### 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 toxi city study requirements have been waived 

### (TXR#0055652, 03113 /2 012 and TXR #0 0567 23, 08 / 06 / 2013). 2) Endpoints and points of d epar tur e hav e been se l ec ted for the incidental oral exposure scenario to assess spray drift exposure/r isk es timates. 3) The occupational and residential ri s k assessment has been updated to in corporate new science policies.



### P age 1 of SSMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 2 of 55 4) A coarse-screen estimated drinking water concentration (EDWC) was used to assess metsulfuron-methyl dietary exposure and risk.Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 3 of 55 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 Physica l/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 ........................................................................................................ 1 3 5.2 Water Residue Profile...................................................................................................... 14 5.3 Dietary Exposure and Risk Estimates............................................................................ 15 6.0 Residential (Non-Occupational) Expo sure/Risk Characterization ............................. 16 6.1 Spray Drift ................................................................................................................... ..... 18 6.1.1 Combined Risk Estimates From Lawn De position Adjacent to Applications ............ 19 6.2 Residential Bystander Post-Application Inhalation Exposure .................................... 20 6.3 Residential Risk Estimates for Us e 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 Expo sure/Risk Estimates .......................................................... 22 9.2 Occupational Post-Application Derm al Exposure/Risk Estimates ............................. 23 9.3 Occupational Post-Application Inhala tion 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 Requirem ents and Toxicology Profile ................................... 26 Appendix B. Review of Human Research ................................................................................ 31 Appendix C. Occupational Short-term/Int ermediate-term Handler Exposure and Risk Estimates for Metsulfuron-methyl. ........................................................................................... 3 2 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 De tailed Description ........................................................................ 53 Appendix H. Analytical Standards Summary ......................................................................... 55Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 4 of 55 1.0 Executive Summary

Metsulfuron-methyl is a sulfonylurea herbicide that is used to cont rol broadleaf weeds on a variety of agricultural crops, on golf courses, tu rf, landscape plants, forestry, and ornamental trees. This document addresses exposures and ri sk estimates from the registered uses of metsulfuron-methyl required dur ing Registration Review. The worst-case scenarios for the registered uses for metsulfuron-met hyl are assessed in this document.

The toxicology database for metsul furon-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 inhalati on, immunotoxicity, and neurotoxicity (acute and subchronic) studies are not required at th is 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 endp oints selected for the previous risk assessment remain the same.

The existing residue chemistry database for mets ulfuron-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 screen ing-level chronic dietary exposure and risk assessment for metsulfuron-methyl using toleran ce-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 di d not conduct an acute dietary exposure and risk assessment due to the lack of an appropriate endpoint for acute dietary asse ssment. 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 a nd 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, re sidential post-application expos ure was assessed. Dermal postapplication risks were assessed for adults, children 11 to 16 year s old, and children 1 < 2 years old. All adult and older childre n 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 year s old oral non-dietary ingestion risk from hand-to-mouth activity on treated tu rf estimates for both liquid and granular formulations MOEs range from 56,000 to 25,000,000. A quantitative spra y 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 st udies, route-specific inhalationtoxicological studies) to determine if data or further analysis is required for metsulfuron-methyl.Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 5 of 55 An aggregate assessment has been conducted fo r 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 interm ediate-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-ter m margins of exposure are not of concern to HED on the day of a pplication (i.e., MOE > the LOC of 100). The MOEs range from 410 to 51,000. Based on the Agency's current prac tices, a quantitative non -cancer occupational post-application inhalation expos ure assessment was not performe d for metsulfuron-methyl at this time. If new policies or procedures are put in to place, the Agency may revisit the need for a quantitative occupational post-application i nhalation exposure assessment for metsulfuronmethyl.

The restricted entry interval (R EI) 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 fo r the active ingredient only, it appears that metsulfuron-methyl is consiste nt with the criteria in PRN 95-3 that allow for a 4-hour REI. Note : The PR Notice also includes similar criter ia 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 mets ulfuron-methyl (40 CF R §180.428) are supported by the available residue chemistry data. Codex has not establishe d 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 fo r 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



### Page 6 of 55 hydroxybenzoate, calculated as the stoichiometr ic 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 determ ined by measuring only metsulfuron-methyl (methyl 2-[[[[(4-methoxy- 6-methyl-1,3,5-triazin-2- yl)amino]carbonyl]amino]sulfonyl]benzo ate), in or on the commodity.

2.2 Analytical Standards

An analytical standard is re quired for the 4-hydroxy metsulfur on methyl metabolite (A1), as outlined in Appendix H.

3.0 Introduction

3.1 Chemical Identity and Phys ical/Chemical Characteristics

The chemical structure and nomenclature of metsul furon-methyl and a detailed description of the physicochemical properties of metsulfur on-methyl are provided in Appendix F.

3.2 Pesticide Use Pattern and Anticipated Exposure Pathways

Metsulfuron-methyl is currently used on a variet y 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 activ e ingredient. These include water-dispersible granules (WDG)/dry flowable (DF) and granular formulations. Mo st 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 fo r indirect exposure (incidental or al and dermal) to metsulfuronmethyl related to spray drift. Homeowners and agricultural workers may be exposed (dermal and inhalation) to metsulfuron-methyl during mi xing, loading, and/or appl ying the herbicide as well as during post-ap plication activities.

Based on the use pattern for mets ulfuron, short- and intermedia te-term dermal and inhalation exposures are anticipated for occupational handler s and post-application wo rkers and short-term dermal and inhalation exposures for residen tial handlers and residential post-applicationMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 7 of 55 individuals. The metsulfuron-met hyl labels require handlers to w ear 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 app lication rate of the registered uses for metsulfuron-methyl.

Table 3.2. Summary of Regist ered 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. ForestryMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 8 of 55 Table 3.2. Summary of Regist ered 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/ft 2 ) 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/ft 2 ) 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/ft 2 ) 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.Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 9 of 55 Table 3.2. Summary of Regist ered 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 ju stice concerns, to the extent possi ble, were considered in this human health risk assessment, in accordance w ith U.S. Executive Order 12898, "Federal Actions to Address Environmental Just ice in Minority Populations an d Low-Income Populations," (http://epa.gov/complian ce/ej/resources/policy/ex ec_order_12898.pdf). As a part of every pesticide risk assessment, OPP considers a larg e 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 pa tterns are compiled by the U.S. Department of Agriculture (USDA) under the Na tional Health and Nutrition Exam ination Survey, What We Eat in America, (NHANES/WWEIA; 2003- 2008) and are used in pesticid e risk assessments for all registered food uses of a pesticide. These da ta 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 ar eas post-application are evaluate d. Further considerations are currently in development as OPP has committed re sources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietar y patterns among specific subgroups.

4.0 Hazard Identification/ToxicologyMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 10 of 55 The toxicology database for metsul furon-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 inhalati on, immunotoxicity, and neurotoxicity (acute and subchronic) studies are not required at th is 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 as sessment 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 inha lation routes of exposure. It is a severe eye irritant (Cate gory 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 sensit ive species tested. There is no evidence that metsulfuron-methyl is a developmental, reproduc tive, neurotoxic, carcinogenic, mutagenic or immunotoxic chemical. The HED Hazard Id entification Assessment Review Committee (HIARC), in accordance with the 1999 Draft Gu idance 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 dietar y feeding). The primary route of excretion is via the urine (71- 95%) followed by fecal elimination (4.8-13.3%) a nd levels remaining in the tissues are negligible.

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

The toxicity database of metsulfu ron-methyl is complete and adequa te to assess the qualitative or quantitative susceptibility in the young. There is no evidence of increased qualitative or quantitative susceptibility in th e young; there is no evidence of neurotoxicity with metsulfuron methyl; and exposure estimates are unlikely to un derestimate 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 curre nt policy and may be considered conservative. However, the current PODs are protective of the effects observed inMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 11 of 55 the metsulfuron-methyl database and any updates would not impact the overall findings of the risk assessment given the current ri sk picture for me tsulfuron-methyl.

Table 4.3.1. Metsulfuron-methyl Summary of T oxicological 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 UF A = 10x UF H =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 UF A = 10x UF H =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 UF A = 10x UF H =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 UF A = 10x UF H =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 UF A = 10x UF H =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 dos e-response data and used to mark the beginning of extrapolation to determine risk associat ed with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. L OAEL = lowest observed adverse effect le vel. UF = uncertainty factor. UF A =Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 12 of 55 extrapolation from animal to human (interspecies). UF H = 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 Occupa tional 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 UF A = 10x UF H =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 UF A = 10x UF H =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 UF A = 10x UF H =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 classifi ed as “not likely to be carcinogenic to humans.” This is based on the lack of evidence of carcinog enicity in mice and rats, no evidence of mutagenicity in acceptable studies, and the non-carcinogenic poten tial of structurally related compounds. Point of Departure (POD) = A data point or an estimated point that is derived from observed dos e-response data and used to mark the beginning of extrapolation to determine risk associat ed with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. L OAEL = lowest observed adverse effect le vel. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = 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 num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its most recent registration de cision for metsulfuron-methyl, EPA reviewed these data and select ed the most sensitive endpoints for relevant risk assessmentMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 13 of 55 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 whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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 pest icide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP scr eening was published on June 14, 2013 1 

### 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, pleas e visit our website. 2



### 5.0 Dietary Exposure and Risk Assessment

5.1 Food Residue Profile

The existing residue chemistry database for mets ulfuron-methyl is adequate for risk assessment purposes. No additional residue ch emistry data are required at th is time. The nature of the residues in plants and animals is adequately understood. Adequate analytical methods (highperformance liquid chromatography/ultraviolet de tection [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-gl ycopyranosyl)benzoate (Metabolite A) and methyl 2-[[[[(4-methoxy-6-methyl-1,3,5-tr iazin-2-yl)amino]carbonyl]amino]sulfonyl]-4- hydroxybenzoate (Metabolite A1) (Memo, B. Cutc hin, 12/17/01; D279786). Metabolite A1 is formed from Metabolite A through enzymatic hydr olysis. 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/Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 14 of 55 Metsulfuron-methyl is the principal degradate in water of the active ingredient iodosulfuronmethyl-sodium (PC Code 122021). As a result, mets ulfuron-methyl is a residue of concern in drinking water following applica tion of iodosulfuron-methyl-sodium . Metsulfuron-methyl is not a residue of concern for risk assessment and to lerance 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 ri sks of the general U.S. population or any population subgroup due to food and drinki ng exposures to metsulfuron-methyl.

5.2 Water Residue Profile

Screening ground water-sourced drinking water e xposure 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 th an produce chemical-specific estimated EDWCs following the usual assessment procedures, EFED provided coarse-screen estimates that should exceed upper-bound chemical-specific EDWCs for a ny 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 pe rsistence 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 Tabl e 5.2.1 (G. Orrick, D427429, 8/12/15).

The chronic dietary assessment for metsulfuron-methyl used th e 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 doe s not underestimate the dietary risks of the general U.S. population or any population subg roup due to food and drinking exposures to metsulfuron-methyl.

Table 5.2.1. PRZM-GW Coarse-Screen EDWCs for Sulfonylureas 1

.

Modeled Scenario K d or K OC Initial ApplicationDates (days postemergence) Max. Dail y Conc. (μg/L) Mean Breakthrough

Time (yrs) Postbreakthrough Mean (μg/L)

WI corn K d 7 449 11.5 415

K OC 7 504 6.9 425

DMV corn K d 7 489 5.3 369

K OC 7 560 3.3 378

FL citrus K d 7 429 3.2 351

K OC 7 467 2.3 349

FL potato K d 7 375 2.6 272

K OC 7 407 2.2 275

GA peanut K d 7 197 5.2 156

K OC 7 206 3.9 158

NC cotton K d 7 640 8.7 492

K d 37 641 8.7 491Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 15 of 55 Table 5.2.1. PRZM-GW Coarse-Screen EDWCs for Sulfonylureas 1

.

Modeled Scenario K d or K OC Initial ApplicationDates (days postemergence) Max. Dail y Conc. (μg/L) Mean Breakthrough

Time (yrs) Postbreakthrough Mean (μg/L)

K d 67 637 8.7 490

K OC 7 742 5.7 484

K OC 37 751 5.7 483

K OC 67 744 5.7 482

1 Maximum values are bolded.



### 5.3 Dietary Exposure and Risk Estimates

HED has conducted a screening-level chronic diet ary risk assessment for metsulfuron-methyl using tolerance-level residues in foods and the sulfonylurea-class-wide sc reening-level estimate of residues in drinking water (G. Orrick, D427429, 8/12/15). Exposure and risk estimates were obtained from the Dietary E xposure Evaluation Model using the Food Commodity Intake Database (DEEM-FCID; version 3.16). The mode l uses food consumption data from the 2003- 2008 National Health and Nutrition Examin ation Survey/What We Eat in America (NHANES/WWEIA) database, couple d with recipe files and re sidues in foods, to derive estimates of dietary exposure and risk.

Generally, HED is concerned wh en chronic dietary exposure estimates exceed 100% of the chronic population adjusted dos e (cPAD). Chronic dietary ri sk estimates (food and drinking water) are not of concern for the general U.S. population or any ot her population subgroup (Table 5.3). The chronic exposure estimate ut ilized 4.4% of the cPAD for the general U.S. population and 11% of the cPAD for all infant s (<1 year old), the most highly-exposed population subgroup. Because of the very conser vative assumptions used in the analysis (tolerance-level residues, 100% crop treated, upper-bound modele d drinking water estimates), actual exposure and risk are expe cted 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 cl assified 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 Drinki ng Water) and Risk for Metsulfuronmethyl 1

.

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 4.3Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 16 of 55 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 residen tial uses that have been assessed in this document to reflect updates to HED’s 2012 Residential SOPs along with polic y changes for body weight assumptions. Therefore, a quantitative assessment of reside ntial 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 anticipat ed from occupational handler exposure for tree injection. It is not anticipated that as many trees would be treate d 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 Es timates for Metsulfuron-methyl.

Exposure Scenario Dermal Unit Exposure (mg/lb ai) Inhalation Unit Exposure (mg/lb ai) Maximum Application Rate 1 Area Treated or Amount Handled Daily 2 Dermal (LOC = 100) Inhalation (LOC = 100)

Dose (mg/kg/day) 3 MOE 4 Dose (mg/kg/day) 5 MOE 6

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/ft 2 1200 ft 2 0.005 25,000 0.00000054 63,000,000
Spoon 6.2 0.087

100 ft 2 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 LiquidsManuallypressurized 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/ft 2 1000 ft 2 0.00015 810,000 0.00000025 130,000,000
Mixer/Loader/Applicator for Dry FlowablesManuallypressurized handwand 69 1.1 0.0004 lb ai/gallon 5 gall ons 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/ft 2 1000 ft 2 0.00015 810,000 0.00000025 130,000,000
1. Based on registered la bels (see table 3.2). 2. Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/scien ce/residential-exposure-sop.html).Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 17 of 55 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) × Applica tion Rate (lb ai/acre or gal) × Area Treated or Amount Handle d (A/day or gallons/day) ÷ Body Weight (80 kg). 6. Inhalation MOE = Inhalation NOAEL (34 mg /kg/day) ÷ Inhalati on Dose (mg/kg/day). 7. Total MOE = NOAEL (mg/kg/day) ÷ (Dermal Dose + Inhalation Dose)


### For post-application scenarios, all adult and child ren 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 granul ar formulations are greater than the LOC (MOEs ≥ 100). Therefore, no risks of concer n were identified for either of these scenarios. A summary of the adult and children short-term derm al 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/cm 2 ) Dermal Dose

2 (mg/kg/day) 2 Dermal MOEs 3
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 Phys ical 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 390,000Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 18 of 55 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/cm 2 ) Dermal Dose

2 (mg/kg/day) 2 Dermal MOEs 3

Child 1 < 2 years old Dermal Phys ical Activites on Turf 0.01 19,000
1. Application rates = maximu m application rates from labels. 2. Dose (mg/kg/day) equati ons provided in Appendix A. 3. Dermal MOE = NOAEL (125 mg/kg/day) / Dermal Dose (mg/kg/day)



### All children oral non-diet ary ingestion risk estimates for bot h 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-diet ary 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 expos ure and risk estimate was not cal culated for children 1 < 2 years old.

Table 6.0.3. Short-Term Oral Non-di etary Ingestion Residential Post-applic ation Exposure and Risk Estimates for Metsulfuron-methyl
Lifestage Post-application Exposure Scenario Application Rate 1 (lb ai/A) TTR (ug/cm 2 ) 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) equa tions provided in Appendix A. 3. Oral MOE = NOAEL (34 mg/kg/day) / Oral Dose (mg/kg/day).



### Turf Transferable Residue (TTR): In accordan ce 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-applic ation exposure to turf. HED de veloped a waiver policy for TTR studies. The MOEs from the assessment, using de fault TTR values, are evaluated. If those are 10 times higher than the level of concern (L OC), 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-me thyl 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 wa iving the 40 CFR TTR data requirement. In this instance, it is unlikely that chemical-specifi c TTR data would be needed to further refine exposure assessments or would add appreciably to our general understandi ng of the availability of turf transferable pesticide residues.

6.1 Spray Drift

A detailed description about HED’ s spray drift policy and how to ev aluate the drift potential and associated risks is available in Appendix G.Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 19 of 55 6.1.1 Combined Risk Estimate s 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 applica tion scenarios. Metsulfuron-methyl is used on a variety of agricultural crops and can be appl ied via groundboom and aerial equipment. The spray drift assessment was conducted using the hi ghest registered applic ation rate of 0.2 lb ai/acre for use on forestry 3 

### . 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 90 th 

### percentile results.

 Aerial applications are based on the use of AgDrift ® 

### Tier 1 aerial opt ion 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 downwi nd direction for entire application/drift event). 4



### Dermal risk estimates have been evaluated for adu lts. 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 incident al oral risk estimates and adult dermal risk estimates from exposure to metsulfuron-methyl relate d to spray drift result in no risks of concern at the field edge for eith er 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 Ex posure 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
Forestry 1
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 forest ry uses because in some situations pesti cides like metsulfuron-methyl are applied in rugged terrain using rotary ai rcraft and smaller droplets. A more appropriate modeling approa ch is currently under development for such situations. Even so, this would not a lter the risk conclusions for the current human health risk ass essment spray drift scenario because, in the cas e of metsulfuron-methyl, if the 100% of application rate assumption is used rather than the screeni ng 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 ai rcraft and smaller droplets. A more appropriate modeling approach is currently under de velopment 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.Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 20 of 55 Table 6.1.2. Children (1 < 2 years old) Risk Esti mates (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

TTR t (ug/cm2) At Edge At Edge

Dermal

MOE Incidental Oral MOE Forestry 1

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 forest ry uses because in some situations pesti cides like metsulfuron-methyl are applied in rugged terrain using rotary ai rcraft and smaller droplets. A more appropriate modeling approa ch is currently under development for such situations. Even so, this would not a lter the risk conclusions for the current human health risk ass essment spray drift scenario because, in the cas e of metsulfuron-methyl, if the 100% of application rate assumption is used rather than the screeni ng level assumptions, there would be no risks of concern.



### 6.2 Residential Bystander Post-Application Inhalation Exposure

Volatilization of pes ticides may be a source of post-ap plication inhala tion exposure to individuals nearby pesticide app lications. The agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insec ticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (S AP) 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 de veloped a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docke tDetail;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 fo r 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 us e in the adult short-term aggregate assessment reflects inhalation exposure from turf applications from manually-pressurized handwand.

 The recommended residential exposure for use inthe children 1 to <2 years old shortterm aggregate assessment reflects hand- to-mouth exposures from post-application exposure to turf applicati ons of liquid formulations.Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 21 of 55 Table 6.3.1. Recommendation for the Residential Exposures for the Metsulfuron-methyl Aggregate Assessment

Lifestage Exposure Scenario Dose (mg/kg/day) 1 MOE 2

Inhalation Oral Total Inhalation Oral Total

Adults Turf Applications FromManuallyPressurized 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/Incident al Oral MOE), where applicable.



### 7.0 Aggregate Exposure and Risk Assessment

HED did not conduct an acute aggr egate dietary exposure/risk asse ssment due to the lack of an endpoint appropriate for acute dietary assessment. A cancer aggregate risk assessment was not performed because metsulfuron-met hyl is classified by HED as “not likely to be carcinogenic to humans.”

There is potential short- and in termediate-term exposure to mets ulfuron-methyl via the dietary and the residential pathways. Since the dermal endpoint was selected fr om a route-specific study and the toxicological effects seen by the dermal r oute 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 co mbined for the aggregate exposure assessment. For adults, the short- and intermediate-term aggr egate 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 we re used to determine the aggregate risk estimate. As noted in Secti on 6.0, there are no dermal risks associated with the existing uses of metsulfuron-methyl. All ag gregate (oral and inhalation) MOEs are greater than 100; therefore, aggregate expo sure 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

Risk 1 Dietary
exposure (food + drinking water) 2 Residential Exposure 3
Total Exposure Aggregate MOE (food and residential) 4 Inhalation Incidental OralMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 22 of 55 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 inte r- and intra- species uncertainty factors, each at 10X). 2 Dietary exposure (mg/kg/day) = chr onic dietary exposure from Table 5.3. 3 Residential exposure (inc idental oral and inhalation exposure) ba sed on recommendations from Table 6.3.1. 4 Aggregate MOE = POD (34 mg/kg/day) ÷ Combin ed dose (dietary + residential, mg/kg/day).



### 8.0 Cumulative Exposure/ Risk Characterization

In 2015, EPA’s Office of Pesticide Programs rele ased a guidance document entitled, Pesticide Cumulative Risk Assessment: Fram ework 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, follo wed 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 chem ical 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 patter n (summarized in Table 3.2.), th ere is a potential for exposure to metsulfuron-methyl in occupational settin gs 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, includi ng types of equipment and techni ques 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 shor t-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 register ed labels require handlers to wear baseline attire and ch emical resistant gloves.

Occupational Handler Exposur e Data and Assumptions

5 Guidance For Identifying Pesticide Chemicals and Other S ubstances 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 us es is listed in Table 3.2.

Unit Exposures: It is the policy of HED to use the best av ailable 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 pred icting handler exposure that are used in this assessment, known as “unit exposures”, are outlin ed in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 7 

### ” 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 website 8



### .
Area Treated or Amount Handled: The area treated or amo unt 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 scenari o. Use information specific to this chemical was not available for this scen ario; therefore, HED used avai lable 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. N o. 352-766) specifies 1 ml per injection site (or 0.00000784 lb ai/injection site) for tr ees as the maximum applicati on rate. Based on assumptions used in the dinotefuran tree inj ection assessment, it is assumed th at one applicator can make 600 trunk injections per day. This assessment assumes then th at the maximum amount of product handled would be 0.0047 lb ai/day (0.00000784 lb ai /injection hole x 600 in jection 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 regist ered uses for metsulfuron-methyl.

9.2 Occupational Post-Application Dermal Exposure/Risk Estimates

Occupational post-application expo sure 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.htmlMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 24 of 55 (DFR) data are required for all occupational (e.g., crop, nursery, gree nhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post-applic ation exposure to foliage. HED developed a waiver policy for DFR studies. The MOEs from the assessment, usi ng 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 scenario s associated with the highest uses for metsulfuron-methyl are summarized in Ta ble C.2 in Appendix C. All scenarios resulted in MOEs greater than the LOC of 100 (ra nging from 410 to 51,000) on day 0 (12 hours after application); and, therefore, are not of concer n to HED. Table C.2. provides the worst-case scenarios for the registered uses for metsulfuron-methyl.

Since the highest estimated occ upational post-applicati on exposure using default DFR values for metsulfuron-methyl is minimal in comparison to th e 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 furthe r refine exposure assessments or would add appreciably to our overall unders tanding of the availability of dislodgeable foliar pesticide residues for metsulfuron-methyl.

Since the estimated occupationa l 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 hi gher 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 understandi ng of the availability of turf transferrable residues for metsulfuron-methyl.

9.3 Occupational Post-Application I nhalation Exposure/Risk Estimates

There are multiple potential sources of post-app lication inhalation exposure to individuals performing post-applicati on activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulat es that contain pesticides. The agency sought expert advice an d input on issues relate d to volatilization of pesticides from its Federal Insecticide, Fungicide , and Rodenticide Act Scie ntific Advisory Panel (SAP) in December 2009, and received th e SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SA P/meetings/2009/120109meeting.html). The agency has evaluated the SAP report and has developed a Vo latilization Screening Tool and a subsequent Volatilization Screening Anal ysis (http://www.regulations .gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the agen cy 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 eval uate the available post- application inhalation exposure data generated by the Ag ricultural Reentry Task Force. Given these two efforts, theMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 25 of 55 Agency will continue to identify the need for and, subsequently, the way to incorporate occupational post-application inhalation expos ure into the agency's risk assessments.

Although a quantitative occupational post-applic ation inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resultin g from application of pesticides outdoors is likely to result in higher exposure than post -application exposure. Therefore, it is expect ed that these handler inhalation exposure estimates would be protec tive of most occupatio nal post-application inhalation exposure scenarios.

Restricted Entry Interval

Metsulfuron-methyl is classified as Toxicity Ca tegory III via the dermal route, Toxicity Category IV for skin irritation potential, a nd Toxicity Category I for primary ey e irritation. It is not a skin sensitizer. Upon review of the criteria for the active ingredientonly, it appears that metsulfuronmethyl is consistent with the criteria in PRN 95-3 that allow fo r a 4-hour REI. Note: The PR Notice also includes similar criteria for the en d-use product. These criteria have not been evaluated by HED. Based solely on the activ e 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 Center s for Disease Control and Prevention/National Institute for Occupational Safety and Health (C DC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) database s 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) invol ving metsulfuron-methyl. Upon re view of these incidents, it was concluded that “Based on the low frequency and severity of incide nt 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 Agri cultural 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 con cern 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 ReferencesMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 26 of 55 Author Barcode Date Title C. Smith, S. Piper, M. Hawkins, S. Dapson D389257 8/30/2011 Metsulfuron-methyl: Re gistration 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) M eetings 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 Requi rements and Toxicology Profile

Table A.1. Metsulfuron-methyl Data Requirements

Test Technical Required Satisfied

870.1100 Acute Oral Toxicity ...................................................... 870.1200 Acute Derm al Toxicity ................................................. 870.1300 Acute Inhala tion Toxic ity ............................................. 870.2400 Primary Ey e Irrita tion ................................................... 870.2500 Primary Derm al Irrita tion ............................................. 870.2600 Dermal Sensitiza tion ..................................................... 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

--- Waived 1 870.3700 Developmental Toxicity (rodent) .................................. 870.3700 Developmental To xicity (nonrodent) ............................ 870.3800 Repr oduction ................................................................ yes yes yes yes yes yes 870.4100a Chronic To xicity (rodent) ............................................. 870.4100b Chronic Toxic ity (nonro dent) ....................................... 870.4200a Carcinog enicity (ra t) ..................................................... 870.4200b Carcinogen icity (mouse) ............................................... 870.4300 Chronic Toxicity/Carcinogenicity (rodent) ................... yes yes yes yes yes yes yes yes yes yes 870.5100 Mutagenicity—Gene Mutation - b acterial .................... 870.5300 Mutagenicity—Gen e Mutation - mammalian ............... yes yes yes yesMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 27 of 55 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 Neur otoxicity (hen) .......................................... 870.6200a Acute Neurotox. Sc reening Battery (rat) ...................... 870.6200b 90-Day Neur otoxicity Screening Battery (rat) .............. 870.6300 Developmenta l Neurotoxicity ....................................... no

no yes yes

no ---

--- Waived 1
Waived 1

--- 870.7485 General Metabolis m...................................................... 870.7600 Dermal Penetra tion ....................................................... 870.7800 Immunotoxicity ............................................................ yes

no
yes yes

--- Waived 1

1 Data requirement waived by HASPOC for the 90-day inhalation, acute/subchronic neurotoxici ty, and immunotoxicity studies (TXR#0055652 and TXR#0056723).Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 28 of 55 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 LD 50 > 3000 mg/kg (HDT) III

870.1200 Acute dermal - rabbit
92.9% a.i. 00125828 LD 50 > 2000 mg/kg (ODT) III

870.1300 Acute inhalation - rat
92.9% a.i. 00125830 LC 50 > 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 determinedMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 29 of 55 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 carcinog enic 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 carcinog enic 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



### Page 30 of 55 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 treat ment 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 pare nt 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 co mpound and the four metabolites (saccharin, Metabolites I, II, and III) were found in both matrices.Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 31 of 55 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 receiv ed that review, and are complia nt 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/scien ce/post-app-exposure-data.html.Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 32 of 55 Appendix C. Occupational Short-term/Int ermediate-term Handler Exposure and Risk Estimates for Metsulfuron-methyl.

Table C.1. Occupational Shor t-term/Intermediate-term Handler Exposure and Risk Estimates for Metsulfuron-methyl.

Exposure Scenario Crop or Target 1 Baseline Dermal

Unit Exposure

2 ( μ g/lb ai) Baseline Inhalation Unit Exposure 2 ( μ g/lb ai) Max. Appl. Rate 3 Area Treated

or Amount Handled Daily 4 Baseline Dermal Baseline Inhalation

Dose 5 (mg/kg/day) MOE 6 (LOC =

100) Dose 5 (mg/kg/day) MOE 6 (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 890,000Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 33 of 55 Table C.1. Occupational Shor t-term/Intermediate-term Handler Exposure and Risk Estimates for Metsulfuron-methyl.

Exposure Scenario Crop or Target 1 Baseline Dermal

Unit Exposure

2 ( μ g/lb ai) Baseline Inhalation Unit Exposure 2 ( μ g/lb ai) Max. Appl. Rate 3 Area Treated

or Amount Handled Daily 4 Baseline Dermal Baseline Inhalation

Dose 5 (mg/kg/day) MOE 6 (LOC =

100) Dose 5 (mg/kg/day) MOE 6 (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 320,000Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 34 of 55 Table C.1. Occupational Shor t-term/Intermediate-term Handler Exposure and Risk Estimates for Metsulfuron-methyl.

Exposure Scenario Crop or Target 1 Baseline Dermal

Unit Exposure

2 ( μ g/lb ai) Baseline Inhalation Unit Exposure 2 ( μ g/lb ai) Max. Appl. Rate 3 Area Treated

or Amount Handled Daily 4 Baseline Dermal Baseline Inhalation

Dose 5 (mg/kg/day) MOE 6 (LOC =

100) Dose 5 (mg/kg/day) MOE 6 (LOC = 100)

Applying Sprays forMechanicallyPressurized

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

withManuallyPressurized Handwand Christmas Tree Farm 100,000 30 0.002 lb ai/ gallon 40 gallons 0.1 1,300 0.00003 1,100,000Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 35 of 55 Table C.1. Occupational Shor t-term/Intermediate-term Handler Exposure and Risk Estimates for Metsulfuron-methyl.

Exposure Scenario Crop or Target 1 Baseline Dermal

Unit Exposure

2 ( μ g/lb ai) Baseline Inhalation Unit Exposure 2 ( μ g/lb ai) Max. Appl. Rate 3 Area Treated

or Amount Handled Daily 4 Baseline Dermal Baseline Inhalation

Dose 5 (mg/kg/day) MOE 6 (LOC =

100) Dose 5 (mg/kg/day) MOE 6 (LOC = 100)

M/L/A WDG/DF

withManuallyPressurized 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

withMechanicallyPressurized

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

withMechanicallyPressurized

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

withMechanicallyPressurized

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

withMechanicallyPressurized

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 66,000,000Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 36 of 55 Table C.1. Occupational Shor t-term/Intermediate-term Handler Exposure and Risk Estimates for Metsulfuron-methyl.

Exposure Scenario Crop or Target 1 Baseline Dermal

Unit Exposure

2 ( μ g/lb ai) Baseline Inhalation Unit Exposure 2 ( μ g/lb ai) Max. Appl. Rate 3 Area Treated

or Amount Handled Daily 4 Baseline Dermal Baseline Inhalation

Dose 5 (mg/kg/day) MOE 6 (LOC =

100) Dose 5 (mg/kg/day) MOE 6 (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 withMechanicallyPressurized

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 withMechanicallyPressurized

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 withMechanicallyPressurized

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 withMechanicallyPressurized

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 regist ered uses for metsulfuron-methyl are li sted in this table. 2 “Based on the “Occupational Pesticide Handler Unit Exposure Surr ogate 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 ( μ g/lb ai) ) × Conversion Factor (0.001 mg/ μ g) × 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 ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × 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 = I nhalation 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-app lication Non-Cancer Exposure and Risk Estimates for Metsulfuron-methyl.

Crop/Site Activities Transfer Coefficient

(cm 2 /hr) Application Rate (lb ai/A) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3

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 13,000Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 37 of 55 Table C.2. Occupational Post-app lication Non-Cancer Exposure and Risk Estimates for Metsulfuron-methyl.

Crop/Site Activities Transfer Coefficient

(cm 2 /hr) Application Rate (lb ai/A) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3

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/cm 2 ; where F = 0.25 and D = 0.10 per day 2 Daily Dermal Dose = [DFR (μg/cm 2 ) × 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/cm 2 ) × TC × 0.001 mg/μg × 8 hrs/day × dermal

absorption factor (100 %)]  BW (80 kg).Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 38 of 55 Appendix D. Summary of Occupational and Residential Non-cancer Algorithms

Occupational Non-Cancer Handler Algorithms

Potential daily exposures for occupational handler s 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 pr oposed label (lb ai A or lb ai/gal), and A = area treated or amount ha ndled (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 (der mal 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), whic h is a ratio of the to xicological endpoint to the daily dose of concern. The daily dermal and inhalation dose received by occupational handlers are compared to the a ppropriate POD (i.e., NOAEL) to a ssess 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 HE D 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 Po st-application AlgorithmsMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 39 of 55 Potential daily exposures for occupational post- application workers are calculated using the following formulas:

DFR t 

### =AR * F* (1-D) t 

### * ቀ 4.54E8 ug lb ቁ * ൬ 2.47E-8 A

cm 2 

### ൰

where:

DFR t 

### = dislodgeable foliage residue on day "t" (μg/cm 2 

### ), AR = application rate (lb ai/acre), F = fraction of ai retained on foliage or 25% (unitless), D = fraction of residue that dissipa tes daily or 10% (unitless), and t = number of days afte r application day (days).

E=TC * DFR t 

### * ET * 0.001 mg
ug

where: E = exposure (mg ai/day), TC = transfer coefficient (cm 2 

### /hr), DFR t 

### = dislodgeable foliar re sidue on day “t” (μg/cm 2 

### ), 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 (der mal and/or inhalation), and BW = body weight (kg).

Margin of Exposure: Non-cancer risk estimates for each sc enario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxico logical endpoint to the daily dose of concern. The daily dermal dose received by occupational po st-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



### Page 40 of 55 MOE = margin of exposure: value used by HE D 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) fo r 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, usi ng the equation below:

E = UE * AR * A

where:

E = exposure (mg/day); UE = unit exposure (mg/lb ai); AR = application ra te (e.g., lb ai/ft 2 

### , lb ai/gal); and A = area treated or am ount handled (e.g., ft 2 

### /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 (derma l and/or inhalation); and BW = body weight (kg).

Residential Non-Cancer Po st-Application Algorithms

Post-application Dermal Exposure Algor ithm – Physical Activities on Turf Exposure resulting from contacting previously treat ed turf while performi ng 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 appli cation, it must include “day 0” exposure.

E = TTRt * CF1 * TC * ET

where:

E = exposure (mg/day); TTRt = turf transferable residue on day t ( μ g/cm 2 

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



### Page 41 of 55 TC = transfer coefficient (cm 2 

### /hr); and ET = exposure time (hr/day).

If chemical-specific TTR data are available, th en surface residues from the day of application should be used (assume that individuals coul d be exposed to residues immediately after application). However, if data are not available, then TTR t 

### can be calculated using the following formula:

TTR t 

### = AR * F * (1-FD) t 

### * CF2 * CF3

where:

TTRt = turf transferable residue on day t ( μ g/cm 2 

### ); AR = application rate (lbs ai/ft 2 

### or lb ai/acre); F = fraction of ai as transferable re sidue following app lication (unitless); FD = fraction of residue that dissipates daily (unitless); t = post-application day on whic h exposure is being assessed; CF2 = weight unit conversion factor (4.54 x 10 8 

### μ g/lb); and CF3 = area unit convers ion factor (1.08 x 10 -3 

### ft 2 

### / cm 2 

### or 2.47 x 10 -8 

### acre/cm 2 

### ).

Dermal absorbed doses are calculated as:

BW AF E 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 Activi ties) -- 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

F D Daily residue dissipation (if chemical-specific data is unavailable) (fraction) L/WP/WDG 0.1

Granules 0.1

TC Transfer Coefficient (cm 2 /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 1.5Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 42 of 55 Table D-1: Turf (Physical Activi ties) -- 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 * (F M



### * SA H 

### ) * (ET * N_Replen) * (1- (1- SE) (Freq_HtM/N-Replen) 

### )]

where:

E = exposure (mg/day); HR = hand residue loading (mg/cm 2 

### ); FM = fraction hand surface area mout hed / event (fraction/event); SAH = typical surface area of one hand (cm 2 

### ); 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 cont acts events per hour (events/hour).

and



### 2 * SA DE * Fai HR

H hands 

### 

where:

HR = hand residue loading (mg/cm 2 

### ); Fai hands 

### = fraction ai on hands compared to total su rface residue from dermal transfer coefficient study (unitless); DE = dermal exposure (mg); and SA H 

### = typical surface area of one hand (cm 2 

### ).

Dose, normalized to body we ight, 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



### Page 43 of 55 Table D-2: Turf (Physical Activiti es) – Inputs for Residential Post-application Hand-to-Mouth Exposure Algorithm Notation Exposure Factor (units) Point Estimate(s)

Fai hands Fraction of ai on hands from dermal transfer coefficient study (unitless) Liquid formulations 0.06

Granular formulations 0.027

DE Dermal exposure (mg) Calculated

SA H Typical surface area of one hand (cm 2 ), 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/cm 2 ) Calculated via (DE * Fai hands )/SA H

F M 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 calculate d as follows (based on the algorithm utilized in SHEDS-Multimedia):

E = [OR* CF1 * SAM O 

### * (ET * N_Replen) * (1- (1- SE O 

### ) (Freq_OtM/N_Replen) 

### )]

where:

E = exposure (mg/day); OR = chemical residue loadi ng on the object on day “t” (ug/cm 2 

### ); CF1 = weight unit conver sion factor (0.001 mg/μg); SAM O 

### = area of the object surface that is mouthed (cm 2 

### /event); ET = exposure time (hr/day); N_Replen = number of replenishment intervals per hour (intervals/hour); SE O 

### = 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 * F O 

### * CF2 * CF3

where:

OR = chemical residue loading on the object ( μ g/cm 2 

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



### Page 44 of 55 AR = application rate (lbs ai/ft 2 

### or lb ai/acre); F O 

### = fraction of residue availa ble on the object (unitless); CF2 = weight unit conversion factor (4.54 x 10 8 

### μg/lb); and CF3 = area unit convers ion factor (1.08 x 10 -3 

### ft 2 

### /cm 2 

### or 2.47 x 10 -8 

### acre/cm 2 

### ).

Dose, normalized to body we ight, 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 Re sidential 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.

F O Fraction of AR as OR following application 1 0.01

SAM O Surface area of object mouthed (cm 2 /event) 10
N_Replen Replenishment interv als per hour (intervals/hour) 4

SE O Saliva extraction factor (fraction) 0.48

ET Exposure time (hours per day) 1.5
Freq_OtM Object-to-mouth even ts 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 tr ansferred to the object (e.g., object residue is equal to turf transferable residue).



### Post-application Incidental So il Ingestion Exposure Algorithm– Physical Activities on Turf Exposure from incidental soil inge stion 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-F D 

### ) t 

### * CF2 * CF3 * CF4

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



### Page 45 of 55 SR t 

### = soil residue on day "t" (μg/g); AR = application rate (lbs ai/ft 2 

### or lb ai/acre); FS = fraction of ai available in upp ermost cm of so il (fraction/cm); F D 

### = fraction of residue that dissipates daily (unitless); T = post-application day on whic h exposure is being assessed; CF2 = weight unit conversion factor (4.54 x 10 8 

### μg/lb); CF3 = area unit convers ion factor (1.08 x 10 -3 

### ft 2 

### /cm 2 

### or 2.47 x 10 -8 

### acre/cm 2 

### ); and CF4 = soil volume to weight unit conversion factor (0.67 cm 3 

### /g soil).

Dose, normalized to body we ight, 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-applicatio n 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

F D 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 Ex posure Algorithm– Physical Activities on Turf Exposure from incidental ingesti on 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 we ight, are calculated as:

BW

E D 


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



### Page 46 of 55 E = exposure (mg/day); and BW = body weight (kg).

Table D-5: Turf (Physical Activities ) – Inputs for Residential Post-applic ation Episodic Granular Ingestion Exposure Algorithm Notation Exposure Factor (units) Point Estimate(s)

F D Fraction of active ingredient in dry formulation See table 3.2

AR Application rate (lbs/A or lbs/1,000 ft 2 ) 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 adjust ed if product specific information is available.



### Post-application Dermal Exposure Algorithm – Mowing Exposure resulting from contacting previously tr eated turf while mowing is calculated as follows:

E = TTRt * CF1 * TC * ET

where:

E = exposure (mg/day); TTR t 

### = turf transferable residue on day "t" (μg/cm 2 

### ); CF1 = weight unit conver sion factor (0.001 mg/μg); TC = transfer coefficient (cm 2 

### /hr); and ET = exposure time (hr/day).

and

TTRt = AR * F AR 

### * (1-F D 

### ) t 

### * CF2 * CF3

where:

TTR t 

### = turf transferable residue on day "t" (μg/cm 2 

### ); AR = application rate (lbs ai/ft 2 

### or lb ai/acre); F AR 

### = fraction of ai retain ed on turf (unitless); F D 

### = fraction of residue that dissipates daily (unitless); t = post-application day on whic h exposure is being assessed; CF2= weight unit conve rsion factor (4.54 x 10 8 

### μg/lb); and CF3 = area unit convers ion factor (1.08 x 10 -3 

### ft 2 

### /cm 2 

### or 2.47 x 10 -8 

### acre/cm 2 

### ).

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

BW AF E D *

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



### Page 47 of 55 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 Resi dential 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 AR Fraction of AR as TTR following application L/WP/WDG 0.01

Granules 0.002

F D Daily residue dissipation L/WP/WDG 0.1

Granules 0.1

TC Transfer Coefficient (cm 2 /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 powd er/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); TTR t 

### = turf transferable residue on day "t" (μg/cm 2 

### ); CF1 = weight unit conver sion factor (0.001 mg/μg); TC = transfer coefficient (cm 2 

### /hr); and ET = exposure time (hr/day).

and

TTRt = AR * F * (1-F D 

### ) t 

### * CF2 * CF3

where:

TTR t 

### = turf transferable residue on day "t" (μg/cm 2 

### ); AR = application rate (lbs ai/ft 2 

### or lb ai/acre); F = fraction of ai retained on turf (unitless);’Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 48 of 55 F D 

### = fraction of residue that dissipates daily (unitless); t = post-application day on whic h exposure is being assessed; CF2 = weight unit conversion factor (4.54 x 10 8 

### μg/lb); and CF3 = area unit convers ion factor (1.08 x 10 -3 

### ft 2 

### /cm 2 

### or 2.47 x 10 -8 

### acre/cm 2 

### ).

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

BW AF E 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 Re sidential 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

F D Daily residue dissipation L/WP/WDG 0.1
Granules 0.1 TC Transfer Coefficient (cm 2 /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 powd er/water dispersible granuleMetsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 49 of 55 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 1.000Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 50 of 55 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%**

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



### Page 51 of 55 Appendix F. Nomenclature and Physical/Chemical Properties

Table 1. Metsulfuron-methyl Nomenclature.

Compound Chemical Structure

S N H N H

O O

O O CH 3

N

N CH 3

O CH 3 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 C 14 H 15 N 5 O 6 S

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



### Page 52 of 55 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 Poultry 2

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

2 There are no established tolerances for residues of metsul furon-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(K OW ) 0.018Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 53 of 55 Appendix G. Spray Drift Detailed Description

Off-target movement of pesticides can occur vi a 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 cont act. 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). Th e potential risk estimates from these residues can be calculated using drif t modeling coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorp orating spray drift into risk assessment include assessing exposures for children (1 to 2 years old) and adults w ho 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 associ ated risks, an approach based on drift modeling coupled with techniques used to evaluate residential uses of pest icides 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 s cenario, 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 lawn s where the nearest side of the property was directly adjoining the treated field (at field edge) and at va ried 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 i nput values specified in the recently revised (2012) Standard Operating Procedures For Residential Risk Assessment (SOPs)

. A screening approach was developed for situ ations 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 va lues (i.e., the Tier 1 option) we re incorporated into the model and represent each equipment type and use unde r varied conditions. The screening options specifically recommended in this methodology were selected because they are plausible and represent a reasonable upper bound le vel of drift for common applic ation methods in agriculture. In all cases, each scenario is to be evaluated unl ess it is not plausible ba sed on the anticipated use pattern (e.g., herbicides are not t ypically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are not allowed). Section 6.1.1 provides th e screening level drift related risk estimates.

In many cases, risks are of concern when the screen ing 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 screenin g approach represent actual use practice so risk assessors shou ld be aware and characterize these appropriately.Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 54 of 55 management options additional spray drift depositi on fractions were also considered. These drift estimates represent plausible options ba sed on the available pesticide labels.Metsulfuron-methyl Human-Health Risk Assessment DP No. 427414



### Page 55 of 55 Appendix H. Analytical Standards Summary

Analytical reference standards for metsulfuron-me thyl 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 me tsulfuron methyl metabolite (A1; methyl 2- [[[[(4-methoxy-6-methyl-1,3,5-tria zin-2-yl)amino]carbonyl]amino]s ulfonyl]-4-hydroxybenzoate) (email communication between G. Verdin and J. Van Alstine, 5/7/2015 and 5/11/2015). The registrant is required to mainta in reasonable amounts of the refere nce 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 se nt 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 liste d 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 Occupa tional Safety and Health Administration (OSHA) in 29 CFR §1910.1200.