UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON. D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY A ND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: 15 September 2015 

SUBJECT: Thifensulfuron Methyl. Draft Hwnan Health Risk Assessment in Support of 

Registration Review. 

PC Code: 128845 

Decision No.: 492903 

Petition No.: NA 

DP Barcode: 0 421391 

Registration No.: NA 

Case No.: 7206 

Risk Assessment Type: Single Chemical Aggregate Regulatory Action: Registration Review 

TXR No.: NA CAS No.: 79277-27-3 

MRID No.: None 40 CFR: 180.439 

FROM: Michael A. Doherty, Ph.D., Chemist fo J~ ~~ 

. Z aida Figueroa, DrPH, Industrial ygi,~ni 47 ~ ~ \L--_ 

Karlyn Middleton, M.S., Toxicologist 'L~ Risk Assessment Branch II --··zt-----.__ 

Health Effects Division (7509P) 

THROUGH: Christ

Risk Assess

ina Swartz

ment 

, 

Branch 

Branch 

II 

Chief ~_A­ Health Effects Division (7509P) 

TO: Brittany Pruitt, Chemical Review Manager 

Kelly Sherman, Branch Chief 

Risk Management and Implementation Branch 3 (RMIB 3) 

Pesticide Re-Evaluation Division (7508P) 

As part of registration review, HED has examined the toxicological and exposure databases for 

assessing human health risks associated with thifensulfuron methyl and conducted a new risk 

assessment following current practices and policies. Significant changes relative to the last risk 

assessment (D391088, W. Drew, 2012) include: 

• Establishment of endpoints and points of departure for assessing dermal and incidental 

oral exposure for children; 

• Assessment of spray drift risk for adults and children. 

Page 1 of37 
Table of Contents 

1.0 

2.0 

2.1 

2.2 

3.0 

3.1 

3.2 

3.3 

4.0 

4.1 

4.2 

4.3 

4.4 

5.0 

5.1 

5.2 

5.3 

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

HED Recommendations ..................................... .................................................................. 4 

Tolerance Considerations ................................................................................................ 4 

Label Considerations ....................................................................................................... 5 

Introduction .......................................................................................................................... 5 

Chemical Identity and Physical/Chemical Characteristics ............................................... 5 

Pesticide Use Pattern and Anticipated Exposure Pathways ............................................. 5 

Consideration of Environmental Justice .......................................................................... 8 

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

Summary of Toxicological Effects .................................................................................. 9 

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

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

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

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

Water Residue Profile ....................................................................... ....... ...................... 13 

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

Dietary Exposure and Risk Estimates ............................................................................ 14 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .................................... 14 

6.1 Spray Drift ...................................................................................................................... 14 

6.1. 1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications .............. 15 

6.2 Residential Bystander Post-Application Inhalation Exposure ....................................... 16 

7 .0 Aggregate Exposure/Risk Characterization ....................................................................... 16 

8.0 Cumulative Exposure/Risk Characterization ..................................................................... 16 

9.0 Occupational Exposure/Risk Characterization .................................................................. 17 

9. 1 Occupational Handler Exposure/Risk Estimates ............................................................ 17 

9.2 Occupational Post-application Exposure/Risk Estimates ........................................ ...... 20 

9.2. 1 Occupational Post-application Inhalation Exposure/Risk Estimates ........................... 20 

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates ............................... 20 

l 0.0 Public Health and Pesticide Epidemiology Data ............................................................... 23 

11 .0 Literature References ......................................................................... ................................ 24 

12.0 References .......................................................................................................................... 24 

Appendix A. Toxicology Data Requirements and Toxicology Profile ..................................... 25 

Appendix B. Review of Human Research ................................................... ............................. 29 

Appendix C. Occupational Algorithms ...................... .............. .................................... ............ 30 

Appendix D. Dietary Exposure/Risk Modeling Input and Output ........................................... 33 

Appendix E. Nomenclature and Physical/Chemical Properties ............................................... 35 

Appendix F. Spray Drift Detailed Description ......................................................................... 36 

Page 2 of 37 
Page 3 of 37

1.0 Executive Summary

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

carbonyl]amino]sulfonyl]thiophene-2-carboxylate) is a sulfonylurea herbicide (Group 2) that acts 

through inhibition of the enzyme acetolactate synthase (ALS), affecting cell division and growth 

in plants. It is registered for postemergence application to barley, canola, chicory, cotton, flax, 

field corn, oats, safflower, soybeans, and wheat for selective control of broadleaf weeds. It is also 

registered for use as a preemergence burn-down broadcast application for barley, field corn, oats, 

soybeans, and wheat, and as a preplant burn-down application for canola, cotton, rice, grain 

sorghum, and sugar beets.

In addition to these crop uses, it is also registered for use on agricultural fallow, idle, and 

conservation reserve land. Thifensulfuron methyl is formulated as a dry flowable (DF) and as 

soluble granules (SG). It is applied using common agricultural equipment (i.e., aerial, ground, 

and chemigation). 

Exposure to residues of thifensulfuron methyl may occur via the diet due to its use on food and 

feed crops. Exposures in a residential setting (i.e., non-dietary exposures) are not expected.

A human health scoping document for thifensulfuron methyl was completed in 2011 (D383624, 

D. Dotson). Identified data needs included acute and subchronic neurotoxicity studies in the rat, an 

immunotoxicity study, a 21- or 28-day dermal toxicity study in the rat or rabbit, and a rat 28-day 

subchronic inhalation study. At this time, all of the required studies have been submitted or 

waived, and both the toxicology and exposure databases for thifensulfuron methyl are considered 

complete and adequate for risk assessment. The last human health risk assessment for 

thifensulfuron methyl was conducted in 2012 (D391088, W. Drew). The current draft risk 

assessment incorporates all newly received data and includes updates to hazard and exposure 

assessments, science policies, and procedures. 

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

assessments for thifensulfuron methyl using tolerance-level residues in foods and a sulfonylureaclass-wide screening-level estimate of residues in drinking water. The acute dietary risk estimate 

(females of child-bearing age only) is 3% of the acute population-adjusted dose (PAD), and the 

chronic dietary risk estimates (all population groups) range from 18 to 63% of the chronic PAD; 

all dietary risk estimates are not of concern.

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

with thifensulfuron methyl. Therefore, a quantitative residential exposure assessment was not 

performed. However, thifensulfuron methyl can be applied via groundboom and aerial 

equipment and there is the potential for indirect exposure to residues as a result of spray drift. 

Therefore, HED estimated risks associated with spray drift. The resulting risk estimates are not 

of concern (margins of exposure (MOEs) ≥ 1,300 with a level of concern (LOC) of 100).

Since there are no residential exposure pathways for thifensulfuron methyl, the aggregate 

exposure and risk estimates are equivalent to the dietary exposure and risk estimates and do not 

exceed HED’s level of concern.
Page 4 of 37

No chemical-specific handler exposure data were submitted in support of this draft risk 

assessment; therefore, HED relied on the best available data to assess handler exposure. Default 

assumptions established by HED’s Science Advisory Council for Exposure (ExpoSAC) were 

used for parameters such as body weight and amount handled. All occupational handler scenarios 

for the registered uses resulted in MOEs greater than the LOC of 100 at some level of personal 

protective equipment (PPE) risk mitigation (i.e., anywhere from baseline attire with no chemicalresistant gloves and no respirator to engineering controls) and are not of concern. 

Based on the Agency's current practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment was not performed for thifensulfuron methyl. If new policies or 

procedures are put into place, the Agency may revisit the need for such an assessment. Postapplication dermal exposure and risk estimates for the registered agricultural uses resulted in 

MOEs greater than 100 and are not of concern on day 0 (i.e., 12 hours following application). 

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

acute toxicity of thifensulfuron methyl and is adequate to protect agricultural workers from postapplication exposures.

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

methyl. There are no data gaps that would require submission of additional toxicity, residue 

chemistry, or exposure data.

2.0 HED Recommendations

2.1 Tolerance Considerations

The residue definition for tolerance enforcement is thifensulfuron methyl only. The existing 

tolerances (40 CFR 180.439) are supported by the available residue chemistry data. At this time, 

there are Canadian maximum residue levels (MRLs) for residues of thifensulfuron methyl in 

barley, oats, and wheat at 0.05 ppm; flaxseed and rapeseed at 0.02 ppm; and dry soybeans at 0.1 

ppm. There are no Codex MRLs for thifensulfuron methyl at this time. The U.S. tolerances for 

residues of thifensulfuron methyl are harmonized with Canada. No revisions to the existing U.S. 

tolerances are needed during registration review. 

An analytical reference standard for thifensulfuron methyl is currently available in EPA’s 

National Pesticide Standards Repository (NPSR) and has an expiration date of 19 February 2019

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

required to maintain reasonable amounts of the reference standards for thifensulfuron methyl in 

the NPSR as long as tolerances remain published in 40 CFR §180.439. When necessary, new 

reference standards, or updated certificates of analysis (COAs), should be sent to the Analytical 

Chemistry Branch (ACB), which is located at Fort Meade, MD. It should be sent to the attention 

of either Theresa Cole or Thuy Nguyen at the address listed below, along with a letter of 

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

the registrant. 

 USEPA

 National Pesticide Standards Repository
Page 5 of 37

 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. Safety Data Sheets (SDSs) must accompany all analytical 

standards as specified by the Occupational Safety and Health Administration (OSHA) in 29CFR 

§1910.1200. 

2.2 Label Considerations

PRD should ensure that all labels include the amount of active ingredient per unit of product.

3.0 Introduction

3.1 Chemical Identity and Physical/Chemical Characteristics

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

carbonyl]amino]sulfonyl]thiophene-2-carboxylate) is a sulfonylurea herbicide (Group 2).

The chemical properties of thifensulfuron methyl do not suggest that there are any particular 

exposure issues that warrant special consideration. The compound has a dissociation constant of 

4.0 at 25°C, making its water solubility dependent on pH, with low solubility below pH 3. The 

potential for thifensulfuron methyl to partition into fatty matrices is also, by extension, pH 

dependent; however, based on the octanol/water partitioning coefficients, such partitioning is 

unlikely to occur at physiological pH levels. Thifensulfuron methyl has a relatively low vapor 

pressure, indicating that inhalation of vapors is unlikely to be a significant source of exposure 

under ambient conditions. The nomenclature and physical/chemical properties of thifensulfuron 

methyl are provided in Appendix E.

3.2 Pesticide Use Pattern and Anticipated Exposure Pathways

Thifensulfuron methyl is registered for postemergence application to barley, canola, chicory, 

cotton, flax, field corn, oats, safflower, soybeans, and wheat for selective control of broadleaf 

weeds. It is also registered for use as a preemergence burn-down broadcast application for wheat, 

barley, oats, soybeans, and field corn, and as a preplant burn-down application for canola, cotton, 

rice, grain sorghum, peanuts, and sugar beets. In addition to these crop uses, it is also registered 

for use on agricultural fallow, idle and conservation reserve land. Thifensulfuron methyl is 

formulated as dry-flowable (DF) and soluble-granular (SG) end-use products. There are 4 

actively registered technical products and 48 actively registered end-use products, and they are 

typically applied as preplant or postharvest burn-down, pre-emergence, or post-emergence 

broadcast applications using common agricultural ground or aerial equipment.
Page 6 of 37

The registered use patterns allows one or two application per season; therefore, the duration of 

exposure for occupational handlers is expected to be short-term (i.e., 1 to 30 days) and 

intermediate-term (i.e., 1 to 6 months); long-term exposures (greater than 6 months) are not 

anticipated. The PPE statements on registered labels require applicators, flaggers and other 

handlers to wear the following: long-sleeved shirt, long pants, shoes plus socks, and chemicalresistant gloves. The restricted entry interval (REI) on all labels is 12 hours.

Table 3.2. Summary of Directions for Registered Uses of Thifensulfuron methyl1.

Applic. Timing, 

Type, and Equip.

Formulation and 

Products

[EPA Reg No.]

Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)

Use Directions and 

Limitations

Barley, Wheat

Between 2-leaf and 

flag-leaf stage

Broadcast by ground 

boom, aerial, or 

chemigation

DF, DG, SG, OD

[ 352-446, 352-538, 

352-610, 352-611, 

352-617, 352-633, 

352-641, 352-661, 

352-714, 352-715, 

352-751, 352-876, 

352-896, 352-897, 

352-899]

0.0019-

0.028

1 0.047 45-day PHI for grain

7-day feeding restriction for 

forage

30-day feeding restriction for 

hay

Triticale

Between 2-leaf and 

flag-leaf stage

Broadcast by ground 

boom, aerial, or 

chemigation

DF, DG, SG

[352-446, 352-610, 

352-611, 352-617, 

352-633, 352-641, 

352-661, 352-714, 

352-715, 352-751, 

352-876]

0.0019-

0.028

2 0.047 45-day PHI for grain

7-day feeding restriction for 

forage

30-day feeding restriction for 

hay

Soybean

Preplant or after first 

trifoliate is fully 

expanded

Broadcast by ground 

boom or aerial

DF, DG, SG

[352-446, 352-573, 

352-574, 352-599, 

352-611, 352-633, 

352-661, 352-756, 

352-757, 352-853]

0.0016-

0.023

2 0.023 45-day PHI for grain

7-day feeding restriction for 

forage

30-day feeding restriction for 

hay

Rice

Preplant

Broadcast by ground 

boom or aerial

DF, SG

[352-611, 352-853]

0.0094-

0.021

1 0.021 45-day PHI for grain

7-day feeding restriction for 

forage

30-day feeding restriction for 

hay

Canola, Sugar Beet

60 days preplant

Broadcast by ground 

boom or aerial

DF

[352-611]

0.0094-

0.019

NS 0.031

 

1 The information in this table was supplied by the registrants via the Pesticide Re-Evaluation Division. It has not 

undergone review by the Biological and Economic Analysis Division for completeness or accuracy.
Page 7 of 37

Table 3.2. Summary of Directions for Registered Uses of Thifensulfuron methyl1.

Applic. Timing, 

Type, and Equip.

Formulation and 

Products

[EPA Reg No.]

Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)

Use Directions and 

Limitations

Field Corn

Preplant through 6-

leaf stage

Broadcast by ground 

boom or aerial

DF, DG, SG

[352-446, 352-571, 

352-611, 352-633, 

352-667, 352-721, 

352-759, 352-777, 

352-854]

0.0016-

0.019

2 0.019 45-day PHI for grain

7-day feeding restriction for 

forage

30-day feeding restriction for 

hay

Oats, Sorghum

2-3 leaf stage

Broadcast by ground 

boom, aerial, or 

chemigation

DF, DG, SG, OD

[352-446, 352-538, 

352-611, 352-617, 

352-633, 352-641, 

352-661, 352-714, 

352-876, 352-897, 

352-899]

0.0094-

0.028

1 0.047 45-day PHI for grain

7-day feeding restriction for 

forage

30-day feeding restriction for 

hay

Safflower

Postemergence

Broadcast by ground 

boom or aerial

SG

[352-633]

0141-

0.019

2 0.019 PHI = 81 days

Peanut

Preplant ≥ 45 days 

prior to planting

Broadcast by ground 

boom or aerial

SG

[352-853]

0.016 1 0.016

Cotton

14 days prior to 

planting

Broadcast by ground 

boom or aerial

DF

[352-611, 352-446]

0.0094-

0.016

1 0.016

Chickory

2 true-leaf stage

Broadcast by ground 

boom or aerial

SG

[352-854]

0.0025-

0.005

2 0.005

Preplant Burn-down (Cereals, Sugar Beet, Canola, Corn, Rice, Sorghum, Soybean)

Fall-Spring

Broadcast by ground 

boom or aerial

DF, DG, SG

[352-446, 352-538, 

352-611, 352-617, 

352-633, 352-641, 

352-648, 352-650, 

352-661, 352-714, 

352-749, 352-755, 

352-777, 352-843, 

352-853, 352-876, 

352-877, 352-889, 

352-899]

0.0016-

0.028

3 0.047 Preplant burn-down

After application, allow at 

least: 

14 days before planting 

cotton,

60 days before planting 

sugar beet and canola,

45 days before planting 

other crops.
Page 8 of 37

Table 3.2. Summary of Directions for Registered Uses of Thifensulfuron methyl1.

Applic. Timing, 

Type, and Equip.

Formulation and 

Products

[EPA Reg No.]

Applic. 

Rate

(lb ai/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)

Use Directions and 

Limitations

Fallow, Idle, Conservation Reserve Land†

Spring-Fall

Broadcast by ground 

boom or aerial

DF, DG, SG

[352-446, 352-538, 

352-610, 352-611, 

352-617, 352-633, 

352-641, 352-661, 

352-714, 352-715, 

352-751, 352-759, 

352-777, 352-854, 

352-899]

0.0031-

0.028

3 0.047 Apply to fallow fields when 

the majority of weeds have 

emerged and are actively 

growing.

After application, allow at 

least:

14 days before planting 

cotton,

60 days before planting 

sugar beet and canola,

45 days before planting

other crops.

† Based on information received by BEAD, the thifensulfuron methyl registrations are for use on fallow land. The 

conservation reserve program (CRP) for thifensulfuron methyl is not active; however the use on CRP was assessed 

in this document. There have been no forestry uses of thifensulfuron methyl based on the data available from the US 

Forest Service (2004) and the Bureau of Land Management (2002-2011).

Exposure Pathways

Individuals may be exposed to thifensulfuron methyl via their diet (food and drinking water). 

There are no registered uses for thifensulfuron methyl that will result in direct non-dietary (i.e., 

residential) exposures. However, there is the potential for indirect exposure (incidental oral and 

dermal) to thifensulfuron methyl related to spray drift. Agricultural workers may be exposed to 

thifensulfuron methyl during mixing, loading, and/or applying the herbicide (dermal and 

inhalation routes) as well as during post-application activities (dermal route).

3.3 Consideration of Environmental Justice

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

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

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

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

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

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

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

setting. Extensive data on food consumption patterns are compiled by the 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 
Page 9 of 37

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

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

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

patterns among specific subgroups.

4.0 Hazard Identification/Toxicology

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

The last risk assessment for thifensulfuron methyl was conducted in 2012 (D391088; W. Drew).

In 2011, a scoping document (D383624; W. Drew) was completed which outlined data gaps for 

several toxicity studies as required in accordance with the current Part 158 Guidelines (40 CFR 

Part 158). The studies included dermal and inhalation toxicity, immunotoxicity, and acute and 

subchronic neurotoxicity studies. However, the Hazard and Science Policy Council (HASPOC) 

determined that the dermal and inhalation toxicity studies are not required at this time (TXR# 

0054114) and the immunotoxicity and neurotoxicity studies have since been submitted and 

reviewed. The toxicological endpoints and points of departure (PODs) have been evaluated 

considering the new toxicology data; however, the new studies do not impact the current risk 

assessment. Therefore, the endpoints/PODs selected for risk assessment remain the same as in 

previous assessments. See Appendix A for the thifensulfuron methyl toxicology profile. 

4.1 Summary of Toxicological Effects

Most findings in the submitted studies for thifensulfuron methyl were related to decreases in 

body weights, body weight gains, or organ weights (adrenal, spleen, and thyroid). There were no 

gross or histopathological changes reported in any of the studies. There was also no evidence of 

neurotoxicity or immunotoxicity seen in rat neurotoxicity and immunotoxicity studies. 

Additionally, no evidence of carcinogenicity was observed in the mouse or rat carcinogenicity 

studies. There was no indication of mutagenicity in the battery of available studies. 

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

 

Increased quantitative susceptibility was seen in the rat developmental toxicity study. Decreased 

fetal body weights, and an increased incidence of small renal papillae were observed in fetuses in 

the absence of maternal toxicity. No evidence of increased susceptibility was seen in the rabbit 

developmental or rat reproduction toxicity studies. 

In acute lethality studies, thifensulfuron methyl has low or minimal acute toxicity via the oral 

(category IV), dermal (category III), and inhalation (category III) routes of exposure. It is mildly 

irritating to the eye (category III) and a slight dermal irritant (category IV); it is not a skin 

sensitizer.

Thifensulfuron methyl is rapidly excreted in the urine and feces within 72 hours, with almost no 

tissue or carcass accumulation; most was parent, with five minor metabolites identified. The 

urine was the primary route of excretion. Parent thifensulfuron methyl, at up to 70% of the total 

dose, accounted for the majority of the excreted radioactivity in the urine. Minor metabolites 

were also present at low levels (<3%). The fecal metabolite profile was similar to that for urine. 

Parent thifensulfuron methyl was predominantly seen in feces (up to 17.8%) with the metabolites 
Page 10 of 37

being present in approximately the same percentages as were reported in urine. None of the 

metabolites exceeded 5% of the administered dose. There were no major sex differences 

regarding any aspects of metabolism. 

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

HED recommends that the Food Quality Protection Act Safety Factor (FQPA SF) be reduced to 

1x for thifensulfuron methyl. The toxicology database is complete, and there are no 

concerns/residual uncertainties with regard to pre- and/or postnatal toxicity, and no concern for 

neurotoxicity. Although increased quantitative susceptibility was seen in the rat developmental 

study, concern is low since 1) no developmental effects were seen in the rabbit developmental or 

rat reproduction studies, 2) there are clear NOAELs/LOAELs for the fetal effects observed in the 

rat developmental study, and 3) the endpoints and points of departure selected for risk 

assessment are protective of the effects observed in the study. 

4.3 Toxicity Endpoint and Point of Departure Selections

The toxicological endpoints and points of departure (PODs) used for risk assessment have been 

re-evaluated considering new toxicology data; however, the new data do not alter the PODs 

previously selected. However, in order to evaluate non-occupational exposures from spray drift, 

incidental oral and dermal PODs were selected from the thifensulfuron methyl database. 

The acute dietary risk assessment is for females of child-bearing age only, and it is currently 

based on decreased body weight and increased incidence of small renal papillae. The endpoint

was previously selected to be protective of the developing fetus since the effect was observed in 

the absence of maternal toxicity. It should be noted that this approach is considered very 

conservative; however, HED did not update/change the existing acute dietary endpoint for the 

draft risk assessment. Also, the endpoints and PODs presented in the toxicology profile table 

(Appendix A) have not been updated to comply with current policy regarding what constitutes an 

adverse effect. The NOAELs and LOAELS have not been changed. Therefore, the 

endpoints/PODs selected for risk assessment may be conservative. The PODs selected for risk 

assessment are protective of the effects observed in the thifensulfuron methyl database. A 

summary of toxicological doses and endpoints used in the thifensulfuron methyl human health 

risk assessments is presented below:

Table 4.3.1. Summary of Thifensulfuron Methyl Doses and Endpoints for Use in Dietary and NonOccupational Risk Assessments. 

Exposure/

Scenario

Point of Departure Uncertainty/

FQPA Safety 

Factors

LOC for Risk 

Assessment

Study and Toxicological 

Effects

Acute dietary

(females 13-49 

only)

NOAEL = 159

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1

aRfD = 1.59 

mg/kg/day

aPAD = 1.59 

mg/kg/day

Developmental oral toxicity in 

rats. LOAEL = 725 mg/kg/day, 

based on decreased mean body 

weight, and increased 

incidence of small renal 

papillae. 
Page 11 of 37

Table 4.3.1. Summary of Thifensulfuron Methyl Doses and Endpoints for Use in Dietary and NonOccupational Risk Assessments. 

Exposure/

Scenario

Point of Departure Uncertainty/

FQPA Safety 

Factors

LOC for Risk 

Assessment

Study and Toxicological 

Effects

Chronic dietary

(all populations)

NOAEL = 4.3

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1

cRfD = 0.043 

mg/kg/day

cPAD = 0.043 

mg/kg/day

Carcinogenicity oral toxicity in 

mice. 

LOAEL = 128 mg/kg/day, 

based on decreased body 

weight and body weight gain. 

Incidental oral 

(short-term)

NOAEL = 7 mg/kg/day UFA = 10X

UFH = 10X

FQPA SF = 1

MOE = 100 90-Day Oral Toxicity in Rats.

LOAEL = 177 mg/kg/day 

based on decreased body 

weight and body weight gain in 

males and females and 

decreased spleen weights in 

males.

Dermal short-

(1-30 days) and 

intermediateterm (1-6 

months)

NOAEL = 7 mg/kg/day 

(default DAF of 100%)

UFA = 10X

UFH = 10X

FQPA SF = 1

MOE = 100 90-Day Oral Toxicity in Rats.

LOAEL = 177 mg/kg/day 

based on decreased body 

weight and body weight gain in 

males and females and 

decreased spleen weights in 

males.

Cancer (oral) Not likely to be a human carcinogen, based on the lack of evidence of carcinogenicity in rats 

and mice.

Point of Departure (POD) = a data point or estimated point derived from observed dose-response data, which is used 

to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. UF = Uncertainty Factor. UFA = extrapolation from animal to human (interspecies). UFH = potential 

variation in sensitivity among members of the human population (intra-species). FQPA SF = FQPA Safety Factor. 

NOAEL = No Observed Adverse Effect Level. LOAEL = Lowest Observed Adverse Effect Level. PAD = 

Population Adjusted Dose (a = acute, c = chronic). RfD = Reference Dose.

Table 4.3.2. Summary of Thifensulfuron Methyl Doses and Endpoints for Use in Occupational Risk 

Assessments.

Exposure/

Scenario

Point of Departure Uncertainty/

FQPA Safety

Factors

LOC for Risk 

Assessment

Study and Toxicological 

Effects

Dermal short-

(1-30 days) and 

intermediateterm (1-6 

months)

NOAEL = 7 mg/kg/day 

(default DAF of 100%)

UFA = 10X

UFH = 10X

MOE = 100 90-Day Oral Toxicity in Rats.

LOAEL = 177 mg/kg/day 

based on decreased body 

weight and body weight gain in 

males and females and 

decreased spleen weights in 

males.

Inhalation short-

(1-30 days) and 

intermediateterm (1-6 

months)

NOAEL = 7 mg/kg/day UFA = 10X

UFH = 10X

MOE = 100 90-Day Oral Toxicity in Rats.

LOAEL = 177 mg/kg/day 

based on decreased body 

weight and body weight gain in 

males and females and 

decreased spleen weights in 

males.

Point of Departure (POD) = a data point or estimated point derived from observed dose-response data, which is used 

to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. UF = Uncertainty Factor. UFA = extrapolation from animal to human (interspecies). UFH = potential 
Page 12 of 37

variation in sensitivity among members of the human population (intra-species). FQPA SF = FQPA Safety Factor. 

NOAEL = No Observed Adverse Effect Level. LOAEL = Lowest Observed Adverse Effect Level. PAD = 

Population Adjusted Dose (a = acute, c = chronic). MOE = Margin Of Exposure. LOC = Level Of Concern. 

4.4 Endocrine Disruptor Screening Program

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

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

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

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

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

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

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

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

taxonomic groups. As part of its most recent registration decision for thifensulfuron 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), 

thifensulfuron 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, 20132and 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.3

 

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

chemicals.

3 http://www.epa.gov/endo/
Page 13 of 37

5.0 Dietary Exposure and Risk Assessment 

5.1 Water Residue Profile

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

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

(SU) dietary risk assessments. Rather than produce chemical-specific estimated drinking water 

concentrations (EDWCs) following the usual assessment procedures, EFED provided coarsescreen estimates that should exceed upper-bound, chemical-specific EDWCs for any SU. This 

was achieved by using model inputs that represent the use pattern of highest exposure from any 

SU, the highest soil mobility of any SU residue of concern, and the highest persistence to any 

route of degradation over time. The resulting coarse-screen EDWCs from PRZM-GW were used 

as conservative estimates of exposure and are summarized in Table 5.1 (D427429, G. Orrick). 

The acute and chronic dietary assessments for thifensulfuron methyl used the coarse-screen 

maximum daily concentration of 751 μg/L (0.751 ppm) and the post-breakthrough mean value of 

492 μg/L (0.492 ppm), respectively. 

Table 5.1. PRZM-GW Coarse-Screen EDWCs for Sulfonylureas1.

Modeled Scenario Kd or KOC

Initial Application 

Dates (days postemergence)

Max. Daily Conc. 

(μg/L)

Mean 

Breakthrough 

Time (yrs)

Postbreakthrough 

Mean (μg/L)

WI corn Kd 7 449 11.5 415

KOC 7 504 6.9 425

DMV corn Kd 7 489 5.3 369

KOC 7 560 3.3 378

FL citrus Kd 7 429 3.2 351

KOC 7 467 2.3 349

FL potato Kd 7 375 2.6 272

KOC 7 407 2.2 275

GA peanut Kd 7 197 5.2 156

KOC 7 206 3.9 158

NC cotton Kd 7 640 8.7 492

Kd 37 641 8.7 491

Kd 67 637 8.7 490

KOC 7 742 5.7 484

KOC 37 751 5.7 483

KOC 67 744 5.7 482

1 Maximum values are bolded.

5.2 Food Residue Profile 

The residue chemistry database for thifensulfuron methyl is considered to be complete and no 

additional data are required at this time. The residue of concern for dietary risk assessment of 

thifensulfuron methyl is the parent compound itself. In conducting this assessment, HED has 
Page 14 of 37

assumed tolerance-level residues in the raw agricultural commodities and processed products of 

registered crops, and that 100 percent of those crops are treated with thifensulfuron methyl.

5.3 Dietary Exposure and Risk Estimates

New dietary exposure and risk estimates were obtained for this assessment in order to 

incorporate the new EDWCs (see Section 5.1). The exposure and risk estimates were made using

the Dietary Exposure Evaluation Model using the Food Commodity Intake Database (DEEMFCID; version 3.18). The model uses food consumption data from the 2003-2008 

NHANES/WWEIA database, coupled with recipe files and residues in foods, to derive estimates 

of dietary exposure and risk. Generally, HED is concerned when dietary exposure estimates 

exceed 100% of the population adjusted dose (PAD). In the case of thifensulfuron methyl, the 

dietary risk estimates (Table 5.3) are not of concern. The acute estimate is 2.6% of the aPAD for 

women of child-bearing age at the 95th percentile, and the chronic estimates range from 18 to 

63% of the cPAD across all representative population groups. Because of the very conservative 

assumptions used in the analysis (tolerance-level residues, 100 % crop treated, upper-bound 

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

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

Appendix D. 

Table 5.3. Summary of dietary exposure and risk estimates for thifensulfuron methyl.

Acute Estimates (95th Percentile) Chronic Estimates

Population Group

Exposure, 

mg/kg bw Risk, % aPAD

Exposure, 

mg/kg bw/day Risk, % cPAD

Total US Population

Not Applicable Not Applicable

0.0105 24

All Infants (< 1 year old) 0.0270 63

Children 1-2 years old 0.0154 36

Children 3-5 years old 0.0131 30

Children 6-12 years old 0.0094 22

Youth 13-19 years old 0.0077 18

Adults 20-49 years old 0.0105 24

Adults 50-99 years old 0.0103 24

Female 13-49 years old 0.0412 2.6 0.0104 24

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no registered residential uses resulting in residential exposure associated with 

thifensulfuron methyl. Therefore, a quantitative residential exposure assessment was not 

performed.

6.1 Spray Drift

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

associated risks is available in Appendix F.
Page 15 of 37

6.1.1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications

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

result of the screening level agricultural application scenarios. The potential risk estimates from 

these residues can be calculated using drift modeling onto 50 feet wide lawns coupled with 

methods employed for residential risk assessments for turf products. 

Thifensulfuron methyl is registered for use on cereal grains (barley, field corn, oats, rice, 

sorghum, wheat, and triticale), oilseed crops (canola, rape, and flax), soybeans, sugar beets, 

cotton, and chicory. In addition to these crop uses, it is also registered for use on agricultural 

fallow, idle, and conservation reserve land. Corn, wheat, sorghum, and cotton are the 

predominant registered agricultural usage crops; therefore, they are considered representative of 

the registered uses. The recommended drift scenario screening level options are listed below:

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

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

• Aerial applications are based on the use of AgDrift Tier 1 aerial option for a fine to 

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

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

event). 

• Airblast applications are based on the AgDrift option for Sparse (Young/Dormant) tree 

canopies.

The spray drift assessment is based on dermal and incidental oral exposures. The highest 

exposure resulted from drift following thifensulfuron methyl applications using aerial equipment 

for children 1 to <2 years old (combined dermal + incidental oral MOEs ≥ 1,300, with a LOC

=100). There are no risks of concern at the field’s edge (i.e., assuming a residential lawn is 

directly adjacent to a field where agricultural crops are grown and treated with aerial, 

groundboom or airblast equipment). See Tables 6.1.1 and 6.1.2 for detailed results.

1 HED’s default assumption that 10% of the application is available for transfer on day 0 following the application and the 

residues dissipate at a rate of 10% each following day.

Table 6.1.1. Adult Risk Estimates (MOEs) Related to Dermal Exposure to Spray Drift from Thifensulfuron methyl.

Crop/Rate 

Group Spray Type/ Nozzle Configuration Appl. Rate (lb ai/A) TTR1

(ug/cm2) At Edge of the Field

Dermal

Aerial Fine to Medium

0.028 0.0031

2,600

Groundboom High Boom Very fine to Fine 3,600

Airblast Sparse 4,600

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

from Thifensulfuron methyl.

Crop/Rate 

Group Spray Type/ Nozzle Configuration Appl. Rate (lb ai/A) TTR1

(ug/cm2) At Edge of the Field

Dermal & Incidental Oral (Combined)

Aerial Fine to Medium

0.028 0.0031

1,300

Groundboom High Boom Very fine to Fine 1,800

Airblast Sparse 2,300
Page 16 of 37

1 HED’s default assumption that 10% of the application is available for transfer on day 0 following the application and the 

residues dissipate at a rate of 10% each following day.

6.2 Residential Bystander Post-Application Inhalation Exposure

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

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

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

(FIFRA) 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.

4

 During Registration Review, the Agency will 

use this analysis to determine if data (i.e., flux studies, route-specific inhalation toxicological 

studies) or further analyses are required for thifensulfuron methyl.

7.0 Aggregate Exposure/Risk Characterization

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

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

there is reliable information. In the case of thifensulfuron methyl, aggregate exposure and risk 

estimates are equivalent to the dietary exposure and risk estimates in Section 5.3, above, and are 

not of concern.

8.0 Cumulative Exposure/Risk Characterization

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

Cumulative Risk Assessment: Framework for Screening Analysis 

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

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

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

framework supplements the existing guidance documents for establishing common mechanism 

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

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

D428798; 9/9/15). Although the SUs share some chemical and toxicological characteristics, the 

toxicological database does not support a testable hypothesis for a common mechanism of action. 

No further mechanistic data are required and no further cumulative evaluation is necessary.

 

4 Available at: http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219.

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

(USEPA, 1999)

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

(USEPA, 2002)
Page 17 of 37

9.0 Occupational Exposure/Risk Characterization

9.1 Occupational Handler Exposure/Risk Estimates

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

occupational handler exposure is expected from the registered uses. Therefore, as part of this 

assessment, HED re-evaluated occupational exposures in order to ensure that the estimates 

reflect the most recent policies and procedures. The quantitative exposure/risk assessment 

developed for occupational handlers is based on the scenarios listed in Table 9.1. Based on the 

use pattern and agricultural practices, occupational exposures from the registered food uses are

expected to be short-term (1-30 days) and intermediate-term (i.e., 1-6 months) in duration. Since 

the same endpoint and point of departure were selected for short- and intermediate-term 

durations, short-term exposure and risk estimates are considered to be protective of intermediateterm exposure and risk. Long-term exposures (i.e., more than 6 months) are not anticipated.

Occupational Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational 

handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate: The maximum single application rates are listed in Table 3.2. Refer to section 

3.0 for a complete use pattern description.

Body Weight: The standard body weight for the general population (80 kg) was used for all 

dermal and inhalation exposure scenarios covered in this risk assessment because the endpoint 

selected was not developmental or based on fetal effects. 

Absorption Factor: Since no inhalation absorption data are available, toxicity by the inhalation 

route is considered to be equivalent to the estimated toxicity by the oral route of exposure. A 

dermal absorption factor of 100% was used for the exposure assessment since dermal absorption 

data are not available for thifensulfuron methyl. 

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

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

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

Exposure Task Force (AHETF) database. Some of these data are proprietary (e.g., AHETF data), 

and subject to the data protection provisions of FIFRA. The standard values recommended for 

use in predicting handler exposure that are used in this assessment, known as “unit exposures”, 

are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table7.” 

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

at the Agency website8. 

Area Treated or Amount Handled: The inputs for area treated or amount handled were based on 

the Science Advisory Council for Exposure Policy 9.1: Standard Values for Daily Acres Treated 

 

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

8 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Page 18 of 37

in Agriculture (values are listed in Table 9.1). The acres treated for high acreage crops for aerial 

and groundboom applications, and orchard/vineyards for airblast applications were used as 

screening for the occupational assessment.

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

occupational handlers can be found in Appendix C.

Combining Exposures/Risk Estimates: Dermal and inhalation risk estimates were combined in 

this assessment since the toxicological effects for these exposure routes were similar and based 

on the same POD and study. Dermal and inhalation risk estimates were combined using the 

following formula:

Total MOE = Point of Departure (mg/kg/day) ÷ Combined Dermal + Inhalation Dose 

(mg/kg/day)

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimate

The exposure scenarios presented in Table 9.1 are considered protective of all existing uses. All 

occupational handler scenarios for the registered uses resulted in total MOEs greater than 100 at 

baseline level of risk mitigation (i.e., baseline attire with no gloves or respirator), baseline attire 

with chemical-resistant gloves or engineering controls (i.e., enclosed systems or enclosed 

cockpits for aerial applications) and, therefore, are not of concern. The lowest MOE (240) is 

associated with total exposure during mixing/loading activities for a dispersible granule 

formulation being applied to 350 acres using chemigation equipment. All other MOEs were 

higher, ranging from 270 to 8,000.

The Agency matches quantitative occupational exposure assessment with appropriate 

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

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

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

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

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

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

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

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

applications.

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

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

engineering control (i.e., enclosed cockpits) and baseline attire (i.e., long-sleeve shirt, long pants, 

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

controls, pilots are not required to wear protective gloves for the duration of the application. 

With this level of protection, there are no risk estimates of concern for applicators.
Page 19 of 37

Table 9.1. Short-term Handler Exposure and Risk Estimates for Thifensulfuron methyl.

Exposure Scenario Unit Exposure

(ug/lb ai)

[Mitigation Level]ab

Application 

Rate

(lb ai/A)c

Area 

Treated 

(Acres)d

Dermal Inhalation Total

MOEi

Dermal Inhalation Dose, 

mg/kg/daye

MOEf Dose, 

mg/kg/dayg

MOEh

Mixer/Loader

Dry Flowable 

(Dispersible Granule) 

for Aerial Application

51.6 

(Baseline, 

Gloves)

8.96

(No respirator)

0.028 1,200 0.0218 320 0.00378 1,900 270

Dry Flowable 

(Dispersible Granule) 

for Groundboom 

Application

227 

(Baseline)

8.96

(No respirator)

0.028 200 0.0160 440 0.00063 11,000 420

Dry Flowable 

(Dispersible Granule) 

for Airblast 

Application

227 

(Baseline)

8.96

(No respirator)

0.028 40 0.00319 2,200 0.000126 56,000 2,100

Dry Flowable 

(Dispersible Granule) 

for Chemigation 

Application

227 

(Baseline)

8.96

(No respirator)

0.028 350 0.0279 250 0.0011 6,400 240

Applicator

Sprays for Aerial 

Application

2.08

(Engineering 

Controls –

Enclosed 

Cockpit)

0.0049

(Engineering 

Controls –

Enclosed 

Cockpit)

0.028 1,200 0.00088 8,000 0.0000021 3,400,000 8,000

Sprays for 

Groundboom 

Application

78.6 

(Baseline)

0.34

(Baseline)

0.028 200 0.00553 1,300 0.0000239 290,000 1,300

Sprays for Airblast 

Application

1,770 

(Baseline)

4.71

(Baseline)

0.028 40 0.02490 280 0.0000661 110,000 280

Flagger

Sprays for Aerial 

Application

11

(Baseline)

0.35

(Baseline)

0.028 350 0.00135 5,200 0.000043 160,000 5,000

a. Mitigation Level: “baseline” (i.e., single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no 

gloves, and no respirator); “engineering controls for aerial applications” (i.e., enclosed cockpit).

b. Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (February, 2015).

c. Based on the maximum single application rates listed on registered labels (Table 3.2).

d. Based on the Science Advisory Council for Exposure Policy 9.1: Standard Values for Daily Acres Treated in Agriculture.

e. Dermal Dose (mg/kg/day) = [Rate x UE x 0.001 x Dermal Absorption (100%) x Acres Treated or Amount Handled]/BW (80

kg). 

f. Dermal MOE = Dermal NOAEL (mg/kg/day)/ Dermal Dose (mg/kg/day). LOC=100.

g. Inhalation Dose (mg/kg/day) = [Rate x UE x 0.001 x Acres Treated or Amount Handled]/BW (80 kg).

h. Inhalation MOE = Inhalation NOAEL (mg/kg/day)/ Inhalation Dose (mg/kg/day). LOC=100.

i. Total MOE = NOAEL (mg/kg/day)/ [Dermal Dose + Inhalation Dose (mg/kg/day)]. LOC=100.

j. At baseline PPE, the dermal MOE is 51 and is of concern.
Page 20 of 37

9.2 Occupational Post-application Exposure/Risk Estimates

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

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

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

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

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

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

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

the same endpoint and point of departure were selected for short- and intermediate-term 

durations, short-term exposure and risk estimates are considered to be protective of intermediateterm exposure and risk.

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates

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

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

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

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency has 

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

Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the Agency will use this analysis to determine if 

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

required for thifensulfuron methyl.

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

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

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

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

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

performed, an inhalation exposure assessment was performed for occupational handlers. Handler 

exposure resulting from application of pesticides outdoors is likely to result in higher exposure 

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

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

scenarios.

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

A series of assumptions and exposure factors served as the basis for completing the occupational 

post-application dermal risk assessment, including the following:
Page 21 of 37

Exposure Duration: Based on the use pattern and agricultural practices, occupational postapplication exposure from the registered food uses is expected to be short-term (1-30 days) and 

intermediate-term (i.e., 1-6 months) in duration. Since the same endpoint and point of departure 

were selected for short- and intermediate-term durations, short-term exposure and risk estimates 

are considered to be protective of intermediate-term exposure and risk. Long-term exposures 

(i.e., more than 6 months) are not anticipated.

Transfer Coefficients: It is the policy of HED to use the best available data to assess postapplication exposure. Sources of generic post-application data, used as surrogate data in the 

absence of chemical-specific data, are derived from the Agricultural Reentry Task Force (ARTF)

exposure monitoring studies, and, as proprietary data, are subject to the data protection 

provisions of FIFRA. The standard values recommended for use in predicting post-application 

exposure that are used in this assessment, known as “transfer coefficients”, are presented in the 

ExpoSAC Policy 39” which, along with additional information about the ARTF data, can be 

found at the Agency website10. Table 9.2.2.1 provides a summary of the anticipated postapplication activities and associated transfer coefficients for the proposed crops/use sites.

Table 9.2.2.1. Anticipated High-contact Post-Application Activities and Dermal Transfer Coefficients.

Proposed Crops

Policy Crop 

Group 

Category

Crop 

Height

Foliage 

Density

Transfer 

Coefficients 

(cm2/hr)

Activities

Corn Field, row, 

tall High Full 1,900 Irrigation (Hand set)

Barley, Wheat Field, row, 

medium Low Full 1,100 Scouting

Safflower Field, row, 

medium Low Full 1,900 Irrigation (Hand set)

Beets, Sugar Field, row, 

medium Low Full 1,100 Hand, Harvesting

Soybean Field, row, 

medium Low Full 1,100 Scouting

Sorghum Field, row, 

tall High Full 210 Scouting

Application Rate: The maximum single application rates are listed in Table 3.2. Refer to section 

3.0 for a complete use pattern description.

Exposure Time: The average occupational workday is assumed to be 8 hours. 

Dislodgeable Foliar Residues: Chemical-specific dislodgeable foliar residue data have not been 

submitted for thifensulfuron methyl during registration review. This assessment uses HED’s 

default assumption that 25% of the application is available for transfer on day 0 following the 

application and the residues dissipate at a rate of 10% each following day.

 

9 Available: http://www.epa.gov/pesticides/science/exposac_policy3.pdf

10 Available: http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Page 22 of 37

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

occupational post-application workers can be found in Appendix C.

Occupational Post-application Non-Cancer Dermal Risk Estimates

A summary of the post-application exposure and risk estimates for the registered uses is provided 

in Table 9.2.2.2. Only risk estimates for the highest contact activity for each crop and the highest 

application rates are shown below. This dermal post-application assessment is considered 

conservative because thifensulfuron methyl is mainly applied during pre-pant or at planting. 

Post-application dermal exposure and risk estimates for the scenarios shown below resulted in 

MOEs greater than 100 and are not of concern on day 0 (i.e., 12 hours following application). All 

other scenarios involving lower contact activities and lower foliage/crop height would have 

higher MOEs and are also not of concern.

A summary of the post-application dermal exposure and risk estimates from use of 

thifensulfuron methyl on cotton during harvesting activities is provided in Table 9.2.2.3. 

Thifensulfuron methyl is applied on cotton either 13-22 days prior to planting or at planting, 

leaving a 5-month period between application and harvest. Dislodgeable residue data for cotton 

bolls were not available for thifensulfuron methyl; therefore, the dislodgeable residue value for 

cotton bolls was estimated from the field trial residues in/on cotton gin byproducts. The field trial 

residue is an upper-bound residue value collected at the pre-harvest interval which represents the 

amount of residue in and on the cotton boll, not just the amount of residue that could be 

dislodged. It is considered appropriate as an estimate of dislodgeable boll residue, and is used as 

a screening level approach to estimating exposure. Furthermore, in the case of thifensulfuron 

methyl, residues in cotton gin byproducts were below the analytical method limits of 

quantification (LOQ; 0.02 mg ai/kg) and detection (LOD; 0.006 mg ai/kg) in all samples.

Therefore, the 0.02-mg/kg residue estimate used in the post-application dermal risk assessment 

for use on cotton is very conservative and results in exposure estimates that are likely to 

significantly overestimate actual exposures for that scenario. Post-application dermal exposure 

and risk estimates resulted in MOEs greater than 100 and are not of concern.

Table 9.2.2.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Thifensulfuron

Methyl

Crop/Site Activities Transfer Coefficient 

(cm2/hr) DFR1 Dermal Dose (mg/kg/day)2 MOE3

Short- and Intermediate-term

Corn Irrigation (Hand 

set) 1,900 0.08 0.015 470

Barley, Wheat Scouting 1,100 0.08 0.009 810

Safflower Irrigation (Hand 

set) 1,900 0.08 0.015 470

Beets, Sugar Hand, Harvesting 1,100 0.08 0.009 810

Soybean Scouting 1,100 0.08 0.009 810

Sorghum Scouting 210 0.08 0.002 4,200

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

2. Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × Dermal Absorption (100%)]  BW (kg).
Page 23 of 37

3. MOE = Dermal NOAEL (7 mg/kg/day) / Dermal Dose (mg/kg/day); LOC=100. 

Table 9.2.2.3. Post-Application Exposure and Risk Estimates for use of Thifensulfuron Methyl on Cotton during 

Harvesting Activities.

Crop

Maximum 

Seasonal 

Application 

Rate

(lb ai/A)

Activity TC1

(g cotton/hr)

Days After 

Treatment

Residue from 

Cotton Field 

Trial 2

(mg ai/g 

cotton)

Daily Dose 

(mg/kg/d)3 MOE4

Short- and Intermediate-term

Cotton 0.025

Harvesting 

Mechanical 

(Module Builder)

900

123 0.00002

0.0018 3,900

Harvesting 

Mechanical (Picker 

Operator; Raker)

2400 0.0048 1,400

Harvesting 

Mechanical 

(Tramper)

5050 0.0101 690

1. Transfer Coefficients from HED Policy No. 3.0., Non-Foliar Transfer Coefficient Table, March 2012 (p 122). 

2. Residue Value from Cotton Field Trial (mg ai/g cotton) = (0.02 mg ai/kg cotton) (0.001 kg/g) = 0.00002 mg ai/g cotton.

3. Dermal Dose (mg/kg/day) = [Cotton Field Trial Residue Value adjusted (mg ai/g cotton) x TC (g cotton/hr) x hr/day (8 

hrs/day) x DAF (100%)]/ BW (80 kg).

4. Dermal MOE = NOAEL (7 mg/kg/day)/Dermal Dose (mg/kg/day); LOC = 100.

Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of thifensulfuron methyl. 

Thifensulfuron methyl is classified as Toxicity Category III via the dermal route and Toxicity 

Category IV for skin irritation potential. It is not a skin sensitizer. Short- and intermediate-term 

post-application risk estimates were not a concern on day 0 (i.e., 12 hours following application) 

for all post-application activities. Under 40 CFR 156.208 (c) (2) (iii), ai’s classified as Acute 

Toxicity Category III or IV for acute dermal, eye irritation, and primary skin irritation are 

assigned a 12-hour REI. Therefore, the [156 subpart K] Worker Protection Statement interim 

REI of 12 hours is adequate to protect agricultural workers from post-application exposures to 

thifensulfuron. 

10.0 Public Health and Pesticide Epidemiology Data

D425818, S. Recore, 24 March 2015

Thifensulfuron methyl was previously reviewed in 2010 (D383694, S. Recore, 11/30/2010). At 

the time, there were no thifensulfuron methyl incidents found in the Main Incident Data System 

(IDS) and 12 incidents reported to Aggregate IDS. Upon review of these incidents, it was 

concluded that “Based on the low frequency and severity of incident cases, there does not appear 

to be a concern at this time that would warrant further investigation.” 

The current IDS analysis from January 1, 2010 through March 10, 2015, shows 1 incident 

reported involving thifensulfuron methyl in Main IDS involving multiple chemicals and five 

incidents reported to Aggregate IDS. Further, a query of SENSOR-Pesticides 1998-2011 

identifies nine cases involving multiple active ingredients. These incidents were classified as low 

severity.
Page 24 of 37

Based on the low frequency and mostly low severity of incident cases reported for thifensulfuron 

methyl in both IDS and NIOSH SENSOR-Pesticides, there does not appear to be a concern at 

this time that would warrant further investigation. The Agency will continue to monitor the 

incident information and if a concern is triggered, additional analysis will be conducted.

The Agricultural Health Study (AHS) is also a potential source of information pertaining to

human health effects associated with certain pesticides. Thifensulfuron methyl is not included in 

the AHS; therefore, the AHS does not provide information relevant to this assessment.

11.0 Literature References

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

information that would impact the current risk assessment. 

12.0 References

Author Barcode Date Title

Drew, W. D361902 29 Jan 2010 Thifensulfuron Methyl. Human Health Risk 

Assessment for the Proposed Food/Feed Use of the 

Herbicide (Associated with Regional Section 3 

Registration) on Safflower.

Dotson, D. D383624 15 Mar 2011 Thifensulfuron Methyl. Human Health Assessment 

Scoping Document in Support of Registration 

Review.

Recore, S. D383694 30 Nov 2010 Thifensulfuron Methyl: Review of Human Incidents

Drew, W. D391088 1 Jun 2012 Thifensulfuron Methyl. Human Health Risk 

Assessment for the Proposed Use of the Herbicide 

on Chicory.

Recore, S. D425818 24 Mar 2015 Thifensulfuron Methyl: Tier 1 Update Review of 

Human Incidents/Epidemiology for Draft Risk 

Assessment

Smegal, D. TXR# 0054114 7 Mar 2012 Thifensulfuron Methyl: Summary of Hazard and 

Science Policy Council (HASPOC) Meeting of 

February 23, 2012: Recommendations on the need 

for 28-day inhalation and 28-day dermal toxicity 

studies.

Orrick, G. D427429 12 Dec 2015 Drinking Water Exposure assessment for the 

Registration Review of 22 Sulfonylurea Herbicides
Page 25 of 37

Appendix A. Toxicology Data Requirements and Toxicology Profile 

A.1. Toxicity Requirements

The toxicology requirements (40 CFR 158.340) for thifensulfuron methyl are presented below.

TABLE A.1 Toxicology Data Requirements for Thifensulfuron Methyl.

Test 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 (Non-Rodent)....................................................

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

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

870.3465 21/90 -Day Inhalation..................................................................

yes

yes

yes

no

no

yes

yes

no*

no

no*

870.3700a Developmental Toxicity (Rodent) ...............................................

870.3700b Developmental Toxicity (Non-Rodent).......................................

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

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (Rodent)...........................................................

870.4100b Chronic Toxicity (Non-Rodent) ..................................................

870.4200a Oncogenicity (Rat).......................................................................

870.4200b Oncogenicity (Mouse) .................................................................

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

yes

yes

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.................

870.5395 Mutagenicity – Mammaliam Erythrocyte Micronucleus.............

870.5550 Mutagenicity – Unscheduled DNA Synthesis .............................

870.5915 Mutagenicity – In Vivo Sister Chromatid Exchange....................

yes

yes

yes

no

no

no

yes

yes

yes

yes

yes

no

870.6100a Acute Delayed Neurotoxicity (Hen) ............................................

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

870.6200a Acute Neurotoxicity Screening Battery (Rat)..............................

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

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

no

no

yes

yes

no

no

no

yes

yes

no

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

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

yes

no

yes

no

870.7800 Immunotoxicity Yes yes

* The Hazard and Science Policy Council (HASPOC) determined that subchronic dermal and inhalation toxicity studies are not 

required.
Page 26 of 37

A.2. Toxicity Profiles

TABLE A.2.1 Acute Toxicity Profile for Technical Thifensulfuron Methyl. 

Guideline 

Number

Study Type MRID 

Number

Results Tox

Category

870.1100 Acute Oral - Rat 00146033 LD50 >5000 mg/kg (M+F) IV

870.1100 Acute Oral - Rat 00146034 LD50 >5000 mg/kg (M+F) IV

870.1200 Acute Dermal 00146035 LD50 >2000 mg/kg (M+F) III

870.1200 Acute Dermal 40467606 LD50 >2000 mg/kg (M+F) III

870.1300 Acute Inhalation 00143657 LC50 >7.9 mg/L/4 hours IV

870.2400 Primary Eye Irritation 00143658 Moderate irritation. III

870.2500 Primary Skin Irritation 40921502 Slight irritation. IV

870.2600 Dermal Sensitization 00146037 Not a sensitizer. NA*

* NA = Not Applicable. 

TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Thifensulfuron Methyl. 

Guideline

Number

Study Title MRID Number Results

870.3100 90-Day Oral 

Toxicity - Rat 

(diet)

00143660 (1984)

Acceptable/guideline

ppm = 0, 100, 2500, & 

7500

mg/kg/day (M/F) = 0/0,

7/9, 177/216, 559/697

NOAEL = 7 (males), 9 (females) mg/kg/day.

LOAEL = 177 (males), 216 (females) mg/kg/day, 

based on decreased body weight, body weight gain, 

and spleen weight in males only (13%).

870.3100 90-Day Oral 

Toxicity- Mouse 

(diet)

00161276 (1984)

Acceptable/guideline

ppm=0, 500, 2500 & 

7500

mg/kg/day (M/F) = 0/0, 

97/123, 523/690 & 

1427/2287

NOAEL = 1427 (males), 2287 (females) 

mg/kg/day.

LOAEL = could not be determined.

870.3150 13-Week Oral 

Toxicity- Dog 

(diet)

00145160 (1984)

Acceptable/guideline

ppm = 0, 75, 1500 & 

7500 

mg/kg/day (M&F) = 0, 

1.88, 37.5 & 187.5 

NOAEL = 37.5 males & females mg/kg/day.

LOAEL = 187.5 males & females mg/kg/day, based 

on decreased body weight and adrenal weight in 

high-dose males.

870.3200 21/28-Day 

Dermal Toxicity 

– Rat

Waived by HASPOC (TXR# 0054114)

870.3465 21/90 -Day 

Inhalation

Waived by HASPOC (TXR# 0054114)

870.3700a Developmental 

Toxicity- Rat 

(gavage)

00143661 (1984)

Acceptable/guideline

mg/kg/day = 0, 26, 159, 

& 725 (analytically 

determined doses)

Maternal NOAEL = 725 mg/kg/day.

LOAEL = could not be determined.

Developmental NOAEL = 159 mg/kg/day.

LOAEL = 725 mg/kg/day, based on decreased 

mean fetal body weights, and increased incidence 

of small renal papillae.

870.3700b Developmental 

Toxicity- Rabbit 

(gavage)

00161277 (1984)

Acceptable/guideline

mg/kg/day = 0, 22, 158 

& 511 (analytically 

determined doses)

Maternal NOAEL = 158 mg/kg/day.

LOAEL = 511 mg/kg/day, based on decreased 

mean body weights.

Developmental NOAEL = 511 mg/kg/day.

LOAEL = could not be determined.

870.3800 Reproduction (2- 00161278 (1985) Parental/Systemic NOAEL = 175 (males), 244 
Page 27 of 37

TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Thifensulfuron Methyl. 

Guideline

Number

Study Title MRID Number Results

Generation) – Rat 

(diet)

Acceptable/guideline

ppm = 0, 25, 500 & 

2500

mg/kg/day F0 M/F = 

0/0, 1.8/2.4, 34/48 & 

175/244

mg/kg/day F1b M/F = 

0/0, 1.7/2.1, 36/43 &

180/212

(females) mg/kg/day.

LOAEL = could not be determined.

Reproductive NOAEL = 180 (males), 212 

(females) mg/kg/day.

LOAEL = could not be determined.

Offspring NOAEL = 180 (males), 212 (females) 

mg/kg/day.

LOAEL = could not be determined.

870.4100 Chronic (1 year) –

Dog (diet)

00161273 (1986)

Acceptable/guideline

ppm = 0, 50, 750 & 

7500

mg/kg/day (M&F) = 0, 

1.25, 18.75 & 187.5

NOAEL = 18.75 (males & females) mg/kg/day.

LOAEL = 187.5 (males & females) mg/kg/day, 

based on increased liver weights in males, and 

increased relative thyroid/parathyroid weights in 

females, with decreased body weight and body 

weight gain in females after week 22.

870.4200 Carcinogenicity 

(18-Month) –

Mouse (diet)

00161275 (1985)

40340321 (1987)

(individual pathology 

sheets)

Acceptable/guideline

ppm = 0, 25, 750 & 

7500

mg/kg/day (M/F) = 0/0, 

3.2/4.3, 97/128 & 

979/1312

NOAEL = 979 (males), 4.3 (females) mg/kg/day.

LOAEL = could not be determined (males), 128 

(females) mg/kg/day, based on a decrease in 

terminal body weights in the mid and high doses.

No evidence of carcinogenicity.

870.4300 Chronic/

Carcinogenicity 

(2-Year) –Rat 

(diet) 

00161274 (1986)

Acceptable/guideline

40340324 (1987)

Supplement

40340323 (1987) 

Supplement

ppm = 0, 25, 500 & 

2500

mg/kg/day (M/F) = 0/0, 

0.96/1.3, 20/26 & 

120/133

NOAEL = 20 (males), 26 (females) mg/kg/day.

LOAEL = 120 (males), 133 (females) mg/kg/day, 

based on decreased body weight and body weight 

gain.

No evidence of carcinogenicity.

870.5100

870.5265

Gene Mutation in 

S. typhimurium

and E. coli

00143662 (1984)

Acceptable/guideline

No mutagenic response ± S9 activation in TA 1535, 

97, 98 & 100. Cytotoxicity seen at HDT.

870.5300 Gene Mutation in 

CHO Mammalian 

Cells at HGPRT 

Locus

00145161 (1987)

40340325 (1987)

Acceptable/guideline

No mutations at HDT (7mM), which was above 

limit of solubility.

870.5375 CHO Cell 

Cytogenetics

44710403 (1996)

Acceptable/guideline

No evidence of chromosomal aberrations when 

tested up to cytotoxic or solubility limit 

concentrations.

870.5395 In vivo Rat Bone 

Marrow 

Micronucleus

00145560 (1984)

Acceptable/guideline

Negative for clastogenic response at 5000 mg/kg.
Page 28 of 37

TABLE A.2.2 Subchronic, Chronic and Other Toxicity Profile for Thifensulfuron Methyl. 

Guideline

Number

Study Title MRID Number Results

870.5550 Unscheduled 

DNA Synthesis in 

Primary 

Mammalian Cells

00143663 (1985)

Acceptable/guideline

No significant increase in UDS.

870.6200a Acute 

Neurotoxicity 

Screening Battery 

– Rat (gavage)

48817901 (2012)

0, 200, 700, or 2000 

mg/kg/day

NOAEL = 2000 mg/kg/day (limit dose). LOAEL 

not determined. 

870.6200b Subchronic 

Neurotoxicity 

Study – Rat (diet)

48817902 (2012)

ppm = 0, 750, 2500, & 

7500

mg/kg/day (M/F) = 0/0, 

42/46, 136/158, or 

421/489

NOAEL = 421 mg/kg/day (the HDT). LOAEL not 

determined.

870.7485 Metabolism Study 

– Rat

(gavage)

00161281 (1986)

Acceptable/guideline

low dose = 20 mg/kg

high dose = 2000 

mg/kg

Most of the radioactivity was recovered in the urine 

and feces (parent with 5 metabolites) with parent 

accounting for 55 and 72% for males and females, 

respectively. Minor metabolites included DPXM6316 acid (2.3-2.4%), O-demethyl DPX-M6316 

(0.4-0.5%), triazine amine (0.5%) and lesser 

amounts of 2-ester-e-sulfonamide and thiophene 

sulfonamide. Fecal metabolite profile was similar to 

that in urine. Unchanged DPX-M6316 acid is the 

primary excretory product (18 or 12% in males and 

females, respectively). Three metabolites remained 

unidentified.

870.7600 Dermal 

Absorption – Rats

No study has been submitted.

870.7800 Immunotoxicity 

Study – Rat (diet)

48686101 (2011)

Acceptable/guideline

Females only

ppm = 0, 250, 750, 

2500, 7000

mg/kg/day = 0, 19, 55, 

192, 529

Systemic Effects

NOAEL = 529 mg/kg/day

LOAEL = not attained (no clinical signs of toxicity)

Immunotoxicity Effects

NOAEL = 529 mg/kg/day

LOAEL = not attained (no immunotoxic effects)
Page 29 of 37

Appendix B. Review of Human Research

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

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

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

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

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

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.
Page 30 of 37

Appendix C. Occupational Algorithms

Occupational Non-cancer Handler Algorithms

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

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

where:

E = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),

AR = maximum application rate according to registered labels (lb ai/A), and

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

The daily doses are calculated using the following formula:

ADD= 

E * AF

BW

where:

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

E = exposure (mg ai/day),

AF = absorption factor (dermal or inhalation), and

BW = body weight (kg).

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

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

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

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

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

MOE= 

POD

ADD

where:

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

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

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).
Page 31 of 37

Occupational Non-cancer Post-application Algorithms

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

following formulas:

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

ug

lb) * (2.47E-8

A

cm2

)

where:

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

AR = application rate (lb ai/acre),

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

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

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

E=TC * DFR t* ET * 0.001

mg

ug

where:

E = exposure (mg ai/day),

TC = transfer coefficient (cm2/hr),

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

ET = exposure time (hours/day).

The daily doses are calculated using the following formula:

ADD= 

E * AF

BW

where:

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

E = exposure (mg ai/day),

AF = absorption factor (dermal), and

BW = body weight (kg).

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

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

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

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

MOE values are calculated using the following formula:

MOE= 

POD

ADD
Page 32 of 37

where:

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

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

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).
Page 33 of 37

Appendix D. Dietary Exposure/Risk Modeling Input and Output

US EPA Ver. 3.18, 03-08-d

DEEM-FCID Acute analysis for THIFENSULFURON METHYL

Residue file name: Thifensulfuron methyl.R08

Analysis Date 07-29-2015 Residue file dated: 07-29-2015/08:18:22

Reference dose (aRfD) = 1.59 mg/kg bw/day

Comment: Acute for females 13-49 only

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

 EPA Crop Def Res Adj.Factors Comment

 Code Grp Food Name (ppm) #1 #2 

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

1500025000 15 Barley, pearled barley 0.050000 1.000 1.000

1500025001 15 Barley, pearled barley-babyfood 0.050000 1.000 1.000

1500026000 15 Barley, flour 0.050000 1.000 1.000

1500026001 15 Barley, flour-babyfood 0.050000 1.000 1.000

1500027000 15 Barley, bran 0.050000 1.000 1.000

0101100000 1AB Chicory, roots 0.010000 1.000 1.000

0200101000 2 Chicory, tops 0.010000 1.000 1.000

1500120000 15 Corn, field, flour 0.050000 1.000 1.000

1500120001 15 Corn, field, flour-babyfood 0.050000 1.000 1.000

1500121000 15 Corn, field, meal 0.050000 1.000 1.000

1500121001 15 Corn, field, meal-babyfood 0.050000 1.000 1.000

1500122000 15 Corn, field, bran 0.050000 1.000 1.000

1500123000 15 Corn, field, starch 0.050000 1.000 1.000

1500123001 15 Corn, field, starch-babyfood 0.050000 1.000 1.000

1500124000 15 Corn, field, syrup 0.050000 1.000 1.000

1500124001 15 Corn, field, syrup-babyfood 0.050000 1.000 1.000

1500125000 15 Corn, field, oil 0.050000 1.000 1.000

1500125001 15 Corn, field, oil-babyfood 0.050000 1.000 1.000

2003128000 20C Cottonseed, oil 0.020000 1.000 1.000

2003128001 20C Cottonseed, oil-babyfood 0.020000 1.000 1.000

2001163000 20A Flax seed, oil 0.020000 1.000 1.000

1500231000 15 Oat, bran 0.050000 1.000 1.000

1500232000 15 Oat, flour 0.050000 1.000 1.000

1500232001 15 Oat, flour-babyfood 0.050000 1.000 1.000

1500233000 15 Oat, groats/rolled oats 0.050000 1.000 1.000

1500233001 15 Oat, groats/rolled oats-babyfood 0.050000 1.000 1.000

2001319000 20A Rapeseed, oil 0.020000 1.000 1.000

2001319001 20A Rapeseed, oil-babyfood 0.020000 1.000 1.000

1500323000 15 Rice, white 0.050000 1.000 1.000

1500323001 15 Rice, white-babyfood 0.050000 1.000 1.000

1500324000 15 Rice, brown 0.050000 1.000 1.000

1500324001 15 Rice, brown-babyfood 0.050000 1.000 1.000

1500325000 15 Rice, flour 0.050000 1.000 1.000

1500325001 15 Rice, flour-babyfood 0.050000 1.000 1.000

1500326000 15 Rice, bran 0.050000 1.000 1.000

1500326001 15 Rice, bran-babyfood 0.050000 1.000 1.000

2002330000 20B Safflower, oil 0.050000 1.000 1.000

2002330001 20B Safflower, oil-babyfood 0.050000 1.000 1.000

1500344000 15 Sorghum, grain 0.050000 1.000 1.000

1500345000 15 Sorghum, syrup 0.050000 1.000 1.000

0600347000 6 Soybean, seed 0.100000 1.000 1.000

0603348000 6C Soybean, flour 0.100000 1.000 1.000

0603348001 6C Soybean, flour-babyfood 0.100000 1.000 1.000

0600349000 6 Soybean, soy milk 0.100000 1.000 1.000

0600349001 6 Soybean, soy milk-babyfood or in 0.100000 1.000 1.000

0600350000 6 Soybean, oil 0.100000 1.000 1.000

0600350001 6 Soybean, oil-babyfood 0.100000 1.000 1.000

1500381000 15 Triticale, flour 0.050000 1.000 1.000

1500381001 15 Triticale, flour-babyfood 0.050000 1.000 1.000

8601000000 86A Water, direct, all sources 0.751000 1.000 0.655 Fact. 2=492/751 

(chronic/acute)

8602000000 86B Water, indirect, all sources 0.751000 1.000 0.655 Fact. 2=492/751 

(chronic/acute)

1500401000 15 Wheat, grain 0.050000 1.000 1.000

1500401001 15 Wheat, grain-babyfood 0.050000 1.000 1.000

1500402000 15 Wheat, flour 0.050000 1.000 1.000

1500402001 15 Wheat, flour-babyfood 0.050000 1.000 1.000

1500403000 15 Wheat, germ 0.050000 1.000 1.000
Page 34 of 37

1500404000 15 Wheat, bran 0.050000 1.000 1.000

US EPA Ver. 3.18, 03-08-d

DEEM-FCID ACUTE Analysis for THIFENSULFURON METHYL NHANES 2003-2008 2-Day

Residue file: Thifensulfuron methyl.R08 Adjustment factor #2 NOT used.

Analysis Date: 07-29-2015/08:19:38 Residue file dated: 07-29-2015/08:18:22

RAC/FF intake summed over 24 hours

Run Comment: "Acute for females 13-49 only"

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

Summary calculations--per capita:

 95th Percentile 99th Percentile 99.9th Percentile

Exposure % aRfD Exposure % aRfD Exposure % aRfD 

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

Female 13-49:

 0.041152 2.59 0.060229 3.79 0.085186 5.36 

US EPA Ver. 3.16, 03-08-d

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

Residue file name: Thifensulfuron methyl.R08

 Adjustment factor #2 used.

Analysis Date 07-29-2015/08:21:58 Residue file dated: 07-29-2015/08:18:22

Reference dose (RfD, Chronic) = .043 mg/kg bw/day

COMMENT 1: Acute for females 13-49 only

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

 Total exposure by population subgroup

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

 Total Exposure

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

 Population mg/kg Percent of 

 Subgroup body wt/day Rfd 

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

Total US Population 0.010530 24.5%

Hispanic 0.010092 23.5%

Non-Hisp-White 0.010816 25.2%

Non-Hisp-Black 0.008725 20.3%

Non-Hisp-Other 0.012139 28.2%

Nursing Infants 0.009502 22.1%

Non-Nursing Infants 0.034765 80.8%

Female 13+ PREG 0.009896 23.0%

Children 1-6 0.013737 31.9%

Children 7-12 0.008938 20.8%

Male 13-19 0.007336 17.1%

Female 13-19/NP 0.008148 18.9%

Male 20+ 0.009791 22.8%

Female 20+/NP 0.010976 25.5%

Seniors 55+ 0.010099 23.5%

All Infants 0.026965 62.7%

Female 13-50 0.010430 24.3%

Children 1-2 0.015430 35.9%

Children 3-5 0.013053 30.4%

Children 6-12 0.009403 21.9%

Youth 13-19 0.007745 18.0%

Adults 20-49 0.010473 24.4%

Adults 50-99 0.010305 24.0%

Female 13-49 0.010420 24.2%

-------------------------------------------------------------------------------
Page 35 of 37

Appendix E. Nomenclature and Physical/Chemical Properties

TABLE E.1 Thifensulfuron Methyl Nomenclature

Chemical structure

Common name Thifensulfuron methyl

Molecular formula C12H13N5O6S2

Molecular weight 387.38

Company experimental name DPX-M6316

IUPAC name Methyl 3-(4-methoxy-6-methyl-1,3,5-triazin-2-ylcarbamoylsulfamoyl) thiophene2-carboxylate

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

sulfonyl]-2-thiophenecarboxylate

CAS registry number 79277-27-3

TABLE E.2 Physicochemical Properties of the Technical Grade Thifensulfuron Methyl 

Parameter Value Reference

Melting point/range (oC) 171.1 ± 1.2 MRID #47138301 (D342084; 

D. Dotson; 17 April 2008)

pH 4.0

Density (g/cm3) 1.58 ± 0.004 

Water solubility (g/L at 25oC) pH 5 0.223

pH 7 2.24

pH 9 8.83

Solvent solubility (g/L at 25oC) Acetone - 11.9

Acetonitrile - 7.3

Dichloromethane - 27.5

Ethanol - 0.9

Ethyl acetate - 2.6

Hexane - <0.1 

Methanol - 2.6 

Xylene - 0.2

Vapor pressure (25oC) 1.7 x 10-8 Pa (1.3 x 10-10 mm Hg)

Dissociation constant (pKa) 4.0

Octanol/water partition coefficient

(Log [KOW])

pH 5 1.06 

pH 7 0.0222

pH 9 0.0078 

N

N

N

CH3

O

CH3

N

H

N

H

O

S

CO2CH3

S

O

O
Page 36 of 37

Appendix F. Spray Drift Detailed Description

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

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

deposit on surfaces where individuals come into contact with residues on these surfaces, leading

to indirect exposures (e.g., children playing on lawns where residues have deposited next to 

treated fields).

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

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them11. [Direct exposures would include inhalation of the spray plume or being sprayed 

directly.] Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

Given this premise, exposures for children (1 to 2 years old) and adults who have contact with 

turf where residues are assumed to have deposited via spray drift thus resulting in an indirect 

exposure are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment. 

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

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

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

address drift from the agricultural applications of thifensulfuron methyl. In the spray drift 

scenario, the deposited residue value was determined based on the amount of spray drift that may 

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

the Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration 

of Spray Drift Policy. Once the deposited residue values were determined, the remainder of the 

spray drift assessment was based on the algorithms and input values specified in the 2012 

Standard Operating Procedures for Residential Risk Assessment (SOPs). 

A screening approach was developed based on the use of the AgDrift model in situations where 

specific label guidance that defines application parameters is not available1213. AgDrift is 

appropriate for use only when applications are made by aircraft, airblast orchard sprayers, and 

groundboom sprayers. When AgDrift was developed, a series of screening values (i.e., the Tier 1 

option) were incorporated into the model and represent each equipment type and use under 

varied conditions. The screening options specifically recommended in this methodology were 

selected because they are plausible and represent a reasonable upper bound level of drift for 

common application methods in agriculture. These screening options are consistent with how 

spray drift is considered in a number of ecological risk assessments and in the process used to 

develop drinking water concentrations used for risk assessment. In all cases, each scenario is to 

be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are 

 

11 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.

12 http://www.agdrift.com/

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

assessors should be aware and characterize these appropriately.
Page 37 of 37

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

not allowed). Section 6.1.1 provides the screening level drift related risk estimates. 

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

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

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

estimates represent plausible options for pesticide labels.