old were used to determine 

the aggregate risk estimate. As noted in Section 6.0, there are no dermal risks associated with 

the existing uses of metsulfuron-methyl. All aggregate (oral and inhalation) MOEs are greater 

than 100; therefore, aggregate exposure to metsulfuron-methyl is not of risk concern. See Table 

7.0. 

Table 7.0. Short- and Intermediate-Term Aggregate Risk Calculations. 

Population 

Short- or Intermediate-Term Scenario

LOC for 

Aggregate 

Risk1

Dietary 

exposure 

(food + 

drinking 

water)2

Residential Exposure3

Total 

Exposure 

Aggregate MOE 

(food and 

residential) Inhalation Incidental Oral 4
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Adults 

100 

0.010718 0.000028 NA 0.010746 3,200 

Children 

(1 to 2 

years old) 

0.017643 NA 0.0006 0.018243 1,900 

1 Adults and Children Level of Concern = 100 (based on inter- and intra- species uncertainty factors, each at 10X). 

2 Dietary exposure (mg/kg/day) = chronic dietary exposure from Table 5.3. 

3 Residential exposure (incidental oral and inhalation exposure) based on recommendations from Table 6.3.1. 

4 Aggregate MOE = POD (34 mg/kg/day) ÷ Combined dose (dietary + residential, mg/kg/day). 

 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)5 and conducting cumulative risk assessments (CRA)6. The Agency has utilized 

this framework to evaluate the SUs of which [chemical name] is a member (J. D’Agostino; 

D428798; 9/9/15). 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 metsulfuron-methyl in occupational settings from handling metsulfuron-methyl products 

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

from entering treated areas after application. 

9.1 Occupational Handler Exposure/Risk Estimates 

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

used, occupational handler exposure is expected from the registered use on a variety of 

agricultural crops, on golf courses and turf, landscape plants, forestry, and ornamental trees. 

Occupational handlers are anticipated to have short-term (1-30 days) and intermediate-term (1-6 

months) dermal and inhalation exposures. Long-term exposures (more than 6 months) are not 

anticipated. The registered labels require handlers to wear baseline attire and chemical resistant 

gloves. 

Occupational Handler Exposure Data and Assumptions 

 

5

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

(USEPA, 1999) 

6

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

(USEPA, 2002) 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

Page 23 of 55

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, 

include PHED 1.1, the 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 Table7” 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 website8

. 

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. 

Note: Tree injection is not typically assessed by HED because the Agency has no exposure data 

for the tree injection application scenario. In this assessment, however, HED did assess exposure 

from mixing/loading for the tree injection scenario. Use information specific to this chemical 

was not available for this scenario; therefore, HED used available tree injection assumptions 

from a previous assessment for dinotefuran (O’Keefe, B., D378123, 2/28/2011) to represent the 

same scenario. The registered label (Reg. No. 352-766) specifies 1 ml per injection site (or 

0.00000784 lb ai/injection site) for trees as the maximum application rate. Based on assumptions 

used in the dinotefuran tree injection assessment, it is assumed that one applicator can make 600 

trunk injections per day. This assessment assumes then that the maximum amount of product 

handled would be 0.0047 lb ai/day (0.00000784 lb ai/injection hole x 600 injection holes/day) by 

one applicator.

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

occupational handlers can be found in Appendix D. 

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates 

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

occupational handlers are greater than HED’s LOC (i.e., MOEs ≥ 100) at baseline attire (no 

chemical resistant-gloves, no respirator). The dermal MOEs range from 180 to 9,700,000 and 

the inhalation MOEs range from 1,300 to 2,600,000,000. Table C.1 in Appendix C provides the 

worst-case scenarios for the registered uses for metsulfuron-methyl.

9.2 Occupational Post-Application Dermal Exposure/Risk Estimates 

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

for metsulfuron-methyl. In accordance with 40 CFR Part 158, Dislodgeable Foliar Residue 

 

7

 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf 8

 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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(DFR) data are required for all occupational (e.g., crop, nursery, greenhouse use sites) or 

residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses 

that could result in post-application exposure to foliage. 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. 

The short- and intermediate-term post-application exposure scenarios associated with the highest 

uses for metsulfuron-methyl are summarized in Table C.2 in Appendix C. All scenarios resulted 

in MOEs greater than the LOC of 100 (ranging from 410 to 51,000) on day 0 (12 hours after 

application); and, therefore, are not of concern to HED. Table C.2. provides the worst-case 

scenarios for the registered uses for metsulfuron-methyl. 

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

metsulfuron-methyl 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 = 410 compared to the LOC of 100), 

EPA is waiving the 40 CFR Part 158 DFR data. In this instance, it is unlikely that chemicalspecific 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 metsulfuron-methyl. 

Since the estimated occupational post-application exposure for sod farms using default TTR 

values for metsulfuron-methyl is minimal in comparison to the level of concern (i.e., the 

calculated MOE is greater than 10 times higher than the level of concern, MOE = 42,000 

compared to the LOC of 100); EPA is waiving the 40 CFR TTR 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 turf transferrable residues for metsulfuron-methyl. 

9.3 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 Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The agency 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-HQOPP-2014-0219). During Registration Review, the agency will utilize this analysis to determine 

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

required for metsulfuron-methyl. 

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 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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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 

Metsulfuron-methyl is classified as Toxicity Category III via the dermal route, Toxicity Category 

IV for skin irritation potential, and Toxicity Category I for primary eye irritation. It is not a skin 

sensitizer. Upon review of the criteria for the active ingredient only, it appears that metsulfuronmethyl 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 metsulfuron-methyl.

10.0 Public Health and Pesticide Epidemiology Data 

The OPP Incident Data System (IDS), the Centers for Disease Control and Prevention/National 

Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System 

for Occupational Risk-Pesticides (SENSOR) databases were consulted for pesticide incident data 

on the active ingredient metsulfuron-methyl (K.Oo, 5/25/2011, D389637). In Aggregate IDS 

and Main IDS, from January 1, 2006 to June 6, 2011 there were 37 incidents (Aggregate IDS) 

and no incidents (Main IDS) involving metsulfuron-methyl. Upon review of these incidents, it 

was concluded that “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.” An IDS analysis 

was conducted from January 2011 to May 26, 2015; 1 incident (Main IDS) and 19 incidents 

(Aggregate IDS), and 2 incidents (SENSOR) were reported for metsulfuron-methyl. 

Metsulfuron-methyl is not included in the Agricultural Health Study (AHS), and therefore this 

study does not provide information for this report. The Agency will continue to monitor the 

incident information and if a concern is triggered, additional analysis will be included in the risk 

assessment. 

11.0 Literature References 

A literature search was performed for metsulfuron-methyl. The search did not reveal 

information that would impact the current risk assessment. 

12.0 References 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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Author Barcode Date Title 

C. Smith, S. 

Piper, 

M. Hawkins, 

S. Dapson

D389257 8/30/2011 Metsulfuron-methyl: Registration Review Scoping Document in 

Support for Human Health Assessments 

K. Oo D389637 5/25/2011 Metsulfuron-methyl: Review of Human Incidents 

G. Orrick D427429 8/12/15 Drinking Water Exposure Assessment for the Registration Review 

of 22 Sulfonylurea Herbicides

K. Rury D412018 

and 

D412408 

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. 

D. Smegal TXR # 

0055652

3/13/2012 Metsulfuron-methyl: Summary of Hazard and Science 

Policy Council (HASPOC) Meetings of March 8, 2012: 

Recommendations on the need for a 28-day inhalation, and 

the neurotoxicity battery (acute and subchronic neurotoxicity 

studies). 

Appendix A. Toxicology Data Requirements and Toxicology Profile 

Table A.1. Metsulfuron-methyl 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 21/28-Day Dermal ........................................................ 

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

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

yes 

yes 

yes 

no 

yes 

yes 

yes 

yes 

--- 

Waived1

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

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

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

yes 

yes 

yes 

yes 

yes 

yes 

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

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

870.4200a Carcinogenicity (rat) ..................................................... 

870.4200b Carcinogenicity (mouse) ............................................... 

870.4300 Chronic Toxicity/Carcinogenicity (rodent) ................... 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

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

870.5300 Mutagenicity—Gene Mutation - mammalian ............... 

yes 

yes 

yes 

yes 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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Table A.1. Metsulfuron-methyl Data Requirements 

Test Technical 

Required Satisfied 

870.5375 Mutagenicity—Structural Chromosomal Aberrations .. 

870.5385 Mutagenicity—Structural Chromosomal Aberrations .. 

870.5395 Mutagenicity—Other Genotoxic Effects ...................... 

870.5550 Mutagenicity—Other Genotoxic Effects ...................... 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

yes 

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

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

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

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

870.6300 Developmental Neurotoxicity ....................................... 

no 

no 

yes 

yes 

no 

--- 

--- 

Waived1

Waived1

--- 

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

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

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

yes 

no 

yes 

yes 

--- 

Waived1

1 Data requirement waived by HASPOC for the 90-day inhalation, acute/subchronic neurotoxicity, and immunotoxicity studies 

(TXR#0055652 and TXR#0056723). 

 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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A.2. Toxicity Profiles 

Table A.2.1. Metsulfuron-methyl Acute Toxicity Profile

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

870.1100 Acute oral – rat 

94.9% a.i. 

42545901 LD50 > 3000 

mg/kg (HDT) 

III 

870.1200 Acute dermal - rabbit 

92.9% a.i. 

00125828 LD50 > 2000 

mg/kg (ODT) 

III 

870.1300 Acute inhalation - rat 

92.9% a.i. 

00125830 LC50 > 5.3 

mg/L/4hr (dust 

inhalation) 

IV 

870.2400 Acute eye irritation –rabbit 

95% a.i. 

40357801 Moderate to 

severe irritation 

I 

870.2500 Acute dermal irritation – rabbit 

95.8% a.i. 

40858802 

42559604 

Non-irritating IV 

870.2600 Skin sensitization – guinea pig 

95.8% a.i. 

40858803 

42559600 

Negative dermal 

sensitizer 

N/A 

Table A2.2. Metsulfuron-methyl Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 13-Week feeding – 

rat 

125834 (1982) 

Acceptable/ non-guideline 

0, 100, 100, 7500 ppm 

NOAEL: 1000 ppm (64 mg/kg/day) 

LOAEL: 7500 ppm (659 mg/kg/day) based on 

significant decreases in body weight in females. 

870.3200 21/28-Day dermal 

toxicity - rabbit 

40357803 (1987) 

41247801 (1989) 

Acceptable/ guideline 

0, 125, 500, 2000 

mg/kg/day 

Dermal NOAEL: 125 mg/kg/day 

Dermal LOAEL: 500 mg/kg/day (skin lesions 

characterized by diffuse/multifocal dermatitis 

Systemic NOAEL: 125 mg/kg/day 

Systemic LOAEL: 500 mg/kg/day based on 

increased incidence of diarrhea. 

870.3700 Prenatal 

developmental in 

the rat 

125835 (1982) 

Acceptable/ guideline 

0, 40, 250 and 100 

mg/kg/day 

Maternal NOAEL: 250 mg/kg/day 

Maternal LOAEL: 1000 mg/kg/day based on 

salivation and decreased body weight gain - 

compensatory increase after dosing stopped. 

Developmental NOAEL: 1000 mg/kg/day 

(HDT) 

Developmental LOAEL: not determined 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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Table A2.2. Metsulfuron-methyl Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3700 Prenatal 

developmental in 

the rabbit 

125836 (1982) 

Acceptable/ guideline 

0, 25, 100, 300, 700 

mg/kg/day 

Maternal NOAEL: 25 mg/kg/day 

Maternal LOAEL: 100 mg/kg/day based on 

increased mortality, decreased body weight 

gains, and clinical signs of anorexia, red/orange 

urine and/or exudate. 

Developmental NOAEL: 700 mg/kg/day 

(HDT) 

 Developmental LOAEL: not established 

870.3800 Reproduction and 

fertility effects in 

the rat 

00151028 (1985) 

Acceptable/ guideline 

0, 25, 500 and 5000 ppm 

Parental systemic NOAEL: 500 ppm [34/43 

mg/kg/day (M/F)] 

Parental systemic LOAEL: 5000 ppm [342/475 

mg/kg/day (M/F)] based on decreased 

premating body weight in F0 males and 

females. 

Offspring/Reproductive NOAEL: (5000 ppm) 

342/475 mg/kg/day (M/F) 

Offspring/Reproductive LOAEL: not 

determined 

870.4100 Chronic oral 

toxicity in the dog 

141821 (1984) 

Acceptable/ guideline 

0, 50, 500 or 5000 ppm 

NOAEL: (5000 ppm) 125 mg/kg/day (M/F) at 

the HDT 

LOAEL: not determined 

870.4300 Carcinogenicity in 

the mouse by the 

oral route 

151135 (1985) 

Acceptable/ non-guideline 

0, 5, 25, 500, 5000 ppm 

NOAEL: 5000 ppm (666/836 mg/kg/day) 

(M/F) at the HDT 

LOAEL: not determined. 

No evidence of carcinogenic potential of the 

test material. 

870.4500 Combined Chronic/ 

Carcinogenicity in 

the rat by the oral 

route 

154477 (1985) 

Acceptable/ guideline 

0, 5, 25, 500, and 5000 

ppm 

NOAEL: 500 ppm (25 mg/kg/day) in M/F 

LOAEL: 5000 ppm (250 mg/kg/day) based on 

decreased body weight in males and females 

No evidence of carcinogenic potential of the 

test material. 

870.5100 Salmonella 

typhimurium, 

Ames assay 

125837 (1980) 

Acceptable/guideline 

Not mutagenic under the conditions of the 

study. 

870.5375 In vitro mammalian 

chromosomal 

aberrations - CHO 

cells (2 studies) 

125838 (1982) 125839 

(1983) 

Acceptable/ guideline 

Metsulfuron methyl is not a clastogen under the 

conditions of the study. 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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Table A2.2. Metsulfuron-methyl Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.5385 In vivo mammalian 

chromosome 

aberrations - rat 

bone marrow 

125840 (1983) 

Acceptable/guideline 

Metsulfuron methyl did not induce a significant 

increase in chromosome aberrations in bone 

marrow cells when compared to the vehicle 

control group. 

870.5395 In vivo mammalian 

cytogenetics - 

micronucleus assay 

in mice 

41118002 (1989) 

Acceptable/guideline 

Metsulfuron methyl was negative at the limit 

dose for clastogenic activity in the 

micronucleus assay in bone marrow cells. 

870.5550 UDS assay in 

primary rat 

hepatocytes/ 

mammalian cell 

culture 

41773901 (1990) 

42545801 (1990) 

43035601 (1993) 

Acceptable/ guideline 

Metsulfuron methyl was negative for UDS in 

mammalian hepatocytes in vivo. 

870.7485 Metabolism and 

pharmacokinetics 

in the rat 

141828 (1984) 

Acceptable/ guideline 

The primary route of excretion was via the 

urine which accounted for approx. 71-95% 

among the various treatment groups. Fecal 

elimination was 4.8-13.3%. 

Tissue burdens were minimal (generally <0.1% 

to 1%) regardless of exposure protocol; the 

gastrointestinal tract, carcass, and skin had the 

highest concentrations of radioactivity 

Four metabolites and parent were recovered in 

both urine and feces in all treatment groups. 

Parent compound accounted for most of the 

urinary and fecal radioactivity (77-90% and 

1.8-6.2% of the administered dose, 

respectively). Metab. I was consistent with 

(methyl 2-[(amino)sulfonyl] benzoate); Metab. 

II - (2-[(amino)sulfonyl]-benzoic acid); and 

Metab. III was consistent with (methyl 2-

[[{(amino)carbonyl]aminoj sulfonyl] benzoate). 

Metab. I and II appeared to result from 

sequential hydrolysis reactions terminating in 

the formation of saccharin while Metab. III was 

formed by cleavage of the two ring structures. 

Total metabolites (in urine + feces of each 

group) accounted for approximately 5.4-8.2% 

of the administered dose. The metabolite 

profiles were qualitatively similar for urine and 

feces in the parent compound and the four 

metabolites (saccharin, Metabolites I, II, and 

III) were found in both matrices. 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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Appendix B. 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. 

 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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Appendix C. Occupational Short-term/Intermediate-term Handler Exposure and Risk 

Estimates for Metsulfuron-methyl. 

Table C.1. Occupational Short-term/Intermediate-term Handler Exposure and Risk Estimates for 

Metsulfuron-methyl.

Exposure 

Scenario 

Crop or 

Target1 

Baseline 

Dermal 

Unit 

Exposure 2 

(μg/lb ai) 

Baseline 

Inhalation 

Unit 

Exposure2

(μg/lb ai)

Max.

Appl. 

Rate3

Area 

Treated 

or 

Amount 

Handled 

Daily4

Baseline Dermal Baseline Inhalation 

Dose5

(mg/kg/day)

MOE6

(LOC = 

100) 

Dose5

(mg/kg/day) 

MOE6

(LOC = 100) 

Mixer/Loader

M/L 

WDG/DF for 

Aerial 

Application 

Sod 227 8.96 0.04 lb 

ai/A 350 acres 0.0398 3,100 0.00156 22,000 

M/L 

WDG/DF for 

Aerial 

Application 

High-acreage 

field crops 227 8.96 0.125 

lb ai/A

1,200 

acres 

0.426 290 0.0168 2,000 

M/L 

WDG/DF for 

Aerial 

Application 

Forestry 227 8.96 0.2 lb 

ai/A 

1,200 

acres 0.681 180 0.0269 1,300

M/L 

WDG/DF for 

Chemigation 

Application 

Sod 227 8.96 0.04 lb 

ai/A 350 acres 0.0398 3,100 0.00156 22,000 

M/L 

WDG/DF for 

Chemigation 

Application 

High-acreage 

field crops 227 8.96 0.125 

lb ai/A 350 acres 0.124 1,000 0.0049 6,900 

M/L 

WDG/DF for 

Groundboom 

Application

Golf course 

(tees and 

greens only)

227 8.96 0.04 lb 

ai/A 5 acres 0.000568 220,000 0.0000224 1,500,000 

M/L 

WDG/DF for 

Groundboom 

Application 

Golf course 

(fairways, 

tees, greens) 

227 8.96 0.04 lb 

ai/A 40 acres 0.00454 28,000 0.000179 190,000 

M/L 

WDG/DF for 

Groundboom 

Application 

Sod 227 8.96 0.04 lb 

ai/A 80 acres 0.00908 14,000 0.000359 95,000 

M/L 

WDG/DF for 

Groundboom 

Application 

High-acreage 

field crops 227 8.96 0.125 

lb ai/A 200 acres 0.071 1,800 0.0028 12,000 

M/L Liquids 

for Aerial 

Application 

Sod 220 0.219 0.04 lb 

ai/A 350 acres 0.0385 3,200 0.0000384 890,000

M/L Liquids 

for Aerial 

Application 

High-acreage 

field crops 220 0.219 0.125 lb ai/A

1,200 

acres 0.413 300 0.000411 83,000 

M/L Liquids 

for Aerial 

Application 

Forestry 220 0.219 0.2 lb 

ai/A 

1,200 

acres 0.66 190 0.000658 52,000

M/L Liquids 

for 

Chemigation 

Application 

Sod 220 0.219 0.04 lb 

ai/A 350 acres 0.0385 3,200 0.0000384 890,000 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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Table C.1. Occupational Short-term/Intermediate-term Handler Exposure and Risk Estimates for 

Metsulfuron-methyl.

Exposure 

Scenario 

Crop or 

Target1 

Baseline 

Dermal 

Unit 

Exposure 2 

(μg/lb ai) 

Baseline 

Inhalation 

Unit 

Exposure2

(μg/lb ai)

Max.

Appl. 

Rate3

Area 

Treated 

or 

Amount 

Handled 

Daily4

Baseline Dermal Baseline Inhalation 

Dose5

(mg/kg/day)

MOE6

(LOC = 

100) 

Dose5

(mg/kg/day) 

MOE6

(LOC = 100) 

M/L Liquids 

for 

Chemigation 

Application 

High-acreage 

field crops 220 0.219 0.125 

lb ai/A 350 acres 0.12 1,000 0.00012 280,000 

M/L Liquids 

for 

Groundboom 

Application 

Golf course 

(tees and 

greens only) 

220 0.219 0.04 lb 

ai/A 5 acres 0.00055 230,000 0.000000548 62,000,000 

M/L Liquids 

for 

Groundboom 

Application 

Golf course 

(fairways, 

tees, greens) 

220 0.219 0.04 lb 

ai/A 40 acres 0.0044 28,000 0.00000438 7,800,000 

M/L Liquids 

for 

Groundboom 

Application 

Sod 220 0.219 0.04 lb 

ai/A 80 acres 0.0088 14,000 0.00000876 3,900,000 

M/L Liquids 

for 

Groundboom 

Application 

High-acreage 

field crops 220 0.219 0.125 

lb ai/A 200 acres 0.0688 1,800 0.0000685 500,000 

M/L Liquids 

for Tree 

Injection 

Trees 220 0.219 

0.0047 

lb 

ai/day

1 day 0.0000129 9,700,000 0.0000000129 2,600,000,000 

Applicator

Applying 

Sprays for 

Aerial 

Application 

Sod 2.08 

(EC) 0.0049 0.04 lb 

ai/A 350 acres 0.000364 340,000 0.000000858 40,000,000 

Applying 

Sprays for 

Aerial 

Application 

High-acreage 

field crops 

2.08 

(EC) 0.0049 0.125 lb ai/A

1,200 

acres 0.0039 32,000 0.00000919 3,700,000 

Applying 

Sprays for 

Aerial 

Application 

Forestry 2.08 

(EC) 0.0049 0.2 lb ai/A 

7,500 

acres 0.039 3,200 0.0000919 370,000 

Applying 

Sprays for 

Groundboom 

Application 

Golf course 

(tees and 

greens only) 

78.6 0.34 0.04 lb 

ai/A 5 acres 0.000196 640,000 0.00000085 40,000,000 

Applying 

Sprays for 

Groundboom 

Application 

Golf course 

(fairways, 

tees, greens) 

78.6 0.34 0.04 lb 

ai/A 40 acres 0.00158 79,000 0.0000068 5,000,000 

Applying 

Sprays for 

Groundboom 

Application 

Sod 78.6 0.34 0.04 lb 

ai/A 80 acres 0.00315 40,000 0.0000136 2,500,000 

Applying 

Sprays for 

Groundboom 

Application 

High-acreage 

field crops 78.6 0.34 0.125 lb ai/A 200 acres 0.0246 5,100 0.000106 320,000 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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Table C.1. Occupational Short-term/Intermediate-term Handler Exposure and Risk Estimates for 

Metsulfuron-methyl.

Exposure 

Scenario 

Crop or 

Target1 

Baseline 

Dermal 

Unit 

Exposure 2 

(μg/lb ai) 

Baseline 

Inhalation 

Unit 

Exposure2

(μg/lb ai)

Max.

Appl. 

Rate3

Area 

Treated 

or 

Amount 

Handled 

Daily4

Baseline Dermal Baseline Inhalation 

Dose5

(mg/kg/day)

MOE6

(LOC = 

100) 

Dose5

(mg/kg/day) 

MOE6

(LOC = 100) 

Applying 

Sprays for 

MechanicallyPressurized 

Handgun 

Application 

Rights-of-way 

(e.g., utilities, 

railroad, 

roadways) 

1,300 3.9 

0.0015 

lb 

ai/gal

1,000 

gallons 0.0244 5,100 0.0000731 470,000 

Flagger for 

Aerial 

Application 

for Liquids 

Sod 11 0.35 0.04 lb 

ai/A 350 acres 0.00193 65000 0.0000613 550,000 

Flagger for 

Aerial 

Application 

for Liquids 

High-acreage 

field crops 11 0.35 0.125 lb ai/A 350 acres 0.00601 21000 0.000191 180,000 

Mixer/Loader/Applicator

M/L/A 

WDG/DF for 

Backpack 

Application 

Rights-of-way 

(e.g., utilities, 

railroad, 

roadways) 

8,260 2.58 

0.0015 

lb ai/ 

gallon

40 

gallons 0.0062 20,000 0.00000194 18,000,000 

M/L/A 

WDG/DF for 

Backpack 

Application, 

Foliar Spray 

(Broadcast) 

Christmas 

Tree Farm 13,200 140 

0.002 

lb ai/ 

gallon

40 

gallons 0.0133 9,400 0.00014 240,000 

M/L/A 

WDG/DF for 

Backpack 

Application, 

Ground/SoilDirected 

Christmas 

Tree Farm 8,260 2.58 

0.002 

lb 

ai/gall

on 

40 

gallons 0.00826 15,000 0.00000258 13,000,000 

M/L/A 

WDG/DF for 

Backpack 

Application 

Forestry 8,260 2.58 

0.002 

lb ai/ 

gallon

40 

gallons 0.00826 15,000 0.00000258 13,000,000 

M/L/A 

WDG/DF 

with 

Backpack for 

Broadcast 

Treatment 

Landscaping, 

turf (lawns, 

athletic fields, 

parks, etc.) 

8,260 2.58 

0.0004 

lb ai/ 

gallon

40 

gallons 0.00165 76,000 0.000000516 66,000,000 

M/L/A 

WDG/DF 

with 

Backpack for 

Spot 

Treatment 

Landscaping, 

turf (lawns, 

athletic fields, 

parks, etc.) 

8,260 2.58 

0.0004 

lb ai/ 

gallon

40 

gallons 0.00165 76,000 0.000000516 66,000,000 

M/L/A 

WDG/DF 

with 

ManuallyPressurized 

Handwand 

Christmas 

Tree Farm 100,000 30 

0.002 

lb ai/ 

gallon

40 

gallons 0.1 1,300 0.00003 1,100,000 
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Table C.1. Occupational Short-term/Intermediate-term Handler Exposure and Risk Estimates for 

Metsulfuron-methyl.

Exposure 

Scenario 

Crop or 

Target1 

Baseline 

Dermal 

Unit 

Exposure 2 

(μg/lb ai) 

Baseline 

Inhalation 

Unit 

Exposure2

(μg/lb ai)

Max.

Appl. 

Rate3

Area 

Treated 

or 

Amount 

Handled 

Daily4

Baseline Dermal Baseline Inhalation 

Dose5

(mg/kg/day)

MOE6

(LOC = 

100) 

Dose5

(mg/kg/day) 

MOE6

(LOC = 100) 

M/L/A 

WDG/DF 

with 

ManuallyPressurized 

Handwand 

Landscaping, 

turf (lawns, 

athletic fields, 

parks, etc.) 

100,000 30 

0.0004 

lb ai/ 

gallon

40 

gallons 0.02 6,300 0.000006 5,700,000 

M/L/A 

WDG/DF 

with 

MechanicallyPressurized 

Handgun 

Golf course 

(tees and 

greens only) 

1,960 42 0.04 lb 

ai/A 5 acres 0.0049 26,000 0.000105 320,000 

M/L/A 

WDG/DF 

with 

MechanicallyPressurized 

Handgun 

Golf course 

(fairways, 

tees, greens) 

1,960 42 0.04 lb 

ai/A 5 acres 0.0049 26,000 0.000105 320,000 

M/L/A 

WDG/DF 

with 

MechanicallyPressurized 

Handgun 

Christmas 

Tree Farm 1,300 3.9 

0.002 

lb ai/ 

gallon

1,000 

gallons 0.0325 3,800 0.0000975 350,000 

M/L/A 

WDG/DF 

with 

MechanicallyPressurized 

Handgun 

Landscaping, 

turf (lawns, 

athletic fields, 

parks, etc.) 

1,960 42 0.04 lb 

ai/A 5 acres 0.0049 26,000 0.000105 320,000 

M/L/A 

Liquids with 

Backpack 

Rights-of-way 

(e.g., utilities, 

railroad, 

roadways) 

8,260 2.58 

0.0015 

lb ai/ 

gallon

40 

gallons 0.0062 20,000 0.00000194 18,000,000 

M/L/A 

Liquids with 

Backpack 

Christmas 

Tree Farm 13,200 140 

0.002 

lb ai/ 

gallon

40 

gallons 0.0133 9,400 0.00014 240,000 

M/L/A 

Liquids with 

Backpack,

Ground/SoilDirected 

Christmas 

Tree Farm 8,260 2.58 

0.002 

lb ai/ 

gallon

40 

gallons 0.00826 15,000 0.00000258 13,000,000 

M/L/A 

Liquids with 

Backpack 

Forestry 8,260 2.58 

0.002 

lb ai/ 

gallon

40 

gallons 0.00826 15,000 0.00000258 13,000,000 

M/L/A 

Liquids with 

Backpack for 

Broadcast 

Treatment 

Landscaping, 

turf (lawns, 

athletic fields, 

parks, etc.) 

8,260 2.58 

0.0004 

lb ai/ 

gallon

40 

gallons 0.00165 76,000 0.000000516 66,000,000 

M/L/A 

Liquids with 

Backpack for 

Landscaping, 

turf (lawns, 

athletic fields, 

parks, etc.) 

8,260 2.58 

0.0004 

lb ai/ 

gallon

40 

gallons 0.00165 76,000 0.000000516 66,000,000 
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Table C.1. Occupational Short-term/Intermediate-term Handler Exposure and Risk Estimates for 

Metsulfuron-methyl.

Exposure 

Scenario 

Crop or 

Target1 

Baseline 

Dermal 

Unit 

Exposure 2 

(μg/lb ai) 

Baseline 

Inhalation 

Unit 

Exposure2

(μg/lb ai)

Max.

Appl. 

Rate3

Area 

Treated 

or 

Amount 

Handled 

Daily4

Baseline Dermal Baseline Inhalation 

Dose5

(mg/kg/day)

MOE6

(LOC = 

100) 

Dose5

(mg/kg/day) 

MOE6

(LOC = 100) 

Spot 

Treatment 

M/L/A 

Liquids with 

ManuallyPressurized 

Handwand 

Christmas 

Tree Farm 100,000 30 

0.002 

lb ai/ 

gallon

40 

gallons 0.1 1,300 0.00003 1,100,000 

M/L/A 

Liquids with 

ManuallyPressurized 

Handwand 

Landscaping, 

turf (lawns, 

athletic fields, 

parks, etc.) 

100,000 30 

0.0004 

lb ai/ 

gallon

40 

gallons 0.02 6,300 0.000006 5,700,000 

M/L/A 

Liquids with 

MechanicallyPressurized 

Handgun 

Golf course 

(tees and 

greens only) 

1,140 1.9 0.04 lb 

ai/A 5 acres 0.00285 44,000 0.00000475 7,200,000 

M/L/A 

Liquids with 

MechanicallyPressurized 

Handgun 

Golf course 

(fairways, 

tees, greens) 

1,140 1.9 0.04 lb 

ai/A 5 acres 0.00285 44,000 0.00000475 7,200,000 

M/L/A 

Liquids with 

MechanicallyPressurized 

Handgun 

Christmas 

Tree Farm 1,300 3.9 

0.002 

lb ai/ 

gallon

1,000 

gallons 0.0325 3,800 0.0000975 350,000 

M/L/A 

Liquids with 

MechanicallyPressurized 

Handgun 

Landscaping, 

turf (lawns, 

athletic fields, 

parks, etc.) 

1,140 1.9 0.04 lb 

ai/A 5 acres 0.00285 44,000 0.00000475 7,200,000 

1 “High-acreage field crops” include sugarcane. The worst-case scenarios for the registered uses for metsulfuron-methyl 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 4.1). 

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 (125 mg/kg/day) ÷ Dermal Dose (mg/kg/day). Inhalation MOE = Inhalation NOAEL (34 mg/kg/day) ÷ 

Inhalation Dose (mg/kg/day). 

7 Total MOE = NOAEL (10 mg/kg/day) ÷ Dermal Dose + Inhalation Dose. 

Table C.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Metsulfuron-methyl.

Crop/Site Activities 

Transfer 

Coefficient 

(cm2/hr) 

Application Rate 

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

Short- and Intermediate-term

Christmas Tree Grading, Tagging, 

Hand Weeding 100 

0.15 0.42 

0.004 30,000 

Christmas Tree Transplanting 230 0.010 13,000 
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Table C.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Metsulfuron-methyl.

Crop/Site Activities 

Transfer 

Coefficient 

(cm2/hr) 

Application Rate 

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

Short- and Intermediate-term

Christmas Tree Scouting, Shaping 580 0.024 5,100 

Christmas Tree Hand Harvesting 1,400 0.059 2,100 

Christmas Tree Hand Set Irrigation 1,900 0.080 1,600 

Forestry Hand Weeding 100 

0.2 

0.42 

0.004 30,000 

Forestry Transplanting 230 0.010 13,000 

Forestry Scouting, Hand 

Pruning 580 0.024 5,100 

Forestry 

Seed Cone 

Harvesting 

(Conifers) 

1,400 0.059 2,100 

Forestry Hand Set Irrigation 1,900 0.080 1,600 

Forestry 

Seedling 

Production 

Harvesting 

6,700 0.017 0.011 11,000 

Sod 

Maintenance, 

Harvesting, Slab, 

Transplanting, 

Harvesting, Roll 

6,700 0.04 0.004 0.003 42,000 

Sugarcane Hand Weeding 70 

0.125 0.35 

0.002 51,000 

Sugarcane Scouting 1,100 0.039 3,200 

Sugarcane Hand Harvesting 8,800 0.039 410 

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). 

 
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Appendix D. Summary of Occupational and Residential 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). 

Occupational Non-Cancer Post-application Algorithms 
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Potential daily exposures for occupational post-application workers are calculated using the 

following formulas: 

DFRt=AR * F* (1-D)t* ቀ4.54E8 ug

lbቁ * ൬2.47E-8

A

cm2൰

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: 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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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). 

Residential Non-Cancer Handler Algorithms 

Dermal and Inhalation Handler Exposure Algorithm - Turf 

Daily dermal and inhalation exposure (mg/day) for residential pesticide handlers, for a given 

formulation-application method combination, is estimated by multiplying the formulationapplication method-specific unit exposure by an estimate of the amount of active ingredient 

handled in a day, using the equation below: 

E = UE * AR * A 

where: 

E = exposure (mg/day); 

UE = unit exposure (mg/lb ai); 

AR = application rate (e.g., lb ai/ft2

, lb ai/gal); and 

A = area treated or amount handled (e.g., ft2

/day, gal/day). 

Dermal and/or inhalation absorbed doses normalized to body weight are calculated as: 

D = E *AF / BW 

where: 

D = dose (mg/kg-day); 

E = exposure (mg/day); 

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

BW = body weight (kg). 

Residential Non-Cancer Post-Application Algorithms 

Post-application Dermal Exposure Algorithm – Physical Activities on Turf 

Exposure resulting from contacting previously treated turf while performing physical activities is 

calculated as shown below. Residential post-application exposure assessment must include 

calculation of exposure on the day of application. Therefore, though an assessment can present 

exposures for any day “t” following the application, it must include “day 0” exposure. 

E = TTRt * CF1 * TC * ET

where: 

E = exposure (mg/day); 

TTRt = turf transferable residue on day t (μg/cm2

); 

CF1 = weight unit conversion factor (0.001 mg/μg); 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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TC = transfer coefficient (cm2

/hr); and 

ET = exposure time (hr/day). 

If chemical-specific TTR data are available, then surface residues from the day of application 

should be used (assume that individuals could be exposed to residues immediately after 

application). However, if data are not available, then TTRt can be calculated using the following 

formula: 

TTRt= AR * F * (1-FD)t * CF2 * CF3

where: 

TTRt = turf transferable residue on day t (μg/cm2

); 

AR = application rate (lbs ai/ft2

 or lb ai/acre); 

F = fraction of ai as transferable residue following application (unitless); 

FD = fraction of residue that dissipates daily (unitless); 

t = post-application day on which exposure is being assessed; 

CF2 = weight unit conversion factor (4.54 x 108 μg/lb); and 

CF3 = area unit conversion factor (1.08 x 10-3 ft2/ cm2 or 2.47 x 10-8 acre/cm2). 

Dermal absorbed doses are calculated as: 

BW

E AF D* 

 

where: 

D = dose (mg/kg-day); 

E = exposure (mg/day); 

AF = absorption factor (dermal); and 

BW = body weight (kg).

Table D-1: Turf (Physical Activities) -- Inputs for Residential Post-application Dermal Exposure 

Algorithm Notation Exposure Factor 

(units) Point Estimate(s) 

AR Application rate 

(mass active ingredient per unit area) See table 3.2. 

F 

Fraction of AR as TTR 

following application (if 

chemical-specific data is 

unavailable) 

L/WP/WDG 0.01 

Granules 0.002 

FD

Daily residue dissipation (if 

chemical-specific data is 

unavailable) 

(fraction) 

L/WP/WDG 0.1 

Granules 0.1 

TC 

Transfer 

Coefficient 

(cm2/hr) 

L/WP/WDG Adults 180,000 

Children 1 < 2 years old 49,000 

Granules Adults 200,000 

Children 1 < 2 years old 54,000 

ET Exposure Time 

(hours per day) 

Adults 1.5 

Children 1 < 2 years old 1.5 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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Table D-1: Turf (Physical Activities) -- Inputs for Residential Post-application Dermal Exposure 

Algorithm Notation Exposure Factor 

(units) Point Estimate(s) 

BW Body Weight 

(kg) 

Adults 80 

Children 1 < 2 years old 11 

L/WP/WDG = Liquids/Wettable Powders/Water-dispersible Granules 

Post-application Hand-to-Mouth Exposure Algorithm– Physical Activities on Turf 

Exposure from hand-to-mouth activity is calculated as follows (based on the algorithm utilized in 

the SHEDS-Multimedia model): 

E = [HR * (FM * SAH) * (ET * N_Replen) * (1- (1- SE)(Freq_HtM/N-Replen))]

where: 

E = exposure (mg/day); 

HR = hand residue loading (mg/cm2

); 

FM = fraction hand surface area mouthed / event (fraction/event); 

SAH = typical surface area of one hand (cm2); 

ET = exposure time (hr/day); 

N_Replen = number of replenishment intervals per hour (intervals/hour); 

SE = saliva extraction factor (i.e., mouthing removal efficiency); and 

Freq_HtM = number of hand-to-mouth contacts events per hour (events/hour). 

and 

SA *2

Fai *DE

HR

H

hands 

 

where: 

HR = hand residue loading (mg/cm2

); 

Faihands = fraction ai on hands compared to total surface residue from dermal transfer coefficient 

study (unitless); 

DE = dermal exposure (mg); and 

SAH = typical surface area of one hand (cm2

). 

Dose, normalized to body weight, is calculated as: 

BW

E D 

 

where: 

D = dose (mg/kg-day); 

E = exposure (mg/day); and 

BW = body weight (kg). 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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Table D-2: Turf (Physical Activities) – Inputs for Residential Post-application Hand-to-Mouth Exposure 

Algorithm 

Notation 

Exposure Factor 

(units) Point Estimate(s) 

Faihands

Fraction of ai on hands from 

dermal transfer coefficient 

study 

(unitless) 

Liquid formulations 0.06 

Granular formulations 0.027 

DE Dermal exposure (mg) Calculated 

SAH Typical surface area of one hand (cm2), children 1 < 2 

years old 150 

AR Application rate 

(mass active ingredient per unit area) See table 3.2. 

HR Residue available on the hands (mg/cm2) Calculated via (DE * Faihands)/SAH

FM Fraction hand surface area mouthed 

(fraction/event) 0.127 

N_Replen Replenishment intervals per hour 

(intervals/hr) 4 

ET Exposure time 

(hrs/day) 1.5 

SE Saliva extraction factor 

(unitless) 0.48 

Freq_HtM Hand-to-mouth events per hour 

(events/hr) 13.9 

BW Body Weight 

(kg) Children 1 < 2 years old 11 

Post-application Object-to-Mouth Exposure Algorithm– Physical Activities on Turf 

Exposure from object-to-mouth activity is calculated as follows (based on the algorithm utilized 

in SHEDS-Multimedia):

E = [OR* CF1 * SAMO * (ET * N_Replen) * (1- (1- SEO)

(Freq_OtM/N_Replen))] 

where: 

E = exposure (mg/day); 

OR = chemical residue loading on the object on day “t” (ug/cm2); 

CF1 = weight unit conversion factor (0.001 mg/μg); 

SAMO = area of the object surface that is mouthed (cm2

/event); 

ET = exposure time (hr/day); 

N_Replen = number of replenishment intervals per hour (intervals/hour); 

SEO = saliva extraction factor (i.e., mouthing removal efficiency); and 

Freq_OtM = number of object-to-mouth contact events per hour (events/hour). 

and 

OR = AR * FO * CF2 * CF3 

where: 

OR = chemical residue loading on the object (μg/cm2

); 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

Page 44 of 55

AR = application rate (lbs ai/ft2

 or lb ai/acre); 

FO = fraction of residue available on the object (unitless); 

CF2 = weight unit conversion factor (4.54 x 108 μg/lb); and 

CF3 = area unit conversion factor (1.08 x 10-3 ft2/cm2 or 2.47 x 10-8 acre/cm2). 

Dose, normalized to body weight, is calculated as: 

BW

E D 

 

where: 

D = dose (mg/kg-day); 

E = exposure (mg/day); and 

BW = body weight (kg). 

Table D-3: Turf (Physical Activities) – Inputs for Residential Post-application Object-to-Mouth Exposure 

Algorithm 

Notation 

Exposure Factor 

(units) Point Estimate(s) 

AR Application rate (to turf) 

(mass active ingredient per unit area) See table 3.2. 

FO Fraction of AR as OR following application 1 0.01 

SAMO Surface area of object mouthed 

(cm2/event) 10 

N_Replen Replenishment intervals per hour (intervals/hour) 4 

SEO Saliva extraction factor 

(fraction) 0.48 

ET Exposure time 

(hours per day) 1.5 

Freq_OtM Object-to-mouth events per hour (events/hr) 8.8 

BW Body Weight (kg) Children 1 < 2 years old 11 

1 This SOP assumes that all of the residue on the turf could be transferred to the object (e.g., object residue is equal to turf 

transferable residue). 

Post-application Incidental Soil Ingestion Exposure Algorithm– Physical Activities on Turf 

Exposure from incidental soil ingestion is calculated as follows:

E = SRt * SIgR * CF1 

where: 

E = exposure (mg/day); 

SRt = soil residue on day "t" (μg/g); 

SIgR = ingestion rate of soil (mg/day); and 

CF1 = weight unit conversion factor (1 x 10-6 g/μg). 

and 

SRt = AR * FS * (1-FD)

t

 * CF2 * CF3 * CF4 

where: 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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SRt = soil residue on day "t" (μg/g); 

AR = application rate (lbs ai/ft2 or lb ai/acre); 

FS = fraction of ai available in uppermost cm of soil (fraction/cm); 

FD = fraction of residue that dissipates daily (unitless); 

T = post-application day on which exposure is being assessed; 

CF2 = weight unit conversion factor (4.54 x 108

 μg/lb); 

CF3 = area unit conversion factor (1.08 x 10-3 ft2/cm2 or 2.47 x 10-8 acre/cm2); and 

CF4 = soil volume to weight unit conversion factor (0.67 cm3

/g soil). 

Dose, normalized to body weight, are calculated as: 

BW

E D 

 

where: 

 D = dose (mg/kg-day); 

 E = exposure (mg/day); and 

 BW = body weight (kg). 

Table D-4: Turf (Physical Activities) – Inputs for Residential Post-application Incidental Soil Ingestion Exposure 

Algorithm 

Notation 

Exposure Factor 

(units) Point Estimate(s) 

AR Application rate 

(mass active ingredient per unit area) See table 3.2. 

FS Fraction of AR available in uppermost 1 cm of soil 

(unitless) 1 

FD Daily residue dissipation 

(fraction) 0.1 

SIgR Soil ingestion rate (mg/day) 50 

BW Body weight (kg) Children 1 < 2 years old 11 

Post-application Episodic Granular Ingestion Exposure Algorithm– Physical Activities on Turf 

Exposure from incidental ingestion of pesticide pellets or granules is calculated as follows: 

 E = GIgR* FD * CF1 

where: 

E = exposure (mg/day); 

GIgR = ingestion rate of dry pesticide formulation (g/day); 

FD = fraction of ai in dry formulation (unitless); and 

CF1 = weight unit conversion factor (1,000 mg/g). 

Dose, normalized to body weight, are calculated as: 

BW

E D 

 where: 

 D = dose (mg/kg-day); 
Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414 

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 E = exposure (mg/day); and 

BW = body weight (kg). 

Table D-5: Turf (Physical Activities) – Inputs for Residential Post-application Episodic Granular Ingestion 

Exposure 

Algorithm 

Notation 

Exposure Factor 

(units) Point Estimate(s) 

FD Fraction of active ingredient in dry formulation See table 3.2 

AR Application rate (lbs/A or lbs/1,000 ft2) See table 3.2

GIgR Granule ingestion rate per day 

(g/day) 1 0.3 

BW Body Weight (kg) Children 1 < 2 years old 11 

1 See discussion below on how this value may be adjusted if product specific information is available. 

Post-application Dermal Exposure Algorithm – Mowing 

Exposure resulting from contacting previously treated turf while mowing is calculated as 

follows: 

E = TTRt * CF1 * TC * ET 

where: 

E = exposure (mg/day); 

TTRt = turf transferable residue on day "t" (μg/cm2); 

CF1 = weight unit conversion factor (0.001 mg/μg); 

TC = transfer coefficient (cm2/hr); and 

ET = exposure time (hr/day). 

and 

TTRt = AR * FAR * (1-FD)

t

 * CF2 * CF3 

where: 

TTRt = turf transferable residue on day "t" (μg/cm2

); 

AR = application rate (lbs ai/ft2

 or lb ai/acre); 

FAR = fraction of ai retained on turf (unitless); 

FD = fraction of residue that dissipates daily (unitless); 

t = post-application day on which exposure is being assessed; 

CF2= weight unit conversion factor (4.54 x 108 μg/lb); and 

CF3 = area unit conversion factor (1.08 x 10-3 ft2

/cm2 or 2.47 x 10-8 acre/cm2). 

Absorbed dose, normalized to body weight, are calculated as: 

BW

E AF D* 

 
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where: 

D = dose (mg/kg-day); 

E = exposure (mg/day); 

AF = absorption factor (dermal); and 

BW = body weight (kg). 

Table D-6: Turf (Mowing) – Inputs for Residential Post-application Dermal Exposure 

Algorithm Notation Exposure Factor 

(units) Point Estimate(s) 

AR Application rate 

mass active ingredient per unit area See table 3.2 

FAR

Fraction of AR as 

TTR following 

application 

L/WP/WDG 0.01 

Granules 0.002 

FD Daily residue 

dissipation 

L/WP/WDG 0.1 

Granules 0.1 

TC Transfer Coefficient 

(cm2/hr) 

Adult 5,500 

Children 11 < 16 years 

old 4,500 

ET Exposure time 

(hours per day) 1 

BW Body Weight 

(kg) 

Adults 80 

Children 11 < 16 years 

old 57 

L/WP/WDG = liquid/wettable powder/water dispersible granule 

Post-application Dermal Exposure Algorithm – Golfing 

Exposure resulting from contacting previously treated turf while golfing is calculated as follows: 

E = TTRt * CF1 * TC * ET 

where: 

E = exposure (mg/day); 

TTRt = turf transferable residue on day "t" (μg/cm2

); 

CF1 = weight unit conversion factor (0.001 mg/μg); 

TC = transfer coefficient (cm2

/hr); and 

ET = exposure time (hr/day). 

and 

TTRt = AR * F * (1-FD)

t

 * CF2 * CF3 

where: 

TTRt = turf transferable residue on day "t" (μg/cm2

); 

AR = application rate (lbs ai/ft2

 or lb ai/acre); 

F = fraction of ai retained on turf (unitless);’ 
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FD = fraction of residue that dissipates daily (unitless); 

t = post-application day on which exposure is being assessed; 

CF2 = weight unit conversion factor (4.54 x 108 μg/lb); and 

CF3 = area unit conversion factor (1.08 x 10-3 ft2/cm2 or 2.47 x 10-8 acre/cm2). 

Absorbed dose, normalized to body weight, is calculated as: 

BW

E AF D* 

 where: 

D = dose (mg/kg-day); 

E = exposure (mg/day); 

AF = absorption factor (dermal); and 

BW = body weight (kg). 

Table D-7: Turf (Golfing) – Inputs for Residential Post-application Dermal Exposure 

Algorithm 

Notation 

Exposure Factor 

(units) 

Point Estimate(s) 

AR Application rate 

(mass active ingredient per unit area) 

See table 3.2 

F Fraction of AR as TTR 

following application 

L/WP/WDG 0.01 

Granules 0.002 

FD Daily residue dissipation L/WP/WDG 0.1 

Granules 0.1 

TC Transfer Coefficient 

(cm2/hr) 

Adult 5,300 

Children 11 < 16 years old 4,400 

Children 6 < 11 years old 2,900 

ET Exposure time 

(hours per day) 

Pesticides used on greens, tees, and 

fairways 

4 

Pesticides used only on greens and 

tees 

1 

BW Body Weight 

(kg) 

Adults 80 

Children 11 < 16 years old 57 

Children 6 < 11 years old 32 

NA = not applicable 

L/WP/WDG = liquid/wettable powder/water dispersible granule 

 
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Appendix E. Dietary Exposure/Risk Modeling Input and Output 

 Filename: C:\Users\jlangsda\Documents\Chemicals\SUs\Metsulfuron-methyl\Dietary 

Assessment\Metsulfuron Methyl_Chronic.r08 

Chemical: Metsulfuron-methyl 

RfD(Chronic): .25 mg/kg bw/day NOEL(Chronic): 25 mg/kg bw/day 

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

Date created/last modified: 03-26-2015/16:00:10 Program ver. 3.16, 03-08-d 

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

 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 

1500344000 15 Sorghum, grain 0.100000 1.000 1.000 

1500345000 15 Sorghum, syrup 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 0.100000 1.000 1.000 

3100044001 31 Beef, meat-babyfood 0.100000 1.000 1.000 

3100045000 31 Beef, meat, dried 0.100000 1.920 1.000 

3100046000 31 Beef, meat byproducts 0.100000 1.000 1.000 

3100046001 31 Beef, meat byproducts-babyfood 0.100000 1.000 1.000 

3100047000 31 Beef, fat 0.100000 1.000 1.000 

3100047001 31 Beef, fat-babyfood 0.100000 1.000 1.000 

3100048000 31 Beef, kidney 0.500000 1.000 1.000 

3100049000 31 Beef, liver 0.100000 1.000 1.000 

3100049001 31 Beef, liver-babyfood 0.100000 1.000 1.000 

3200169000 32 Goat, meat 0.100000 1.000 1.000 

3200170000 32 Goat, meat byproducts 0.100000 1.000 1.000 

3200171000 32 Goat, fat 0.100000 1.000 1.000 

3200172000 32 Goat, kidney 0.500000 1.000 1.000 

3200173000 32 Goat, liver 0.100000 1.000 1.000 

3300189000 33 Horse, meat 0.100000 1.000 1.000 

3400290000 34 Pork, meat 0.100000 1.000 1.000 

3400290001 34 Pork, meat-babyfood 0.100000 1.000 1.000 

3400291000 34 Pork, skin 0.100000 1.000 1.000 

3400292000 34 Pork, meat byproducts 0.100000 1.000 1.000 

3400292001 34 Pork, meat byproducts-babyfood 0.100000 1.000 1.000 

3400293000 34 Pork, fat 0.100000 1.000 1.000 

3400293001 34 Pork, fat-babyfood 0.100000 1.000 1.000 

3400294000 34 Pork, kidney 0.500000 1.000 1.000 

3400295000 34 Pork, liver 0.100000 1.000 1.000 

3500339000 35 Sheep, meat 0.100000 1.000 1.000 

3500339001 35 Sheep, meat-babyfood 0.100000 1.000 1.000 

3500340000 35 Sheep, meat byproducts 0.100000 1.000 1.000 

3500341000 35 Sheep, fat 0.100000 1.000 1.000 

3500341001 35 Sheep, fat-babyfood 0.100000 1.000 1.000 

3500342000 35 Sheep, kidney 0.500000 1.000 1.000 

3500343000 35 Sheep, liver 0.100000 1.000 1.000 

3600222000 36 Milk, fat 0.050000 1.000 1.000 

3600222001 36 Milk, fat-baby food/infant formu 0.050000 1.000 1.000 

3600223000 36 Milk, nonfat solids 0.050000 1.000 1.000 

3600223001 36 Milk, nonfat solids-baby food/in 0.050000 1.000 1.000 

3600224000 36 Milk, water 0.050000 1.000 1.000 

3600224001 36 Milk, water-babyfood/infant form 0.050000 1.000 1.000 

3600225001 36 Milk, sugar (lactose)-baby food/ 0.050000 1.000 1.000 

8601000000 86A Water, direct, all sources 0.492000 1.000 1.000 
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8602000000 86B Water, indirect, all sources 0.492000 1.000 1.000 

9500362000 O Sugarcane, sugar 0.050000 1.000 1.000 

9500362001 O Sugarcane, sugar-babyfood 0.050000 1.000 1.000 

9500363000 O Sugarcane, molasses 0.050000 1.000 1.000 

9500363001 O Sugarcane, molasses-babyfood 0.050000 1.000 1.000 

DEEM-FCID Chronic Results File

US EPA Ver. 3.16, 03-08-d 

DEEM-FCID Chronic analysis for METSULFURON-METHYL NHANES 2003-2008 2-day 

Residue file name: C:\Users\jlangsda\Documents\Chemicals\SUs\Metsulfuron-methyl\Dietary 

Assessment\Metsulfuron Methyl_Chronic.r08 

 Adjustment factor #2 used. 

Analysis Date 05-08-2015/13:37:46 Residue file dated: 03-26-2015/16:00:10 

Reference dose (RfD, Chronic) = .25 mg/kg bw/day 

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

 Total exposure by population subgroup 

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

 Total Exposure 

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

 Population mg/kg Percent of 

 Subgroup body wt/day Rfd 

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

Total US Population 0.010929 4.4% 

Hispanic 0.010560 4.2% 

Non-Hisp-White 0.011219 4.5% 

Non-Hisp-Black 0.009035 3.6% 

Non-Hisp-Other 0.012517 5.0% 

Nursing Infants 0.009578 3.8% 

Non-Nursing Infants 0.035209 14.1% 

Female 13+ PREG 0.010199 4.1% 

Children 1-6 0.015317 6.1% 

Children 7-12 0.009635 3.9% 

Male 13-19 0.007737 3.1% 

Female 13-19/NP 0.008437 3.4% 

Male 20+ 0.010054 4.0% 

Female 20+/NP 0.011192 4.5% 

Seniors 55+ 0.010337 4.1% 

All Infants 0.027296 10.9% 

Female 13-50 0.010664 4.3% 

Children 1-2 0.017643 7.1% 

Children 3-5 0.014355 5.7% 

Children 6-12 0.010151 4.1% 

Youth 13-19 0.008090 3.2% 

Adults 20-49 0.010718 4.3% 

Adults 50-99 0.010538 4.2% 

Female 13-49 0.010655 4.3% 

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

 
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Appendix F. Nomenclature and Physical/Chemical Properties 

Table 1. Metsulfuron-methyl Nomenclature.

Compound 

Chemical Structure 

S

N

H

N

H

O

O

O

O

CH3

N

N

CH3

O

CH3

O

N

Common name AE F075736; metsulfuron-methyl 

IUPAC name 

methyl 2-(4-methoxy-6-methyl-1,3,5-triazin-2-ylcarbamoylsulfamoyl)benzoate 

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

yl)amino]carbonyl]amino]sulfonyl]benzoate 

CAS registry number 74223-64-6 

Molecular formula C14H15N5O6S 

Table 2. Metsulfuron-methyl and its Metabolites.1

 

Common Name/Chemical Name 

 

Chemical Structure 

 

Matrix 

 

Metsulfuron methyl 

 

(DPX-T6376) 

 

methyl 2-[[[[(4-methoxy-6-methyl1,3,5-triazin-2-

yl)amino]carbonyl]amino] 

sulfonyl]benzoate 

 

 

 

Plants/Poultry 

 

4-Hydroxy metsulfuron methyl

 

Metabolite A1

 

(IN-G7460) 

 

methyl 2-[[[[(4-methoxy-6-methyl1,3,5-triazin-2-

yl)amino]carbonyl]amino] 

sulfonyl] 4-hydroxybenzoate 

 

 

 

Plants 

 

Metsulfuron methyl glucose conjugate

 

Metabolite A

 

Plants 
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Table 2. Metsulfuron-methyl and its Metabolites.1

 

Common Name/Chemical Name 

 

Chemical Structure 

 

Matrix 

 

(IN-B9700) 

 

methyl 2-[[[[(4-methoxy-6-methyl1,3,5-triazin-2-

yl)amino]carbonyl]amino] 

sulfonyl]4-(β-Dglucopyranosyl)benzoate 

 

O-Desmethyl metsulfuron methyl

(IN-B5067) 

methyl 2-[[[[(4-hydroxy-6-methyl-1,3,5-

triazin-2-yl)amino]carbonyl]amino] 

sulfonyl]benzoate 

Poultry2 

1

 From Memo, W. Cutchin, 12/17/01; D279786. 

2

 There are no established tolerances for residues of metsulfuron-methyl and its metabolites in poultry commodities. 

Table 3. Physicochemical Properties of the Technical Grade Metsulfuron-methyl.

Parameter Value Reference 

Melting point/range 158 °C 

Water solubility (mg/L at 25°C) 

109 at unbuffered, pH 4.1 

270 at buffered pH 4.6 

1750 at buffered pH 5.4 

9500 at buffered pH 6.7 

Solvent solubility (mg/L at 20°C) 

0.79 in n-hexane 0.79 

580 in xylene 

2300 in ethanol 

7300 in methanol 

36000 in acetone 

121000 in methylene chloride 

Vapor pressure (@ 25°C) 2.5 X 10 -12 mm Hg 

Octanol/water partition coefficient 

Log(KOW) 0.018 
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Appendix G. 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 triasulfuron. 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.9,10 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. 

In many cases, risks are of concern when the screening level estimates for spray drift are used as 

the basis for the analysis. In order to account for this issue and to provide additional risk 

 

9

http://www.agdrift.com/ 

10 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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management options additional spray drift deposition fractions were also considered. These drift 

estimates represent plausible options based on the available pesticide labels. 
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Appendix H. Analytical Standards Summary 

Analytical reference standards for metsulfuron-methyl are currently available in EPA’s National 

Pesticide Standards Repository (NPSR) and have an expiration date of 6/21/2016; however, 

standards are not available for the 4-hydroxy metsulfuron methyl metabolite (A1; methyl 2-

[[[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino]carbonyl]amino]sulfonyl]-4-hydroxybenzoate) 

(email communication between G. Verdin and J. Van Alstine, 5/7/2015 and 5/11/2015). The 

registrant is required to maintain reasonable amounts of the reference standards in the NPSR as 

long as tolerances remain published in 40 CFR §180.428. 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 

COAs, 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 29 CFR §1910.1200.