Mesosulfuron-Methyl Human Health Risk Assessment 0427039 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: September 9, 2015 

OFFICE OF 

CHEMICAL SAFETY ANO 

POLLUTION PREVENTION 

SUBJECT: Mesosulfuron-Methyl. Human Health Draft Risk Assessment for Registration 

Review. 

PC Code: 122009 

Decision No.: 503830 

DP Barcode: 0427039 

Registration Nos.: 264 -694, 264-80 I, 264-802, 264-833, 264-

847, 264-1099, 264- l I 03 

Petition No.: NA Regulatory Action: Registration Review 

Ris k Assessment Type: Single Chemical/Aggregate Case No.: 7277 

TXR No.: NA CAS No.: 208465-21-8 

MRIO No.: NA ~O CFR: § 180.597 

FROM: 

THROUGH: 

TO: 

Kristin Rury, Biologist '?-~ Na

Whan

ncy 

g 

D

Ph

odd

ang, 

, Ch

T

e

ox

mist 

icologist 

~ 

Risk Assessment Branch 3 

Health Effects Division (7509P) 

Christine Olinger, Chief ~/"/~ Risk Assessment Branch 3 l71-0 

Health Effects Division (7509P) 

Jolene Trujillo, Chemical Review Manager 

Risk Management and Implementation Branch V 

Pesticide Re-Registration Division (7508P) 

Mesosulfuron-methyl is a systemic herbicide belonging to the pyrimidinylsulfonylurea group of 

herbicides. It inhibits the action of the plant enzyme acetolactatc synthase (ALS)/acetohydroxy 

acid synthase (AHAS). This document evaluates the existing uses of mesosulfuron-methyl as 

part of Registration Review and represents the draft risk assessment (ORA). The Agency is 

reviewing all the sulfonylurea herbicides jointly under Registration Review. 

Page 1 of 25 
Mesosulfuron-Methyl Human Health Risk Assessment 0427039 

Table of Contents 

1.0 Executive Summary ........................................................................................................... 3 

2.0 HED Recommendations .................................................................................................... 3 

2.1 Tolerance Considerations .............................................................................................. 3 

2.2 Data Deficiencies ............................................................................................................ 3 

3.0 Introduction .................................................................................................................... 4 

3.1 Use Profile & Anticipated Exposure Pathways ........................................................... 4 

3.2 Consideration of Environmenta l J ustice ...................................................................... 5 

4.0 Hazard Characterization .................................................................................................. 6 

5.0 Residue Chemistry ............................................................................................................. 9 

6.0 Dietary Risk Assessment ................................................................................................... 9 

6.1 Water Residue Profile .................................................................................................... 9 

6.2 Dietary (Food+ Water) Exposure Assessment .......................................................... 10 

7.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 11 

7.1 Spra)' Drift .................................................................................................................... 11 

7.2 Residential Bystander Post-Application Inhalation Exposure ................................ 11 

8.0 Aggregate Exposure/Risk Characterization .................................................................. 12 

9.0 Cumulative Exposure/Risk Characterization ............................................................... 12 

10.0 Occupational Exposure/Risk Characterization ............................................................ 12 

11.0 Public Health and Pesticide Epidemiology Data ........................................................... 14 

12.0 References ......................................................................................................................... 14 

Appendix A: Toxicity Profile of Mesosulfuron-Methyl.. ......................................................... 15 

Appendix B: Dietary Exposure/Risk Modeling Input and Output ..................................... 19 

Appendix C: Revie\v of Human Research ............................................................................... 20 

Appendix D: Occupational Non-cancer Handler Exposure Estimates and Algorithms ... 21 

Appendix E. Nomenclature and Physical/Chemical Properties ............................................. 22 

Appendix F. International Harmonization .............................................................................. 23 

Appendix G. DF,R Data Waiver Rationale .............................................................................. 25 

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Mesosulfuron-Methyl Human Health Risk Assessment D427039

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1.0 Executive Summary

Mesosulfuron-methyl, methyl 2-[[[[(4,6-dimethoxy-2-

primidinyl)amino]carbonyl]amino]sulfonyl]-4-[[(methylsulfonyl)amino]methyl]benzoate, 

is a systemic herbicide belonging to the pyrimidinylsulfonylurea class of chemicals. It is

currently registered for use on wheat and triticale. Bayer CropScience is the only registrant with 

mesosulfuron-methyl end-use products. Since the last risk assessment (K. O’Rourke, D298764, 

3/04/2004) and scoping document (N. Dodd, D406414, 04/15/2013), there have been no changes 

to the mesosulfuron use, hazard, or residue profiles. However, dietary exposure to 

mesosulfuron-methyl has been reevaluated in order to incorporate updated consumption data and 

drinking water modeling estimates. Non-dietary exposure has also been reevaluated to 

incorporate changes to occupational exposure assessment methodologies (unit exposures) and to 

incorporate a spray drift assessment. There are no risk estimates of concern for the existing uses 

of mesosulfuron-methyl; however there are some data deficiencies that remain outstanding. 

2.0 HED Recommendations

2.1 Tolerance Considerations

Provided the residue chemistry deficiency cited in Section 2.3 is resolved, the existing tolerances 

(40 CFR 180.597) are supported by the available residue chemistry data. 

At this time, there are no Codex maximum residue limits (MRLs), but there are Canadian MRLs. 

On commodities for which both the US and Canada have tolerances/MRLs, the levels are the 

same. Canada does not establish tolerances on livestock feed items, whereas the US does. 

Canada has established tolerances on more livestock items at 0.01 ppm, whereas the US set a 

tolerance of 0.01 ppm only on meat byproducts of cattle, goat, horse, and sheep. Refer to 

Appendix F. 

HED notes that the tolerance expression for mesosulfuron-methyl requires revision to state the 

following:

Tolerances are established for residues of mesosulfuron-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 mesosulfuronmethyl, methyl 2-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-4-

[[(methylsulfonyl)amino]methyl]benzoate.

2.2 Data Deficiencies 

860.1340 Residue Analytical Method

The independent laboratory validation of the livestock enforcement method, Method EM F07/00-

0, is adequate provided that the method is revised to make it confirmatory, preferably by using 

three-ion monitoring or total ion chromatogram full scan. Provided that the method is revised to 

be confirmatory, EPA will not require that an interference study be conducted to show whether 
Mesosulfuron-Methyl Human Health Risk Assessment D427039

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other pesticides registered on the same commodities interfere with determination of 

mesosulfuron-methyl (N. Dodd, D396429, D396433, D396434, 07/30/2013).

3.0 Introduction 

3.1 Use Profile & Anticipated Exposure Pathways 

Mesosulfuron-methyl is only formulated as water-dispersible granule (WG) formulations and 

only registered for use on wheat and triticale. Currently registered labels include one technical 

label, six agricultural labels, and three special local need (SLN) state labels. In general, 

mesosulfuron-methyl may be applied to wheat and triticale only once per year or once per 

growing season. Application timing varies depending on the target weed (before or after 

emergence of the weeds or the crop itself). The registered application rates range from 0.0028 to 

0.013 lb ai/A. Mesosulfuron-methyl may be applied using groundboom and aerial application 

equipment; application via chemigation is not permitted. The mesosulfuron-methyl labels 

require occupational handlers to wear baseline personal protective equipment (PPE): long 

sleeved shirts, long pants, shoes, and socks; chemical resistant gloves; and protective eyewear. 

The restricted entry intervals (REIs) listed on the mesosulfuron-methyl labels are either 4 hours, 

12 hours, or 24 hours. 

Individuals may be exposed to mesosulfuron-methyl via their diet (food and drinking water) and 

agricultural workers may be exposed (dermally and via inhalation) to mesosulfuron-methyl 

during mixing, loading, and/or applying the herbicide as well as during post-application 

activities. There are no registered uses for mesosulfuron-methyl that will result in direct nondietary (i.e., residential) exposures. However, there is the potential for indirect exposure

(incidental oral and dermal) to mesosulfuron-methyl related to spray drift. 

Table 3.1. Summary of Directions for Use of Mesosulfuron-Methyl.

Applic. 

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. 

No.]

Applic. 

Rate (lb 

ai/A)

Max. No. 

Applic. per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)

REI 

(Hours) Use Directions and Limitations

Wheat and Triticale

Aerial and 

Ground 

Equipment*

Water 

dispersible 

granule

[264-801]

0.0028 1 0.0028 24

Apply as a foliar spray in wheat to 

control wild oat and wild mustard. 

Apply to young and actively growing 

weeds. Do not apply within 30 days of 

harvest for forage, 50 days for hay, 55 

days for grain and straw.

Water 

dispersible 

granule

[264-802]

0.013 1 0.013 4**

Apply when wheat from emergence up 

to jointing stage of growth. Do not 

apply within 30 days of harvesting 

wheat forage, and 60 days for hay, 

grain, or straw.

Water 

dispersible 

granule

[264-833]

0.010 1 0.010 24

Apply to post-emergent wheat up to 

jointing. PHI = 30 days for forage, 71 

days for grain and straw.
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Table 3.1. Summary of Directions for Use of Mesosulfuron-Methyl.

Applic. 

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. 

No.]

Applic. 

Rate (lb 

ai/A)

Max. No. 

Applic. per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)

REI 

(Hours) Use Directions and Limitations

Water 

dispersible 

granule

[264-847]

0.0029 1 0.0029 12

Apply from emergence. PHI for forage 

= 30 days, for grain and straw = 71 

days.

Water 

dispersible 

granule

[264-1099]

0.0036 1 0.0036 12

Apply from emergence. PHI for forage 

= 30 days, for grain and straw = 71 

days.

Water 

dispersible 

granule

[264-1103]

0.013 1 0.013 12

Apply up to the jointing stage of 

growth. PHI 30 days for forage, 60 

days for hay, grain, straw.

*Chemigation is not permitted on the registered labels.

**See Section 10.0 for a description of the requirements for reduced REI for EPA Reg. No. 264-802. At this time, the end-use 

product meets the acute toxicity criteria for a reduced REI of 4 hours. 

3.2 Consideration of Environmental Justice

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

preliminary human health risk assessment for mesosulfuron-methyl, in accordance with U.S. 

Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority 

Populations and Low-Income Populations,"

http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf. As a part of every 

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

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

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

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

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

National Health and Nutrition Examination Surveys/What We Eat in America 

(NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a 

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

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

exposure assessments are performed when conditions or circumstances warrant. Whenever

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

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

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

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

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

patterns among specific subgroups. 
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4.0 Hazard Characterization

The toxicology database for mesosulfuron-methyl is complete. The data requirements for a 

dermal toxicity study, acute and subchronic neurotoxicity studies, a subchronic inhalation 

toxicity study, and an immunotoxicity study are waived (TXR: 0056562; 02/21/2013 & TXR: 

0056723, 08/06/2013). The latest risk assessment was conducted in 2004 (K. O’Rourke, 

D298764, 3/04/2004). No new toxicity and/or metabolism data have been received and the 

endpoints selected for the previous risk assessment remain the same. A summary of the acute, 

subchronic, and chronic toxicity profile is presented in Appendix A.

4.1 Summary of Toxicological Effects

With oral administration in rats, absorption was quick (detected in the blood 15 minutes postdose), but the quantity absorbed was low. Based on the radioactivity found in urine, feces, and 

the contents of the stomach and intestines; maximal absorption was approximately 30% of the 

administered dose. The primary route of elimination was via feces. Bioaccumulation was 

negligible as indicated by <0.1% of the administered dose in the tissues examined.

The existing data show that with repeated oral dosing mesosulfuron-methyl produced very low 

toxicity in rats, mice, rabbits, and dogs. Low oral toxicity could be, in part, due to low oral 

absorption (30%). In the 90-day oral toxicity studies in rats, mice, and dogs, no toxicity was 

seen at the highest dose levels tested, ranging from 648 to 1603 mg/kg/day. In developmental 

toxicity studies in rats and rabbits, no maternal or developmental effects were found at the limit 

dose (1000 mg/kg/day). A two generation reproduction study in rats showed no parental, 

reproductive, or offspring effects at the highest dose tested (1387 mg/kg/day), which exceeded 

the limit dose for a reproductive toxicity study. In the one year toxicity study in dogs, increased 

mucus secretion in the cardiac and fundic sections of stomach was seen in male dogs at 574 

mg/kg/day. 

No increase in tumor incidence was seen in rats and mice, which received doses approaching or 

above the limit dose (952 mg/kg/day and 1356 mg/kg/day), respectively; in addition, no systemic 

toxicity was seen at highest tested dose levels for rats and mice in long-term (chronic) studies. 

Mesosulfuron-methyl was not genotoxic. There was no evidence of neurotoxicity in the database.

The acute toxicity data indicate that mesosulfuron-methyl had low acute oral, dermal, and 

inhalation toxicity. It was not found to be a skin irritant, and irritation that occurred in the eye 

was cleared up 48 hours after exposure. Mesosulfuron-methyl was not a dermal sensitizer.

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

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

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

quantitative susceptibility in the young; there is no evidence of neurotoxicity with mesosulfuronmethyl, and exposure estimates are unlikely to underestimate risk; therefore, the FQPA Safety 

Factor (10x) is reduced to 1x.
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4.3 Toxicity Endpoint and Point of Departure Selections

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

Some studies used for endpoint selection have conservative NOAEL/LOAEL values that have 

not been updated to reflect current standards for evaluating toxicity studies. Updates would 

result in higher NOAEL/LOAEL values and, given the current risk picture, would not impact the 

overall findings of the risk assessment. An incidental oral POD was not selected because there 

were no effects seen in any applicable studies (90-day oral toxicity studies, reproductive toxicity 

studies, or developmental toxicity studies) with which to derive an incidental oral POD. 

Table 4.3.1. Summary of Toxicity Endpoints and Points of Departure for Mesosulfuron-methyl for Use in 

Human Risk Assessment.

Exposure

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, Level 

of Concern for 

Risk Assessment

Study and Toxicological Effects

Acute Dietary:

All populations An endpoint attributable to a single dose was not identified in the database.

Chronic Dietary:

All populations

NOAEL= 155

mg/kg/day

UFA = 10

UFH = 10

FQPA SF = 1X

Chronic RfD = 

1.55 mg/kg/day

cPAD = 1.55

mg/kg/day

Chronic oral toxicity study in dogs.

LOAEL = 574 mg/kg/day [M] 

based on increased mucus secretion 

in the cardiac and fundic sections 

of the stomach, and chronic 

superficial gastritis (1/6) of male 

dogs.

Incidental Oral: 

Short- and 

IntermediateTerm)

Quantification of incidental oral risk is not required because there were no effects seen in any 

applicable studies (90-day oral toxicity studies, reproductive toxicity studies, or 

developmental toxicity studies) in order to derive an incidental oral POD. 

Dermal 

Exposure: Short-, 

Intermediate- and 

Long-Term

Quantification of dermal risk is not required for this route of exposure due to the lack of 

dermal, systemic, neurological, and developmental toxicity concerns. 

Inhalation 

Exposure: Short-, 

Intermediate- and 

Long-Term

Oral NOAEL= 

155

mg/kg/day

(Inhalation 

toxicity 

assumed to be 

equivalent to 

oral)

UFA = 10

UFH = 10

FQPA SF = 1X

Residential LOC 

for MOE = NA

Occupational 

LOC for MOE = 

100

Chronic oral toxicity study in dogs.

LOAEL = 574 mg/kg/day [M] 

based on increased mucus secretion 

in the cardiac and fundic sections 

of the stomach, and chronic 

superficial gastritis (1/6) of male 

dogs.

Cancer (oral, 

dermal, 

inhalation)

“Not likely to be carcinogenic to humans” based on the lack of evidence of carcinogenicity in 

the rats and mice. 

UF = uncertainty factor, UFA = extrapolation from animal to human (interspecies), UFH = potential variation in 

sensitivity among members of the human population (intraspecies), NOAEL = no observed adverse effect level, 

LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = 

reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable, FQPA = Food Quality 

Protection Act.
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4.4 Endocrine Disruption

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

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

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

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

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

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

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

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

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

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

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

metsulfuron-methyl is subject to the endocrine screening part of the Endocrine Disruptor 

Screening Program (EDSP). 

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

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

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

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

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

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

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

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

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

pesticides scheduled for Registration Review and chemicals found in water. Neither of these 

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

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

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

website.2

 

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

chemicals.

2 http://www.epa.gov/endo/
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5.0 Residue Chemistry

The nature of the residue in wheat, ruminants, and poultry is adequately understood based on 

metabolism studies in wheat, dairy cows, and poultry. Parent was the major residue in wheat 

forage and hay and in most livestock commodities. The residue of concern for tolerance 

enforcement and dietary risk assessment in wheat and livestock commodities is the parent 

compound only. 

An analytical reference standard for mesosulfuron-methyl with an expiration date of 3/21/2016 is 

available at EPA’s National Pesticide Standards Repository (e-mail dated 5/11/2015 from 

Gregory Verdin, Analytical Chemistry Branch/Biological and Economic Analysis Division). 

The structure and the physical/chemical properties are summarized in Appendix E. 

6.0 Dietary Risk Assessment

An updated dietary exposure assessment has been completed for mesosulfuron-methyl for the 

DRA to incorporate updated food consumption data and drinking water modeling estimates. The 

use pattern, PODs, and residue inputs to the dietary assessment have not changed since the 

previous assessment. 

6.1 Water Residue Profile 

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

Pesticide Root Zone Model for Ground Water (PRZM-GW; v.1.07) for use in the SU dietary risk 

assessments. Rather than produce chemical-specific estimated drinking water concentrations 

(EDWCs) following the usual assessment procedures, the Environmental Fate and Effects 

Division (EFED) provided coarse-screen estimates that should exceed upper-bound chemicalspecific EDWCs for any SU. This was achieved by using model inputs that represent the use 

pattern of highest exposure from any SU, the highest soil mobility of any SU residue of concern, 

and persistence to any route of degradation over time. The resulting highest coarse-screen 

EDWCs from PRZM-GW can be used as conservative estimates of exposure and are 

summarized in Table 6.1 (G. Orrik, D427429, 08/12/2015). 

The chronic dietary assessments for mesosulfuron-methyl used the post-breakthrough time it 

takes the compound to reach the ground water after application) mean value of 492 μg/L (0.492 

ppm). 

Table 6.1. PRZM-GW Coarse-Screen EDWCs for Sulfonylureas1.

Modeled Scenario Kd or KOC

Initial Application 

Dates (days postemergence)

Max. Daily Conc. 

(μg/L)

Mean 

Breakthrough 

Time (yrs)

Postbreakthrough 

Mean (μg/L)

WI corn

Kd 7 449 11.5 415

KOC 7 504 6.9 425

DMV corn

Kd 7 489 5.3 369

KOC 7 560 3.3 378
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Table 6.1. PRZM-GW Coarse-Screen EDWCs for Sulfonylureas1.

Modeled Scenario Kd or KOC

Initial Application 

Dates (days postemergence)

Max. Daily Conc. 

(μg/L)

Mean 

Breakthrough 

Time (yrs)

Postbreakthrough 

Mean (μg/L)

FL citrus

Kd 7 429 3.2 351

KOC 7 467 2.3 349

FL potato

Kd 7 375 2.6 272

KOC 7 407 2.2 275

GA peanut

Kd 7 197 5.2 156

KOC 7 206 3.9 158

NC cotton

Kd 7 640 8.7 492

Kd 37 641 8.7 491

Kd 67 637 8.7 490

KOC 7 742 5.7 484

KOC 37 751 5.7 483

KOC 67 744 5.7 482

1 Maximum values are bolded and were used in the chronic dietary assessment.

6.2 Dietary (Food + Water) Exposure Assessment

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

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

residues in drinking water (G. Orrik, D427429, 08/12/2015). Exposure and risk estimates were 

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

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

2008 NHANES/WWEIA (National Health and Nutrition Examination Survey, What We Eat in 

America) database, coupled with recipe files and residues in foods, to derive estimates of dietary 

exposure and risk. Generally, HED is concerned when dietary exposure estimates exceed 100% 

of the population adjusted dose (PAD). In the case of mesosulfuron-methyl, the dietary risk 

estimates (Table 6.2) range from <1.0 to 1.7% of the cPAD and are below HED’s level of 

concern. Because of the very conservative assumptions used in the analysis (tolerance level 

residues, 100 % crop treated, upper-bound modeled drinking water estimates), actual exposure 

and risk are expected to be much lower than those shown in Table 6.2. The listings of inputs and 

outputs to the assessment are included in Appendix B. HED did not conduct an acute dietary 

exposure/risk assessment because an acute dietary POD was not selected for mesosulfuronmethyl. Mesosulfuron-methyl is considered “not likely to be carcinogenic to humans”; therefore 

a cancer dietary risk assessment was also not conducted. 

Table 6.2. Summary of dietary exposure and risk estimates for Mesosulfuron-methyl.

Population Group

Chronic Estimates

Exposure, mg/kg bw/day Risk, % cPAD

Total US Population 0.010351 <1.0

All Infants (< 1 year old) 0.026592 1.7

Children 1-2 years old 0.014983 1.0

Children 3-5 years old 0.012643 <1.0
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Table 6.2. Summary of dietary exposure and risk estimates for Mesosulfuron-methyl.

Population Group

Chronic Estimates

Exposure, mg/kg bw/day Risk, % cPAD

Children 6-12 years old 0.009120 <1.0

Youth 13-19 years old 0.007565 <1.0

Adults 20-49 years old 0.010317 <1.0

Adults 50-99 years old 0.010193 <1.0

Female 13-49 years old 0.010279 <1.0

7.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no registered residential uses or occupational uses resulting in residential exposure to 

mesosulfuron-methyl. Therefore, a quantitative residential exposure assessment was not 

performed. 

7.1 Spray Drift 

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g. groundboom) employed 

for mesosulfuron-methyl.

An incidental oral POD was not established for mesosulfuron-methyl because there were no 

effects seen in any applicable studies of an appropriate duration to evaluate short-term incidental 

oral exposure resulting from spray drift of mesosulfuron-methyl (90-day oral toxicity studies, 

reproductive toxicity studies, or developmental toxicity studies). A dermal POD was not 

established because there were no dermal or systemic effects seen in the subchronic dermal 

toxicity study; and there was no developmental or reproductive toxicity seen throughout the 

database. Therefore a quantitative spray drift assessment was not conducted for mesosulfuronmethyl. 

7.2 Residential Bystander Post-Application Inhalation Exposure

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

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

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

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

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

subsequent Volatilization Screening Analysis.3 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 mesosulfuron-methyl.

 

3 Available at: http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219.
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8.0 Aggregate Exposure/Risk Characterization

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

chemical residues. Exposures to be aggregated include anticipated dietary, residential handler, 

and residential post-application exposures. Since there are no residential uses for mesosulfuronmethyl that would result in contributions to the aggregate assessment, short- and intermediateterm aggregate risk assessments are not required. Aggregate exposure and risk estimates are 

equivalent to the dietary exposure and risk estimates discussed in Section 6 of this document, and 

are not of concern. 

9.0 Cumulative Exposure/Risk Characterization

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

Cumulative Risk Assessment: Framework for Screening Analysis 

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

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

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

framework supplements the existing guidance documents for establishing common mechanism 

groups (CMGs)[1] and conducting cumulative risk assessments (CRA)[2]. The Agency has 

utilized this framework to evaluate the SUs of which mesosulfuron-methyl is a member (J. 

D’Agostino, D428798, 09/09/15). Although the SUs share some chemical and toxicological 

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

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

evaluation is necessary.

10.0 Occupational Exposure/Risk Characterization

Dermal exposure during handling activities was not considered because systemic toxicity was 

not observed at the limit dose in the dermal study. An occupational handler exposure and risk 

assessment was conducted using an inhalation POD derived from the chronic oral toxicity study 

in dogs. This is considered a conservative assessment because of the exposure duration of the 

selected study for the POD. Only short- and intermediate-term exposures are expected for 

mesosulfuron-methyl; however the POD conservatively represents effects likely only seen after 

intermediate-term or chronic exposure durations. 

The occupational handler inhalation risk estimates indicate that short- and intermediate-term 

non-cancer inhalation MOEs are not of concern to HED (i.e. MOEs > 100) with baseline attire

(no respirator). The lowest MOE of 89,000 represents the most protective worst-case 

occupational scenario: mixing/loading dry flowables (water-dispersible granules) to support 

aerial applications to high acreage crops (i.e. wheat). 

 

[1] Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common Mechanism of Toxicity (USEPA, 

1999)

[2] Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity (USEPA, 

2002)
Mesosulfuron-Methyl Human Health Risk Assessment D427039

Page 13 of 25

Dermal exposure during post-application activities was not considered because no systemic 

toxicity was observed at the limit dose in the dermal study. Based on the Agency's current 

practices, a quantitative occupational post-application inhalation exposure assessment was not 

performed for mesosulfuron-methyl at this time. If new policies or procedures are put into place, 

the Agency may revisit the need for a quantitative occupational post-application inhalation 

exposure assessment for mesosulfuron-methyl. 

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

mesosulfuron-methyl. For additional details, see Appendix G. 

Restricted Entry Interval (REI)

Based on the acute toxicity categories and post-application assessment for mesosulfuron-methyl, 

the Worker Protection Standard (WPS) Interim Restricted Entry Interval (REI) for mesosulfuronmethyl is 12-hours. REIs may be further reduced if certain criteria are met in accordance with 

the Pesticide Registration (PR) Notice 95-3 [Reduction of WPS Interim REIs for Certain Low 

Risk Pesticides]4. In PR Notice 95-3, there are a set of criteria listed for the active ingredient that 

must be met for chemicals to be eligible for a reduced REI. These criteria include:

1. The active ingredient is in Toxicity category III or IV based upon data for acute dermal 

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

Acute oral toxicity data were used if no acute dermal data were available. If EPA lacked 

data on primary skin irritation, acute inhalation, or primary eye irritation of the active 

ingredient, the Agency reviewed data on that end-point for similar active ingredients 

(analogs), and excluded such active ingredients from consideration for the reduced REI, 

if the analog is in Toxicity Category I or II for that endpoint.

2. The active ingredient is not a dermal sensitizer (or in the case of biochemical and 

microbial active ingredients, no known reports of hypersensitivity exist).

3. The active ingredient is not a cholinesterase inhibitor (NMethyl carbamate and 

Organophosphate) as these chemicals are known to cause large numbers of pesticide 

poisonings and have the potential for serious neurological effects.

4. No known reproductive, developmental, carcinogenic, or neurotoxic effects have been 

associated with the active ingredient. If active ingredients did not have data available for 

these chronic health effects, EPA considered data on appropriate chemical and biological 

analogs. Active ingredients that have been classified as carcinogenic in Category B 

(probable human carcinogen) or Category C with a potency factor, Q* (possible human 

carcinogen, for which quantification of potential risk is considered appropriate), or are 

scheduled for the Health Effects Division's Cancer Peer Review process, were omitted 

from consideration.

5. EPA does not possess incident information (illness or injury reports) that are ``definitely'' 

or ``probably'' related to post-application exposures to the active ingredient.

Upon review of the criteria for the active ingredient only, it appears that mesosulfuron-methyl is 

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

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

 

4 Available: http://www.epa.gov/PR_Notices/pr95-3.html
Mesosulfuron-Methyl Human Health Risk Assessment D427039

Page 14 of 25

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

REI for mesosulfuron-methyl.

11.0 Public Health and Pesticide Epidemiology Data

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

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

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

on the active ingredient mesosulfuron-methyl in 2013 and no incidents of concern were 

identified (S. Recore, D409035, 02/07/2013); therefore additional analysis is not required. 

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

this study does not provide any additional information on mesosulfuron-methyl. The Agency 

will continue to monitor the incident information and if a concern is triggered, additional 

analysis will be included in the risk assessment.

12.0 References

Author Barcode Date Title

C. Stafford D298702 3/25/04 PP# 1F06298. Review of Residue Analytical Methods Submitted to 

Support Food Tolerances for Mesosulfuron-methyl. Chemical # 122009.

N. Dodd D396429 7/30/13 Mesosulfuron-methyl. Independent Laboratory Validation and Storage 

Stability Data on Wheat. 

N. Dodd D406414 4/16/13 Mesosulfuron-methyl. Human Health Assessment Scoping Document in 

Support of Registration Review. 

N. Dodd D284051 2/18/04 Mesosulfuron-methyl. Petition for the Establishment of Permanent 

Tolerances on Wheat. Summary of Analytical Chemistry and Residue 

Data. PP#1F06298.

K. O’Rourke D298764 4/4/04 Human Health Risk Assessment for Mesosulfuron-methyl to Support 

Request for New Active Ingredient Uses on Wheat.

S. Mathur D297240 1/15/04 Product Chemistry Review of Mesosulfuron-methyl Technical/MUP

S. Recore D409035 2/7/13 Mesosulfuron-methyl: Review of Human Incidents

J. Van Alstine TXR # 

0056562

2/21/13 Mesosulfuron-Methyl: Summary of Hazard and Science Policy Council 

(HASPOC) Meeting of January 17, 2013: Recommendations on the Need 

for a Subchronic Inhalation Toxicity, a Subchronic Dermal Toxicity, 

Neurotoxicity Battery (Acute and Subchronic), and Immunotoxicity 

Studies. 

K. Rury TXR # 

0056723

8/6/13 Sulfonylureas: Summary of Hazard and Science Policy Council 

(HASPOC) Meeting on July 18, 2013: Recommendations on Data 

Requirement for Immunotoxicity Studies for Sulfonylurea Pesticides.

S. Winfield D298763 3/3/04 Occupational and Residential Risk Assessment to Support Request for a 

Section 3 Registration of Mesosulfuron-methyl on Wheat
Mesosulfuron-Methyl Human Health Risk Assessment D427039

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Appendix A: Toxicity Profile of Mesosulfuron-Methyl 

Table A.1. Mesosulfuron-methyl Toxicity Data Requirements.

Test Technical

Required Satisfied

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

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

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

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

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

870.3200 21/28-Day Dermal ........................................................

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

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

yes

yes

yes

no

yes

yes

yes

waived1

---

waived1

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

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

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

yes

yes

yes

yes

yes

yes

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

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

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

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

yes

yes

yes

yes

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

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

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

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

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

no

no

yes

yes

no

---

---

waived1

waived1

---

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

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

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

yes

no

yes

yes

---

waived2

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

immunotoxicity studies:

1: TXR#0056562 and 2: TXR#0056723.
Mesosulfuron-Methyl Human Health Risk Assessment D427039

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Table A.2. Acute Toxicity of Mesosulfuron-methyl – Technical.

Guideline 

No.

Study Type MRID No. Results Toxicity 

Category

870.1100 Acute oral toxicity-rats 45386321 LD50 > 5000 mg/kg [M/F] IV

870.1200 Acute dermal toxicityrats 45386322 LD50 > 5000 mg/kg [M/F] IV

870.1300 Acute inhalation 

toxicity-rats 45386323 LC50 > 1.33 mg/kg [M/F] III

870.2400 Acute eye irritation -

rabbits 45386324 Conjunctival irritation at 24 hrs in 1/3 of 

test animals. Cleared by 48 hrs. III

870.2500 Acute dermal irritationrabbits 45386325 Non Irritant IV

870.2600 Skin sensitizationguinea pigs 45386326 Unacceptable Negative 1

1 There was no indication that the material is a dermal sensitizer; however, the study is unacceptable because the submitted positive control 

 study was not conducted within 6 months (i.e., they were approximately 9 months apart).

Table. A.3. Subchronic, Chronic and Other Toxicity of Mesosulfuron-methyl Technical

Guideline No./ 

Study Type

MRID No. (year)/ Classification 

/Doses Results

870.3100

90-Day oral toxicity 

in rats

45386327 (1999)

Acceptable/guideline

0, 240, 1200, 6000, 12000 ppm

M: 0, 17.5, 88.6, 435, 908 mg/kg/day

F: 0,19.1, 96.1, 475, 977 mg/kg/day

NOAEL = 908/977 [M/F] mg/kg/day

LOAEL = not observed.

870.3100

90-Day oral toxicity 

in mice

45386328 (1999)

Acceptable/guideline

0, 140, 1000, 7000 ppm

M: 0, 25.5, 176.1, 1238.3 mg/kg/day

F:0, 32.3, 206.1, 1603.4 mg/kg/day

NOAEL = 1238.3/ 1603.4 [M/F] mg/kg/day

LOAEL = not observed.

870.3150

90-Day oral toxicity 

in dogs

45386329 (2000)

Acceptable/guideline

0, 750, 3750, 7500 ppm

M: 0, 63, 348, 648 mg/kg/day

F:0, 75, 348, 734 mg/kg/day

NOAEL = 648/ 734 [M/F] mg/kg/day

LOAEL = not observed.

70.3200

21/28-Day dermal 

toxicity

Waived (TXR: 0056562; 2/21/2013).

870.3465

90-Day inhalation 

toxicity

Waived (TXR: 0056562; 2/21/2013).

870.3700a

Prenatal 

developmental in 

rats

45430404 (1999)

Acceptable/guideline

0, 100, 315, 1000 mg/kg/day

Maternal NOAEL = 1000 mg/kg/day

LOAEL = not observed

Developmental NOAEL = 1000 mg/kg/day

LOAEL = not observed

870.3700b

Prenatal 

developmental in 

rabbits

45386401 (1998)

Acceptable/guideline

0, 100, 315, 1000 mg/kg/day

Maternal NOAEL = 1000 mg/kg/day

LOAEL = not observed

Developmental NOAEL = 1000 mg/kg/day

LOAEL = not observed

870.3800 45430405 (2000)

Acceptable/guideline

Parental/Systemic NOAEL = 1175.2/ 1387.6 

[M/F] mg/kg/day
Mesosulfuron-Methyl Human Health Risk Assessment D427039

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Table. A.3. Subchronic, Chronic and Other Toxicity of Mesosulfuron-methyl Technical

Guideline No./ 

Study Type

MRID No. (year)/ Classification 

/Doses Results

Reproduction and 

fertility effects in 

rats

0,160, 1600, 16000 ppm

M: 0, 11.7, 115.3, 1175.2 mg/kg/day

F: 0, 13.5, 132.6, 1387.6 mg/kg/day

LOAEL = not observed

Reproductive NOAEL = 1175.2/ 1387.6 [M/F] 

mg/kg/day

LOAEL = not observed

Offspring NOAEL = 1175.2/ 1387.6 [M/F] 

mg/kg/day

LOAEL = not observed

870.4100a

Chronic toxicity in 

rats

45430402 (2000)

Acceptable/guideline

0, 160, 1600, 16000 ppm

M: 0, 7.46, 73.8, 764 mg/kg/day

F: 0, 9.39, 94.7, 952 mg/kg/day

NOAEL = 764/ 952 [M/F] mg/kg/day

LOAEL = not observed.

870.4100b

Chronic toxicity in 

dogs

45386330 (2000)

Acceptable/guideline

0, 400, 4000, 16000 ppm

M: 0, 14.7, 155, 574, mg/kg/day

F: 0, 15.3, 169, 646 mg/kg/day

NOAEL = 155 [M] mg/kg/day

LOAEL = 574 [M] mg/kg/day based on increased 

mucus secretion in the cardiac and fundic sections 

of the stomach of the males dogs (HDT) and 

chronic superficial gastritis (1/6).

870.4200

Carcinogenicity rats

45430402 (2000)

Acceptable/guideline

0, 160, 1600, 16000 ppm

M: 0, 7.46, 73.8, 764 mg/kg/day

F: 0, 9.39, 94.7, 952 mg/kg/day

NOAEL = 764/ 952 [M/F] mg/kg/day

LOAEL = not observed.

No evidence of carcinogenicity

870.4300

Carcinogenicity 

mice

45430403 (2000)

Acceptable/guideline

0, 80, 800, 8000 ppm

M: 0, 10.6, 102.8, 1069.4 mg/kg/day

F: 0, 13.9, 129.8, 1355.6 mg/kg/day

NOAEL = 1069.4/ 1355.6 [M/F] mg/kg/day

LOAEL = not observed.

No evidence of carcinogenicity

Gene Mutation

870.5100

Bacterial reverse 

mutation assay

45386402 (1996)

Acceptable/ guideline

Negative ± S9 up to cytotoxic 5000 μg/ml plate 

Gene Mutation

870.5300

Mammalian cell 

culture

45386404 (1998)

Acceptable/ guideline

Negative ± S9 up to cytotoxic 2500 μg/ml and 

precipitation 250 μg/ml

Cytogenetics 

870.5375 

Chromosomal 

aberrations

45386403 (1998)

Acceptable/ guideline

Negative ± S9 precipitation 100 μg/ml 

Cytogenetics 

870.5395

Micronucleus test 

on mouse

45386406 (1998)

Acceptable/ guideline

Negative at the highest dose tested (limit dose) 

2000 mg/kg (0, 200, 1000, or 2000 mg/kg)

870.5550

Unscheduled DNA

Synthesis

45386405 (1998)

Acceptable/ guideline

(a.i.)

Negative ± S9 precipitation 100 μg/mL 
Mesosulfuron-Methyl Human Health Risk Assessment D427039

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Table. A.3. Subchronic, Chronic and Other Toxicity of Mesosulfuron-methyl Technical

Guideline No./ 

Study Type

MRID No. (year)/ Classification 

/Doses Results

870.6200a

Acute neurotoxicity 

screening battery

Waived (TXR: 0056562; 2/21/2013).

870.6200b

Subchronic 

neurotoxicity 

screening battery

Waived (TXR: 0056562; 2/21/2013).

870.6300

Developmental 

neurotoxicity

Study not required

870.7485

Metabolism and 

pharmacokinetics

45386407- 45386415 (1997- 2000)

Acceptable/guideline

Dose:10 or 1000 mg/kg [phenyl- U14C]- AE F130060

Overall recovery of the radioactive dose was 98-

103%, predominantly recovered in the feces within 

24 hours (80-97% dose). The onset of absorption 

was quick (detected in the blood 15 minutes postdose), but the quantity absorbed was low. Based on 

the radioactivity found in urine, feces, and the 

contents of the stomach and intestines; maximal 

absorption was approximately 30% of the 

administered dose. At 72 hours post-dose (or 168 

hours following the final dose of the repeated 

study), urinary excretion accounted for 1-4% 

(except 13-14% in the 10 mg/kg animals), and 

radioactivity in the bile of the 10 mg/kg animals 

was only 7-9% of the dose by 12 hours post-dose. 

The 10 mg/kg rats had slightly more radioactivity 

in urine and slightly less radioactivity in feces 

compared to the 1000 mg/kg rats. Bioaccumulation 

was not observed, and radioactivity in tissues was 

<0.1% of the dose in all animals at each study 

termination. 

870.7600

Dermal penetration

45386416 (2000)

Unacceptable/ guideline

Doses: 0.0075 cm ai/cm2 or 0.3 mg 

ai/cm2

For both dose groups at each sampling interval, the 

majority of the applied dose was not absorbed 

(73.75-88.10% dose) following a 6-hour exposure 

period. A significant fraction of this material was 

found on the dressings at six hours and was not 

available for absorption.

870.7800

Immunotoxicity 

Waived (TXR: 0056723, 8/6/2013)
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Appendix B: Dietary Exposure/Risk Modeling Input and Output

Filename: C:\Users\ndodd\Documents\DEEM Version 3.16\Mesosulfuron-methyl 041315.r08

Chemical: Mesosulfuron-methyl

RfD(Chronic): 1.55 mg/kg bw/day NOEL(Chronic): 0 mg/kg bw/day

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

Date created/last modified: 04-13-2015/16:14:08 Program ver. 3.16, 03-08-d

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

 EPA Crop Def Res Adj.Factors Comment

 Code Grp Commodity Name (ppm) #1 #2 

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

1500401000 15 Wheat, grain 0.030000 1.000 1.000 

1500401001 15 Wheat, grain-babyfood 0.030000 1.000 1.000 

1500402000 15 Wheat, flour 0.030000 1.000 1.000 

1500402001 15 Wheat, flour-babyfood 0.030000 1.000 1.000 

1500403000 15 Wheat, germ 0.100000 1.000 1.000 

1500404000 15 Wheat, bran 0.030000 1.000 1.000 

3100046000 31 Beef, meat byproducts 0.010000 1.000 1.000 

3100046001 31 Beef, meat byproducts-babyfood 0.010000 1.000 1.000 

3100048000 31 Beef, kidney 0.010000 1.000 1.000 

3100049000 31 Beef, liver 0.010000 1.000 1.000 

3100049001 31 Beef, liver-babyfood 0.010000 1.000 1.000 

3200170000 32 Goat, meat byproducts 0.010000 1.000 1.000 

3200172000 32 Goat, kidney 0.010000 1.000 1.000 

3200173000 32 Goat, liver 0.010000 1.000 1.000 

3500340000 35 Sheep, meat byproducts 0.010000 1.000 1.000 

3500342000 35 Sheep, kidney 0.010000 1.000 1.000 

3500343000 35 Sheep, liver 0.010000 1.000 1.000 

8601000000 86A Water, direct, all sources 0.492000 1.000 1.000 

8602000000 86B Water, indirect, all sources 0.492000 1.000 1.000 
Mesosulfuron-Methyl Human Health Risk Assessment D427039

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Appendix C: Review of Human Research

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

intentionally exposed to a pesticide or other chemical. These data are subject to ethics review 

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

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

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

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.
Mesosulfuron-Methyl Human Health Risk Assessment D427039

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Appendix D: Occupational Non-cancer Handler Exposure Estimates and Algorithms.

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2014); Level of mitigation: Baseline, except for aerial application which is baseline with Eng. 

Controls.

2 Based on registered labels (Reg. No. 264-802 (WDG) and 264-1103 (WDG). These are the labels with the highest application rates for each formulation. 

3 Exposure Science Advisory Council Policy #9.1.

4 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 

kg).

5 Inhalation MOE = Inhalation NOAEL (155 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

Table D. Occupational Handler Non-Cancer Exposure and Risk Estimates for Mesosulfuron-Methyl.

Exposure Scenario Crop or Target Level of Concern

Inhalation Unit 

Exposure (μg/lb ai)1 Maximum

Application Rate2

Area Treated or 

Amount 

Handled Daily3

Inhalation

Baseline (no 

respirator) Dose (mg/kg/day)4 MOE5

Mixer/Loader

Mixing/Loading WDG for Aerial 

Application

Wheat 100 8.96 0.013 lb ai/A

1200 acres 0.00175 89,000

Mixing/Loading WDG for 

Groundboom Application 200 acres 0.000291 530,000

Applicator

Aerial Application

Wheat 100

0.0049

0.013 lb ai/A

1200 acres 0.000000955 160,000,000

Groundboom Application 0.043 200 acres 0.0000111 14,000,000

Flagger

Flagging for Aerial Application Wheat 100 0.35 0.013 lb ai/A 350 acres 0.0000199 7,800,000
Mesosulfuron-Methyl Human Health Risk Assessment D427039

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Appendix E. Nomenclature and Physical/Chemical Properties

Chemical Identity Table

Table E.1. Nomenclature 

Chemical Structure 

Empirical Formula C16H19N5O9S2

Common Name mesosulfuron-methyl

IUPAC Name 2-[(4,6-dimethoxypyrimidin-2-ylcarbamoyl)sulfamoyl]-α-methanesulfonamido-ptoluic acid, methyl ester

CAS Name 2-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-4-

[[(methylsulfonyl)amino]methyl]benzoic acid, methyl ester

CAS Registry Number 208465-21-8

Chemical Class pyrimidinylsulfonylurea herbicide

Table E.2. Physical/Chemical Properties.1

Parameter Value Reference (MRID)

Color cream 45386210

Physical State solid powder 45386211

Odor weakly pungent 45386212

pH 5.1 @ 25C 45386220

Density 1.53 gm/cc at 23C 45386214

Water solubility at 20°C water (pH =5.66)

buffer pH 4

buffer pH 5

buffer pH 7

buffer pH 9

buffer pH 10

2.14 x 10-2 + 0.17 x 10-2

2.15 x 10-3 + 0.14 x 10-3

7.24 x 10-3 + 0.36 x 10-3

0.483 + 0.008

15.39 + 0.32

13.80

Solvent solubility, g/L, at 20C isopropanol 9.6 x 10-2 

acetone 13.66

acetonitrile 8.37

n-hexane <2.29 x 10-4

methylene chloride 3.79

ethyl acetate 2.03

toluene 1.26 x 10-2

45386215
Mesosulfuron-Methyl Human Health Risk Assessment D427039

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Vapor pressure at 20C 3.5 x 10-12 Pascal 45386217

Dissociation constant, pKa, at 

20C

4.35 ± 0.04

45386218

Octanol/water partition 

coefficient

log Po/w = 1.90 (pH 4); 1.39 (pH 5); -0.48 (pH 7); -2.06 

(pH 9); -2.10 (pH 10)

45386219

UV/visible absorption spectrum Not available

1

 D297240, Shyam Mathur, PhD, 1/15/04

Appendix F. International Harmonization

Mesosulfuron-methyl (122009; 4/06/15)

Table 3. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR §180.597(a): Tolerances are established for 

residues of the herbicide mesosulfuron-methyl (methyl 

2-[[[[(4,6-dimethoxy-2-

pyrimidinyl)amino]carbonyl]amino]sulfonyl]-4-

[[(methylsulfonyl)amino]methyl]benzoate])

methyl 2-[[[[(4,6-

dimethoxy-2-

pyrimidinyl)amino]carbon

yl]amino]sulfonyl]-4-

[[(methylsulfonyl)amino]m

ethyl]benzoate

None

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Cattle, meat byproducts 0.01 0.01

Goat, meat byproducts 0.01 0.01

Grain, aspirated fractions 0.60

Horse, meat byproducts 0.01 0.01

Sheep, meat byproducts 0.01 0.01

Wheat, forage 0.60

Wheat, germ 0.10 0.1

Wheat, grain 0.03 0.03

Wheat, hay 0.06

Wheat, straw 0.30

MRLs with No US Equivalent

Eggs 0.01

Fat of cattle 0.01

Fat of goats 0.01

Fat of hogs 0.01

Fat of horses 0.01

Fat of poultry 0.01

Fat of sheep 0.01

Meat byproducts of hogs 0.01

Meat byproducts of poultry 0.01

Meat of cattle 0.01

Meat of goats 0.01

Meat of hogs 0.01

Meat of horses 0.01

Meat of poultry 0.01

Meat of sheep 0.01

Milk 0.01
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Table 3. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Completed by: M. Negussie; 4/10/2015

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Mesosulfuron-Methyl Human Health Risk Assessment D427039

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Appendix G. DFR Data Waiver Rationale

Dislodgeable Foliar Residue (DFR): In accordance with 40CFR158, DFR data are required for 

all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and 

vegetable gardens, pick your own farms, retail tree farms) uses that could result in postapplication exposure to foliage. In the absence of chemical-specific DFR data, EPA uses default 

values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure 

Assessment includes an analysis of a number of DFR studies, which resulted in the selection of a 

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

application (FAR). These values are based on an analysis of 19 DFR studies. Since that time, the 

Agricultural Re-entry Task Force has submitted information (MRID 49299201) that corrects an 

application rate error made in the original submission of “ARF039 – Determination of Dermal 

and Inhalation Exposure to Reentry Workers During Chrysanthemum Pinching in a Greenhouse” 

(EPA MRID 45344501). As a result, the range of FAR values was revised from 2% - 89% to 2% 

- 47%. In the data, a large range of transferability is observed and this variability can potentially 

be attributable to many factors such as active ingredient; formulation; field conditions in the 

studies; weather conditions (e.g., humidity); or many other difficult to quantify factors. 

Although witnessed across multiple chemicals, this range in FAR values is not expected when 

considering DFR data for a single chemical. At this time, the ARTF submission did not alter the 

selection of 25% as the reasonable, high-end default value. 

Since there was no dermal POD selected for mesosulfuron-methyl, an occupational postapplication assessment is not required at this time. Therefore, no additional DFR data are 

required and the 40CFR DFR data requirement is waived.