UNITED STATES ENVIRO MENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF 

CH EM ICAL SAFETY AND 

POLLUT ION PREVENTION 

MEMORANDUM 

Date: September 15, 2015 

SUBJECT: Tritlusulfuron-Methyl: Human Health Risk Assessment in Support of 

Registration Review. 

PC Code: I 29002 

Decision No.: 503362 

DP Barcode: D426786 

Section 3 Registration Nos.: 352-569; 

352-583 

Petition No.: NA Regulatory Action: Registration Review 

Risk Assessment Type: Single Chemical Case No.: 7236 

Aggregate 

TXRNo.: NA CAS No.: 126535-15-7 

MRID No.: NA 40 CFR: 180.492 

FROM: 

THROUGH: 

TO: 

Jessica 

Abdallah 

Kidwell

Khasawinah. 

, Risk Assessor 

Ph.D., T4:c~~~gist. (L, ili11 tt.... ~.e,,l // C< ~ 

I van Nieves. Occupational/Residential Exposure Assessor 

Thurston Morton, Chemist and Dietary Exposure Assess ) 

Risk Assessment Branch IV 

Health Effects Division (7509P) 

Risk 

Charl

Assessment 

es Smith, Acting 

Branch 

Branch 

IV 

Chief C ~ 

Health Effects Division (7509P) 

Matthew Manupella, Chemical Review Manager 

Kevin Costello, Branch Chief 

Risk Management and Implementation Branch 2 (RMIB 2) 

Pesticide Re-Evaluation Division (7508P) 

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

that HED evaluate the hazard and exposure data and conduct dietary, occupational and 

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

from the currentl y registered uses of pesticides. This memorandum serves as IIED's draft human 

health risk assessment of the dietary, occupational, and non-occupational exposure, and 

aggregate risk from the registered uses of tri flusulfuron-mcthyl. 

Page l of 32 
Since the last human health risk assessment and scoping document. the fo llowing updates have 

been inc01poratedjor trijlusulfuron-methyl. 

1) The immunoloxicity and inhalation toxicity study requirements have been waived. 

2) An endpoint and point of departure have been selected.from the 90-day oral toxicity study 

in the rat to be used for the short-term incidental oral endpoint to assess spray driji 

exposure/risk estimates. 

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

./) A high-end screening drinking water exposure value was used to assess screening-level 

dietary exposure/risk estimates. 

Page 2 of 32 
Page 3 of 32

Table of Contents

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

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

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

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

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

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

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

4.0 Hazard Identification/Toxicology..................................................................................... 8

4.1 Summary of Toxicological Effects....................................................................................... 8

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) ............................................. 9

4.3 Toxicity Endpoint and Point of Departure Selections .......................................................... 9

4.4 Endocrine Disruptor Screening Program ....................................................................... 11

5.0 Dietary Exposure and Risk Assessment......................................................................... 12

5.1 Water Residue Profile .................................................................................................... 12

5.2 Food Residue Profile...................................................................................................... 12

5.3 Dietary Exposure and Risk Estimates............................................................................ 12

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 13

6.1 Spray Drift...................................................................................................................... 13

6.1.1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications.............. 13

6.2 Residential Bystander Post-Application Inhalation Exposure ....................................... 14

7.0 Aggregate Exposure/Risk Characterization.................................................................. 14

8.0 Cumulative Exposure/Risk Characterization ............................................................... 14

9.0 Occupational Exposure/Risk Characterization ............................................................ 15

9.1 Occupational Handler Exposure/Risk Estimates............................................................ 15

9.2 Occupational Post-application Exposure/Risk Estimates................................................... 17

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates........................... 17

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates............................... 17

10.0 Public Health and Pesticide Epidemiology Data........................................................... 18

11.0 Literature References...................................................................................................... 18

12.0 References......................................................................................................................... 18

Appendix A. Toxicology Data Requirements and Toxicology Profile ................................... 19

Appendix B. Review of Human Research................................................................................ 25

Appendix C. Occupational Non-cancer Handler Algorithms.............................................. 26

Appendix D. Dietary Exposure/Risk Modeling Input and Output ..................................... 27

Appendix E. Nomenclature and Physical/Chemical Properties............................................. 28

Appendix F. Spray Drift Detailed Description......................................................................... 30

Appendix G. Analytical Standards Status................................................................................ 32
Page 4 of 32

1.0 Executive Summary

Triflusulfuron-methyl is a sulfonylurea herbicide that inhibits the biosynthesis of branched-chain 

amino acids in plants (via inhibition of the plant enzyme acetolactate synthase). Marketed as 

UpBeet®, a dry flowable (DF) formulation containing 50% active ingredient (ai), triflusulfuronmethyl is currently approved for use on sugar beet, garden beet, and chicory/Belgium endive for 

selective postemergence control, or partial control, of broadleaf and grass weeds. It is applied via 

broadcast (ground- or aerial-based) or band application methods at seasonal rates of up to 0.078 

pounds ai per acre (lb ai/A) for sugar beets and 0.047 lb ai/A for garden beets/chicory/Belgium 

endive. UpBeet® is not to be applied via any type of irrigation system. The existing label for 

UpBeet® lists a pre-harvest interval (PHI) of 60 days for both sugar beet and chicory and 30 days 

for garden beets. 

The most recent risk assessment for triflusulfuron-methyl was conducted in 2011 (E. Holman et 

al., D388621, 4/13/2011). A human health scoping document was conducted in 2012 (S. Recore, 

D399195, 5/3/2012). Immunotoxicity and inhalation toxicity studies were identified as data gaps,

however, the immunotoxicity study requirement has since been waived for the entire class of 

sulfonylurea chemicals (K. Rury, TXR# 0056723, 8/6/2013). Additionally, HED’s Hazard and 

Science Policy Council (HASPOC) has waived the inhalation toxicity study requirement (J. Van 

Alstine, TXR# 0056291, 6/7/2012). 

The toxicology database for triflusulfuron is considered complete and adequate for risk 

assessment. The existing tolerances (40 CFR 180.492) are supported by adequate residue 

chemistry data. For this assessment, the toxicological endpoints and points of departure (PODs) 

have been updated to include an incidental oral risk assessment in order to assess exposure from 

spray drift; dermal risks are not anticipated. All other endpoints/PODs selected for risk 

assessment remain the same as in the previous assessments. This draft risk assessment 

incorporates all new data and includes updates to hazard and exposure assessments, science 

policies, and procedures. 

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

triflusulfuron-methyl using tolerance-level residues in foods and a sulfonylurea-class-wide 

screening-level estimate of residues in drinking water. Dietary risk estimates range from 1.3 to 

4.5% of the chronic population adjusted dose (cPAD) and are below HED’s level of concern

(LOC). HED did not conduct an acute dietary exposure/risk assessment due to the lack of an 

appropriate endpoint for acute dietary assessment.

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

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

performed. However, triflusulfuron-methyl can be applied via groundboom and aerial equipment 

and, therefore, there is the potential for indirect exposure to triflusulfuron-methyl via spray drift.

As a result, incidental oral risk estimates for children 1 to <2 years old were calculated. No risks 

of concern were identified at the edge of the field in the spray drift assessment. 

In the case of triflusulfuron-methyl, aggregate exposure and risk estimates are equivalent to the 

dietary exposure and risk estimates and do not exceed HED’s level of concern.
Page 5 of 32

No chemical-specific data were submitted in support of this draft risk assessment; therefore, 

HED relied on the best available data to assess occupational handler and post-application

exposure. Default assumptions established by HED’s Science Advisory Council for Exposure 

(ExpoSAC) were used for parameters such as body weight and amount handled. Since dermal 

risks are not anticipated due to the absence of dermal toxicity/endpoint, the occupational handler 

assessment is based on inhalation exposures only and a dermal occupational post-application 

assessment was not conducted. All occupational handler scenarios for the registered uses resulted 

in MOEs greater than the level of concern (LOC) of 100 at baseline level of risk mitigation (i.e., 

baseline attire with no gloves or respirator). The lowest MOE of 1500 is associated with 

mixing/loading a dry flowable formulation applied aerially up to 1,200 acres. All other MOEs 

were significantly higher, ranging from 9200 to 2,800,000. No additional personal protective 

equipment (PPE) recommendations are needed on the registered labels. 

 

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

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

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for triflusulfuron-methyl. 

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

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

HED has not identified any risk concerns associated with the registered uses of triflusulfuronmethyl. 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 existing tolerances (40 CFR 180.492) are supported by the available residue chemistry data. 

At this time, there are no Codex or Canadian MRLs; therefore, international harmonization is not 

a consideration for triflusulfuron-methyl during registration review. 

The tolerance expression for triflusulfuron-methyl cited in 40CFR §180.492[a] is correct 

according to HED’s Interim Guidance on Tolerance Expressions (S. Knizner, 27 May 2009), and 

is as follows: 

Tolerances are established for residues of triflusulfuron-methyl, including its 

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

Compliance with the tolerance levels specified below is to be determined by 

measuring only triflusulfuron-methyl (methyl 2-[[[[[4-(dimethylamino)-6-(2,2,2-

trifluoroethoxy)-1,3,5-triazin-2-yl]amino]carbonyl]amino]sulfonyl]-3-

methylbenzoate) in or on the commodity. 
Page 6 of 32

3.0 Introduction

3.1 Chemical Identity and Physical/Chemical Characteristics

Triflusulfuron-methyl has a molecular weight of 492 Daltons and a melting point of 155 - 158C. 

The water solubility of triflusulfuron-methyl is highly pH dependent. At pH 5, the solubility is 

2.7 ppm, whereas at pH 9 the solubility increases to 11,000 ppm. This herbicide has a vapor 

pressure of less than 110-7 mm Hg. Exposure to triflusulfuron-methyl via volatilization is 

extremely unlikely.

Triflusulfuron-methyl is a non-persistent compound. While its low adsorption coefficients and 

high water solubility at environmental pHs indicate that triflusulfuron-methyl may leach to 

groundwater, its short half-life suggests that it will not accumulate from repeated applications in 

either surface or ground water. The nomenclature and physical/chemical properties of 

triflusulfuron-methyl are provided in Appendix E.

3.2 Pesticide Use Pattern and Anticipated Exposure Pathways

Triflusulfuron-methyl is marketed as UpBeet, a dry flowable (DF) formulation containing 50% 

active ingredient (ai), triflusulfuron-methyl is currently approved for use on sugar beet, garden 

beet, and chicory/Belgium endive using broadcast (ground- or aerial-based) or band application 

methods at seasonal rates of up to 0.078 pounds ai per acre (lb ai/A) for sugar beets and 0.047 lb 

ai/A for garden beets/chicory/Belgium endive. UpBeet is not to be applied via any type of 

irrigation system (Table 3.2). The existing label for UpBeet lists a pre-harvest interval (PHI) of 

60 days for both sugar beet and chicory and 30 days for garden beets. 

Based on the use pattern which allows only one application per season, the duration of exposure

for occupational handlers in conjunction with the registered uses 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, chemical-resistant gloves and protective eyewear. The restricted entry interval (REI) on 

all labels is 4 hours.

Exposure Pathways

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

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

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

triflusulfuron-methyl related to spray drift. Agricultural workers may be exposed (inhalation) to 

triflusulfuron-methyl during mixing, loading, and/or applying the herbicide as well as during 

post-application activities. 
Page 7 of 32

TABLE 3.2. Summary of Directions for Use of Triflusulfuron-Methyl

Trade 

Name

Application 

Timing

Application 

Rate 

(lb ai/A)

Max. 

No. 

Applic. 

per 

Season

RTI1

(days)

Max. 

Seasonal 

Applic. 

Rate

(lb ai/A)

PHI2

(days)

Use Directions and other 

Limitations

(i.e. grazing, type of 

application/equipment, 

plant-back interval, other)

Garden Beets

UpBeet® 

Herbicide

EPA Reg 

# 352-569

Apply as a postemergent spray 

when garden 

beets are at the 

following 

stages: 2-4 leaf 

stage; 4-6 leaf 

stage; and 6-8 

leaf stage.

0.016 3 See 

application 

timing

0.047 30 Ground or aerial application 

equipment. 

Do not apply through any 

type of irrigation 

equipment.

Sugar Beets

UpBeet® 

Herbicide

EPA Reg 

# 352-569

Postemergence Broadcast 0.032

Banded 0.016

NS 5-10 0.078 60 Ground or aerial

Do not apply through any 

type of irrigation 

equipment.

Chicory/Belgium Endive

UpBeet® 

Herbicide

EPA Reg 

# 352-569

Postemergence 

when at least 1 

true leaf has 

developed

0.016 NS 5-10 0.047 60 Ground or aerial

Do not apply through any 

type of irrigation 

equipment.

1 RTI = retreatment interval

2PHI = Pre-Harvest Interval
Page 8 of 32

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://www.eh.doe.gov/oepa/guidance/justice/eo12898.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 Continuing 

Survey of Food Intake by Individuals (CSFII) 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, season of the year, ethnic group, and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

exposures based on home use of pesticide products and associated risks for adult applicators and 

for toddlers, youths, and adults entering or playing on treated areas post-application are 

evaluated. Further considerations are currently in development as OPP has committed resources 

and expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

4.0 Hazard Identification/Toxicology

The toxicology database for triflusulfuron-methyl is complete and adequate for risk 

assessment. Immunotoxicity and inhalation studies are not available for triflusulfuron-methyl, as

required in accordance with the current 40 CFR Part 158 Toxicology Data Requirements. 

However, the Hazard and Science Policy Council (HASPOC) determined that these studies are 

not required at this time for triflusulfuron-methyl (TXR 0056291 and TXR 0056723). The most 

recent risk assessment was conducted in 2011 (Elizabeth Holman, D388621, 4/13/2011). No new 

toxicity and/or metabolism data have been received and the endpoints selected for the previous 

risk assessment remain the same, with the exception of a short-term incidental oral endpoint 

which was selected for the spray drift assessment. For a summary of the acute, subchronic and 

chronic toxicity profile, see Appendix A.

4.1 Summary of Toxicological Effects

The primary target organs identified for triflusulfuron-methyl are the liver, testes and red blood 

cells. Hematological and histopathological changes consistent with mild hemolytic anemia were 

observed in the rat and the dog. Increased incidence of testicular interstitial hyperplasia was 

observed following subchronic or chronic-term dietary administration to the rat; the incidence of 

testicular interstitial adenomas was also increased with chronic exposure. In the dog, testicular 

atrophy and reduced size were observed following subchronic or chronic exposure. Liver effects 

were observed in the dog (increased weight, altered serum enzyme profile and histopathology) 
Page 9 of 32

and mouse (increased weight and histopathology), but not in the rat. There was no indication of

frank neurotoxicity in the available studies. The only potential evidence of immunotoxicity 

observed for triflusulfuron-methyl was hemolytic anemia, an effect that is associated with 

exposure to some sulfonylurea compounds as an immune-mediated cytotoxicity. However, there 

are currently no data demonstrating that hemolytic anemia from triflusulfuron-methyl is 

immune-mediated. 

No effects of treatment were reported in a 21-day repeated application dermal toxicity study in 

the rabbit. Dermal absorption studies were not submitted.

There was no quantitative or qualitative evidence of increased pre- and/or postnatal susceptibility 

in rat or rabbit developmental toxicity studies or in the rat reproductive studies. No 

developmental effects were seen in the rat developmental study, whereas maternal toxicity 

(decreased body weight gain, food consumption and feed efficiency) was observed at the highest 

two doses. Abortions were observed in the rabbit developmental toxicity study at a dose that also 

caused significant maternal toxicity, including mortality, clinical signs, sharply reduced food 

consumption and decreased weight gain. In the rat reproductive toxicity study, decreased 

parental body weight/weight gain and F1 pup weight during lactation were observed at the mid 

and high doses. No reproductive effects were observed.

In acute lethality studies, triflusulfuron-methyl has low acute toxicity when administered orally 

(Toxicity Category IV), dermally (Category III), or via inhalation (Category IV). It is not a 

dermal sensitizer or irritant (Category IV) and causes only minor transient irritation to the eye 

(Category III).

Triflusulfuron-methyl was classified as a “Group C” (possible human) carcinogen under the 

1986 Agency Guidelines for Carcinogen Assessment (TXR No. 0011939). The classification was 

based on an increased incidence of testicular interstitial cell adenomas in male rats and evidence 

of clastogenicity in some in vitro genotoxicity studies. Quantification of cancer risk using a nonlinear approach (i.e., RfD) was recommended to adequately account for all chronic toxicity, 

including carcinogenicity, that could result from exposure to triflusulfuron-methyl.

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

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

(SF) be reduced to 1x for triflusulfuron-methyl. The toxicity database of triflusulfuron-methyl is 

complete and adequate to assess potential susceptibility in the young. There is no evidence of 

increased qualitative or quantitative susceptibility in the young, there is no concern for

neurotoxicity, and exposure estimates are unlikely to underestimate risk; therefore, the FQPA 

Safety Factor is reduced to 1X. 

4.3 Toxicity Endpoint and Point of Departure Selections

There have been no changes to the prior endpoints/PODs selected for risk assessment and cancer 

classification, with the exception of a short-term incidental oral endpoint that was selected to 

assess spray drift for registration review. It should be noted that the endpoints and points of 

departure (POD) presented in the Table 4.3.1 have not been updated to comply with current 
Page 10 of 32

policy. The NOAELs and LOAELS have not been changed. Therefore, the endpoints/PODs 

selected for risk assessment may be conservative. 

Table 4.3.1. Summary of Toxicological Doses and Endpoints for Triflusulfuron-Methyl for Use in Dietary, 

Occupational and Non-Occupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary, 

General 

Population 

(including 

Infants and 

Children and 

Females age 13 

to 49)

Not required. An appropriate endpoint for this risk assessment was not identified.

Chronic 

Dietary (All 

Populations)

NOAEL= 

2.44 

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x 

Chronic RfD = 

0.0244

mg/kg/day

cPAD = 0.0244 

mg/kg/day

Chronic oral toxicity/carcinogenicity in 

the rat. MRID 42991413

LOAEL = 30.6 mg/kg/day, based on

decreased body weight/weight gain, 

hematological changes (primarily males) 

and increased interstitial cell hyperplasia 

(males).

Short-term 

Incidental Oral

NOAEL = 

6.56 

mg/kg/day

UFA=10x

UFH=10x LOC for MOE 

= 100

90-day oral toxicity in the rat

MRID 42991408

LOAEL = 133 mg/kg/day (males)/153 

mg/kg/day (females), based on decreased 

body weight gain (observed after the first 

week of dosing) and body weight, and in 

females, extra medullary hematopoiesis

Inhalation 

Short-Term (1 

to 30 days) and 

IntermediateTerm (1 to 6 

months)

NOAEL = 

6.56 

mg/kg/day

UFA=10x

UFH=10x

Occupational 

LOC for MOE 

= 100

90-day oral toxicity in the rat

MRID 42991408

LOAEL = 133 mg/kg/day (males)/153 

mg/kg/day (females), based on decreased 

body weight gain (observed after the first 

week of dosing) and body weight, and in 

females, extra medullary hematopoiesis.

Dermal all 

durations

Not required. No toxicity was observed in the rabbit 21-day dermal toxicity study up to the 

limit dose of 1000 mg/kg/day and there is no concern for susceptibility.

Cancer (oral, 

dermal, 

inhalation)

Classification: Group C (1986 Cancer Guidelines), based on increased incidence of testicular 

interstitial cell adenomas in rats. A non-linear approach (ie, RfD) is considered adequately 

protective of these effects and a quantitative assessment of cancer risk using a cancer potency 

factor is not required.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

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

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

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

sensitivity among members of the human population (intraspecies). RfD = Reference Dose. FQPA SF = FQPA 

Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). LOC = level of concern. MOE = margin of 

exposure
Page 11 of 32

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 triflusulfuron-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), triflusulfuron-methyl is subject to the endocrine screening part of the 

Endocrine Disruptor Screening Program (EDSP).

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

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

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

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

statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to 

identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid

(E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to 

have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of 

the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on 

the available data. Tier 2 testing is designed to identify any adverse endocrine-related effects 

caused by the substance, and establish a dose-response relationship between the dose and the E, 

A, or T effect.

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

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

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

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

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

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

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

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

website2.

 

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

chemicals.

2 http://www.epa.gov/endo/
Page 12 of 32

5.0 Dietary Exposure and Risk Assessment 

5.1 Water Residue Profile

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

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

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

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

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

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

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

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

provided by BEAD if the labels do not provide a maximum seasonal rate. The modeled sorption 

coefficient is also chemical-specific. All other inputs, including the screening assumptions of 

stability to degradation and application every year, remained the same as for the coarse 

screen. The resulting refined-screen EDWCs from PRZM-GW can be used as a conservative 

estimate of exposure and are summarized in Table 5.1 (G. Orrick, D427429, 8/12/2015).

The chronic dietary assessment for triflusulfuron-methyl used the refined-screen postbreakthrough mean value of 20 μg/L (0.02 ppm).

Table 5.1. PRZM-GW Refined-Screen EDWCs for Sulfonylureas

Sulfonylurea (Use) PRZM-GW 

Scenario Max. Daily Conc. (μg/L) Post-breakthrough Mean (μg/L)

Mean Breakthrough 

Time (years)

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

Halosulfuron-methyl (fallow) NC cotton 74 53 8.1

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

Prosulfuron (corn) NC cotton 15 13 12

Rimsulfuron (commercial 

areas)

NC cotton 105 71 6.5

Triasulfuron (rangeland) NC cotton 21 19 16

Tribenuron-methyl (corn) NC cotton 35 23 6.1

Triflusulfuron-methyl 

(sugarbeet)

FL citrus 23 20 9.5

5.2 Food Residue Profile 

Triflusulfuron-methyl is registered for use on garden beets, sugar beets, and chicory. Tolerances 

have been established for residues in garden beet roots (0.01 ppm), garden beet tops (0.02 ppm) 

sugar beet roots (0.05 ppm), sugar beet tops (0.05 ppm), and chicory roots (0.05 ppm). In 

conducting this assessment, HED has assumed tolerance-level residues in all commodities and 

that 100% was treated with triflusulfuron-methyl.

5.3 Dietary Exposure and Risk Estimates

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

the Food Commodity Intake Database (DEEM-FCID; version 3.18). The model uses food 
Page 13 of 32

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 triflusulfuron-methyl, the dietary risk estimates (Table 5.3) range from 1.3 to 4.5% 

of the cPAD and are below HED’s level of concern. Because of the very conservative 

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

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

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

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

an endpoint appropriate for acute dietary assessment.

Table 5.3. Summary of dietary exposure and risk estimates for Triflusulfuron-Methyl.

Chronic Estimates

Population Group Exposure,

mg/kg bw/day Risk, % cPAD

Total US Population 0.000433 1.8

All Infants (< 1 year old) 0.001091 4.5

Children 1-2 years old 0.000639 2.6

Children 3-5 years old 0.000549 2.2

Children 6-12 years old 0.000396 1.6

Youth 13-19 years old 0.000319 1.3

Adults 20-49 years old 0.000428 1.8

Adults 50-99 years old 0.000422 1.7

Female 13-49 years old 0.000427 1.8

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no registered residential uses associated with triflusulfuron-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. 

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-foot wide lawns coupled with 

methods employed for residential risk assessments for turf products. Triflusulfuron-methyl is 

used on sugar beets, garden beets, and chicory via groundboom and aerial equipment. 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. 
Page 14 of 32

• Aerial applications are based on the use of AgDrift Tier 1 aerial option for a fine-tomedium spray type and a series of other parameters which 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). 

Since dermal risks are not anticipated due to the absence of dermal toxicity, the spray drift 

assessment is based on incidental oral exposures only. The highest exposure resulted from drift 

following triflusulfuron applications using aerial equipment, for children 1 to <2 years old 

(margins of exposure (MOEs) ≥ 52,000, 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 treated with 

triflusulfuron via aerial or ground equipment). See Table 6.1.1 for detailed results.

Table 6.1.1. Children (1<2 years old) Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for 

Triflusulfuron-Methyl for the Incidental Oral Route of Exposure.

Crop/Rate 

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

(ug/cm2) At Edge of the Field

Aerial Fine to Medium 0.032 0.0036 52,000

Groundboom High Boom Very fine to Fine 72,000

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 

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

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

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

subsequent Volatilization Screening Analysis.3 During Registration Review, the agency will 

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

studies) or further analysis is required for triflusulfuron-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 triflusulfuron-methyl, aggregate exposure and risk 

estimates are equivalent to the dietary exposure and risk estimates in Section 5, above, and are 

below HED’s level 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 

 

3 Available at: http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219.
Page 15 of 32

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)[4and conducting cumulative risk assessments (CRA)[5. The Agency has utilized 

this framework to evaluate the Sulfonylureas (SUs) of which triflusulfuron-methyl is a member 

(J. D’Agostino; D428798; 9/9/15). Although the SUs share some chemical and toxicological 

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

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

evaluation is necessary. 

9.0 Occupational Exposure/Risk Characterization

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 use on sugar beet, garden beet, 

and chicory/Belgium endive. The quantitative exposure/risk assessment developed for 

occupational handlers is based on the scenarios listed in Table 9.1. Based on the use pattern (i.e., 

1 application per season) and resistance management practices, occupational exposure from the 

registered food use 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., than 6 months) are 

not anticipated.

Occupational Handler Exposure, Assumptions and Risk Estimate Equations

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 & Absorption Factor: The standard body weight (80 kg) was used in this risk 

assessment since the endpoint selected was not developmental and/or based on fetal effects. 

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.

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

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

include PHED 1.1, and the 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 

 

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

(USEPA, 1999)

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

(USEPA, 2002)
Page 16 of 32

exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate 

Reference Table6.” HED policy on use of surrogate data, including descriptions of the various 

sources, can be found at the Agency website7. 

Area Treated: The area treated inputs were based on the Science Advisory Council for Exposure 

Policy 9.1: Standard Values for Daily Acres Treated in Agriculture (listed in Table 9.1).

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

occupational handlers can be found in Appendix C.

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimate

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

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

control for aerial applications (i.e., enclosed cockpits) and, therefore, are not of concern. The 

lowest MOE of 1,500 is associated with mixing/loading a dry flowable formulation that is being 

applied aerially over up to 1,200 acres. All other MOEs were significantly higher, ranging from 

9,200 to 2,800,000. No additional PPE recommendations are needed on the registered labels. 

Table 9.1. Short-term Handler Exposure and Risk Estimates for Triflusulfuron-Methyl.

Exposure Scenario Mitigation Levela

Inhalation Unit 

Exposureb

(mg/lb ai)

Application 

Ratec

(lb ai/A)

Area Treatedd

Inhalation 

Dosee

(mg/kg/day)

Total MOEf

Mixer/Loader

Dry Flowable (WG) 

for Aerial Application

Baseline 0.00896 0.032

1,200 A/day 0.0043 1,500

Dry Flowable for 

Groundboom 

Application

200 A/day 0.00072 9,200

Applicator

Sprays for

Aerial Application

Engineering 

Controls 

(Enclosed 

Cockpit)

0.0049

0.032

1,200 A/day 2.4 x 10-6 2,800,000

Sprays for 

Groundboom 

Application

Baseline 0.00034 200 A/day 0.000027 240,000

Flagger

Flagging Sprays for 

Aerial Application Baseline 0.00035 0.032 350 A/day 0.000049 130,000

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” (i.e., aerial applications enclosed cockpit).

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

c. Based on maximum single application rates 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. Short-term Inhalation Dose (mg/kg/day) = [Rate (lb ai/A) x UE (mg /lb ai) x Acres Treated (A/day)]/BW (80 kg).

f. MOE = Short-term Inhalation NOAEL (6.56 mg/kg/day)/ Short-term Inhalation Dose (mg/kg/day). LOC=100.

 

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

7 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Page 17 of 32

9.2 Occupational Post-application Exposure/Risk Estimates

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 utilize this analysis to determine 

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

required for triflusulfuron-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

No post-application chemical-specific data were submitted in support of registration review. A 

short-term dermal post-application exposure assessment is not required due to the absence of 

systemic and dermal toxicity in the dermal toxicity study.

Restricted Entry Interval

The REI specified on the registered labels is based on the acute toxicity of triflusulfuron-methyl. 

Triflusulfuron-methyl is classified as Toxicity Category III by the dermal route, Toxicity 

Category IV for eye irritation potential, and Toxicity Category IV for skin irritation potential. 

Under the Worker Protection Standard for Agricultural Pesticides, active ingredients classified as 

acute toxicity categories III or IV for these routes are usually assigned a 12-hour REI. However, 

triflusulfuron-methyl meets the criteria in PR Notice 95-3 for low risk pesticides that are 

permitted to have a 4-hour REI. Therefore, HED has no objections to the 4-hour REIs on the 

existing registered label (for sugar beet and chicory uses) and the proposed supplemental label 

for garden beet. 
Page 18 of 32

10.0 Public Health and Pesticide Epidemiology Data

An updated HED incident report was conducted for triflusulfuron-methyl in 2012 (D399193, S. 

Recore, 5/03/2012). 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 Agency will 

continue to monitor the incident information.

11.0 Literature References

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

information that would impact the current risk assessment. 

12.0 References

Author DP 

Barcode

and/or 

TXR No.

Date Title

V. Dobozy 

and E. Rinde

TXR No. 

0011939

5/28/1996 Carcinogenicity Peer Review of Triflusulfuron-Methyl

E. Holman, M. 

Collantes, L. 

Hansen

D388621 4/13/2011 Triflusulfuron-Methyl: Revised Human Health Risk Assessment 

for Proposed Use in Garden Beet.

A. 

Khasawinah,

J. Kidwell,

T. Morton,

S. Hummel,

I. Nieves

D399195 5/8/2012 Triflusulfuron-Methyl: Human Health 

Risk Scoping Document in Support of Registration Review

S.Recore D399193 5/03/2012 Triflusulfuron-Methyl: Review of Human Incidents

K. Rury TXR No. 

0056723

8/6/2013 Sulfonylureas: Summary of Hazard and Science Policy Council (HASPOC) 

Meeting of July 18, 2013: Recommendations on Data Requirement for 

Immunotoxicity Studies for Sulfonylurea Pesticides.

J. Van Alstine TXR 

0056291

6/7/2012 Triflusulfuron-Methyl: Summary of Hazard and Science Policy 

Council (HASPOC) Meeting of April 12, 2012: Recommendations 

on the need for a 28-day inhalation study.

G. Orrick D427429 8/12/2015 Drinking Water Exposure Assessment for the Registration Review 

of 22 Sulfonylurea Herbicides
Page 19 of 32

Appendix A. Toxicology Data Requirements and Toxicology Profile 

A.1 Toxicology Data Requirements

The toxicology requirements (40 CFR 158.340) for the triflusulfuron-methyl food use are shown 

below. Use of the new guideline numbers does not imply that the new (1998) guideline protocols 

were used.

Test Triflusulfuron-methyl, Technical

Required Satisfied

870.1100 Acute Oral Toxicity

870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity

870.2400 Primary Eye Irritation

870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

870.3150 Oral Subchronic (non-rodent)

870.3200 21-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation

yes

yes

yes

no

waived1

yes

yes

yes

-

-

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

870.5550 Mutagenicity—Other Genotoxic Effects

yes

yes

yes

yes

yes

yes

yes

yes

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 Develop. Neurotoxicity

no

no

yes

yes

no

--

--

yes

yes

--

870.7485 General Metabolism

870.7600 Dermal Penetration

yes

no

yes

no

870.7800 Immunotoxicity yes waived2

1 The requirement for this study has been waived (TXR 0056291)

2 The requirement for this study has been waived (TXR 0056723)
Page 20 of 32

A.2 Toxicity Profiles

A.2.1 Acute Toxicity Profile – Triflusulfuron-methyl technical

Guideline 

No.

Study Type MRID(s) Results Toxicity 

Category

870.1100 Acute oral - rat 42496819 

(1992)

LD50 > 5000 mg/kg (both sexes) IV

870.1200 Acute dermal - rabbit 42496826 

(1991)

LD50 > 2000 mg/kg (both sexes) III

870.1200 Acute dermal - rat 42496825 

(1991)

LD50 > 2000 mg/kg (both sexes) III

870.1300 Acute inhalation - rat 42496828 

(1991)

LC50 > 5.1 mg/L (both sexes) IV

870.2400 Primary eye irritation - rabbit 42496830 

(1992)

Slight irritation of cornea and 

conjunctive clearing within 72 hrs.

III

870.2500 Primary dermal irritation - rabbit 42496834 

(1992)

Slight irritation clearing within 48 

hrs.

IV

870.2600 Skin sensitization - guinea pig 42496837 

(1992)

Not a sensitizer (Buehler method) N/A
Page 21 of 32

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Triflusulfuron-Methyl

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 90-Day oral 

toxicity (rat)

MRID 42991408 (1992)

Acceptable/guideline

0, 100, 2000, 10,000 or 

15,000 ppm

(0, 6.56, 133, 658 or 1036 

mg/kg/day in males;

0, 7.71, 153, 783 or 1124 

mg/kg/day in females)

NOAEL = 6.56/7.71 mg/kg/day in m/f 

LOAEL = 133/153 mg/kg/day in m/f, based on 

decreased body weight gain and food efficiency 

in males; increased incidence of extra 

medullary hematopoiesis in females. Mild 

regenerative anemia was observed at 10,000 

ppm. 

870.3100 90-Day oral 

toxicity (rat)

MRID 42991406 and -07 

(1990)

Acceptable/guideline

0, 100, 2000, 10,000 or 

15,000 ppm 

(males 0, 6.20, 127, 646 

or 965 mg/kg/day;

Females 0, 7.54, 150, 774 

or 1070 mg/kg/day)

NOAEL = 6.2/7.54 mg/kg/day in m/f

LOAEL = 127/150 mg/kg/day in m/f, based on 

decreased body weight and weight gain and 

food efficiency, mild regenerative anemia in 

males and hemosiderin in the renal proximal 

tubular epithelium of females. At 15,000 ppm, 

testicular tubular atrophy in males and renal 

tubular cell atrophy in females were observed.

870.3150 90-Day oral 

toxicity (dog)

MRID 42496840 (1991)

Acceptable/guideline

0, 100, 4000 or 8000 ppm 

in the diet

(males 0, 3.9, 146.9 or 

267.6 mg/kg/day;

females 0, 3.7, 159.9 or 

250.7 mg/kg/day) 

NOAEL = 3.9/3.7mg/kg/day in m/f 

LOAEL = 146.9/159.9 mg/kg/day in m/f, 

based on increased SGOT, SGPT and alkaline 

phosphatase, increased liver weight, decreased 

testes weight, and microscopic changes in the 

testes and liver. Decreased body weights and 

effects on hematologic parameters were seen at 

8000 ppm only.

870.3200 21-Day dermal 

toxicity (New 

Zealand white 

rabbit)

MRID 42991409 (1993)

Acceptable/guideline

0, 50, 350 or 1000 

mg/kg/day applied for 6 

hr/day, 21 days

NOAEL = 1000 mg/kg/day (HDT). 

LOAEL was not observed (>1000 mg/kg/day). 

870.3700a Prenatal 

developmental in 

Crl:CD(BR) rat

MRID 42496841 (1991)

Acceptable/guideline

0, 30, 120, 350 or 1000 

mg/kg/day by gavage

Maternal NOAEL = 120 mg/kg/day

Maternal LOAEL = 350 mg/kg bw/day, based 

on reduced body weight gain and lower food 

efficiency.

Developmental NOAEL = 1000 mg/kg /day

Developmental LOAEL was not observed 

>1000 mg/kg/day).

870.3700b Prenatal 

developmental in 

New Zealand white 

rabbit

MRID 42496842 (1991)

Acceptable/guideline

0, 15, 90, 270 or 800 

mg/kg/day by gavage

Maternal NOAEL = 90 mg/kg/day 

Maternal LOAEL = 270 mg/kg/day, based on 

maternal death and abortions, clinical signs and 

decreased weight gain. 

Developmental NOAEL = 90 mg/kg/day 

Developmental LOAEL = 270 mg/kg/day, 

based on increased abortions and decreased 

mean fetal body weight. 
Page 22 of 32

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Triflusulfuron-Methyl

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3800 Reproduction and 

fertility effects

(rat) 

MRID 42496843; 

42991412 (1993)

Acceptable/guideline

0, 10, 100, 750 or 1500 

ppm in the diet (males 0, 

0.588, 5.81, 44.0 or 89.5 

mg/kg/day; 

females 0, 0.764, 7.75, 

58.0 or 115 mg/kg/day)

Parental NOAEL = 5.81/7.75 mg/kg/day in 

m/f

Parental LOAEL = 44/58 mg/kg/day in m/f, 

based on decreased body weight/body weight 

gain. 

Offspring NOAEL = 5.81/7.75 mg/kg/day in 

m/f

Offspring LOAEL = 44/58 mg/kg/day in m/f, 

based on decreased F1 pup body weight during 

lactation.

Reproductive NOAEL = 89.5/115 mg/kg/day 

in m/f

Reproductive LOAEL = not determined 

(>89.5/115 mg/kg/day in m/f)

870.4100a Chronic toxicity

(rat) –

See 870.4300, MRID 42991413

870.4100b Chronic toxicity 

(dog)

MRID 42991410 (1993)

Acceptable/guideline

0, 35, 875 or 3500 ppm in 

the diet

(males 0, 1.0, 26.9 or 

111.6 mg/kg/day;

females 0, 1.2, 27.7 or 

95.5 mg/kg/day)

NOAEL = 26.9/27.7 mg/kg/day in m/f

LOAEL = 111.6/95.5 mg/kg/day in m/f, based 

on increased alkaline phosphatase (males), liver 

weight and incidence of minimal centrilobular 

hepatocellular hypertrophy. Marginal 

reductions in RBC parameters were also 

observed.

870.4200a Carcinogenicity

(rat) See 870.4300, below

870.4200b Carcinogenicity

(CD-1mouse)

MRID 42991411 (1993)

Acceptable/guideline

0, 150, 2500 or 7000 ppm 

in the diet 

(males 0, 1.37, 20.9, 349 

or 1024 mg/kg/day ;

females 0, 1.86, 27.7, 488 

or 1360 mg/kg/day)

NOAEL = 20.9/27.7 mg/kg/day in m/f

LOAEL = 349/488 mg/kg/day in m/f, based on 

increased liver weights and hepatocellular 

microscopic findings (necrosis and intracellular 

pigment accumulation in Kupffer 

cells/macrophages in males; intra 

hepatocellular erythrocytes in males and 

females). At 7000 ppm, body weight gain was 

decreased only during the first 90 days for 

males and from days 0-364 and 0-546 for 

females.

No evidence of carcinogenicity. A statistically 

significant increase in hepatocellular adenomas 

observed in males at 2500 and 7500 ppm was 

within historical control range.
Page 23 of 32

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Triflusulfuron-Methyl

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.4300 Combined 

carcinogenicity/chr

onic toxicity (rat)

MRID 42991413 (1993)

Acceptable/guideline

0, 10, 100, 750 or 1500 

ppm in the diet 

(males 0, 0.406, 2.44, 30.6 

or 64.5 mg/kg/day; 

females 0, 0.546, 3.28, 

41.5 or 87.7 mg/kg/day)

NOAEL = 2.44/3.28 mg/kg/day in m/f

LOAEL = 30.6/41.5 mg/kg/day in m/f, based 

on decreased body weight and weight gain, 

decreases in hematology parameters (primarily 

in males) and increased incidence of testicular 

interstitial cell hyperplasia. 

Evidence of carcinogenicity was observed as an 

increased incidence of testicular interstitial cell 

adenomas at 750 and 1500 ppm.

870.5100 Bacterial Gene 

Reverse Mutation 

S. typhimurium

Ames Assay, 

strains TA 98, 100, 

1535, 1537, 1538

MRID 42496846 (1992) 

Acceptable/guideline

62.5, 125, 250, 500 or 

1000 μg/plate (with and 

without S9 activation)

Negative. There was no evidence of induced 

reverse mutations with or without metabolic 

activation in 5 strains of Salmonella.

870.5100 Bacterial Gene 

Reverse Mutation

S. typhimurium

TA98, 100, 1535, 

1537 and 1538

42496849 (1991)

Acceptable/guideline

50, 100, 250, 500, 1000 or 

3000 μg/plate (with and 

without S9 activation)

Negative. There was no evidence of induced 

reverse mutation with or without metabolic 

activation in 5 strains of Salmonella.

870.5300 In Vitro

Mammalian Cell 

Forward Gene 

Mutation Chinese 

Hamster Ovary 

(CHO) cells

42496850 (1991) 

Acceptable/guideline

Tested up to 2000 μg/mL 

(with and without S9 

activation)

Negative. There was no evidence of induced 

forward mutations with or without activation.

870.5375 In Vitro

Mammalian 

Chromosome 

Aberration Human 

lymphocytes cells

42496852 (1991)

Acceptable/guideline

100 to 2000 μg/mL (with 

and without S9 activation)

Positive for induction of a treatment-related 

increase in the frequency of chromosomal 

aberrations at concentrations ≥1700 μg/mL in the 

presence of metabolic activation; inconclusive in 

the absence of metabolic activation.

870.5375 In Vitro

Mammalian 

Chromosome 

Aberration Human 

lymphocytes cells

42496845 (1992)

Acceptable/guideline

100 to 2000 μg/mL (with 

and without S9 activation)

Positive for induction of a treatment-related 

increase in the frequency of chromosomal 

aberrations at 2000 μg/mL in the presence of 

metabolic activation; inconclusive in the absence 

of metabolic activation. Follow-up assay to 

MRID 42496852.

870.5395 In vivo Mammalian 

Micronucleus 

Assay Mouse (male 

and female)

42496853 (1991)

Acceptable/guideline

Tested up to 5000 mg/kg

Negative. There was no significant increase in 

the frequency of micronucleated polychromatic 

erythrocytes in bone marrow of mice up to the 

limit dose at 24, 48 or 72 hr postdosing.

870.6200a Acute neurotoxicity 

(rat)

43398601 (1994)

Acceptable/guideline

0, 500, 1000 or 2000 

mg/kg

NOAEL≥2000 mg/kg (HDT)

LOAEL >2000 mg/kg – not established
Page 24 of 32

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Triflusulfuron-Methyl

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.6200b Subchronic 

neurotoxicity (rat)

43398602 (1994)

Acceptable/guideline

0, 100, 750, 1500 or 3000 

ppm in the diet

(males 0, 6.1, 46.1, 92.7 

or 186.2 mg/kg/day;

females 0, 7.1, 51.6, 104.1 

or 205.2 mg/kg/day)

NOAEL = 92.7 mg/kg/day (males) and 

 7.1 mg/kg/day (females)

LOAEL = 186.2 mg/kg/day (males) and 

 51.6 mg/kg/day (females), based on 

decreased body weight/body weight gain.

No evidence of neurotoxicity.

870.7485 Metabolism and 

pharmacokinetics

(rat)

42991416 (1992)

Acceptable/guideline

14C-triazine labeled 

triflusulfuron-methyl was 

administered as :

Low dose 25 mg/kg single 

oral dose; repeated low 

dose 25 mg/kg/day for 14 

days; high dose 250 

mg/kg, single oral dose. 

Ester 14C-carbonyl labeled 

triflusulfuron-methyl was 

also administered at 250 

mg/kg, single oral dose.

Evaluated for absorption, 

distribution, metabolism 

and excretion

Rate of absorption was unaffected by dose or 

dosing regimen but the extent of absorption 

was decreased at 250 mg/kg. Urine was the 

major route of excretion at 25 mg/kg but the 

primary route of excretion at 250 mg/kg was 

the feces. Excretion of radioactivity via 

expired air was negligible. By 120 hr postdosing, significant amounts of radioactivity 

remained in the liver. At 25 mg/kg the major 

urinary metabolite was N-desmethyl 

triflusulfuron-methyl (25-44% of AD), with 

females excreting higher levels than males of 

this metabolite. The N-hydroxymethyl 

metabolite was also found in urine (10-16% of 

AD). Triazine metabolites (triazine amine, Ndesmethyl triazine amine and N,N-bisdesmethyl triazine amine) were identified in 

liver as well as urine; in feces none of these 

metabolites represented more than 2% of AD. 

In rats dosed with the ester carbonyl-labeled 

triflusulfuron-methyl, methyl saccharin was a 

major metabolite in the urine and liver. 

NonGuidelineEvaluation of 

Mode of Action of 

Leydig Tumor Cell 

Induction

42991414 (1993)

Acceptable/nonguideline (as 

supplemental information)

(1)0, 1000, 1500 or 2000 

mg/kg/day for 15 days to 

male rats; examined for ;

(2)In vitro studiesinduction of male rat 

hepatic microsomal 

aromatase activity;

(3)in vitro evaluation of 

testosterone, progesterone 

and estradiol in rat Leydig 

cells ±hCG stimulation

(1) male rats showed decreased body weight, 

decreased absolute/relative accessory sex gland 

weights, and decreased estradiol levels. No 

effects on beta-oxidation or aromatase activity, 

or cytochrome p-450 content;

(2) hepatic microsomal activity showed dosedependent treatment-related decreases;

(3) in vitro incubation with triflusulfuronmethyl ±hCG caused decreased synthesis of 

estradiol and –hCG increased synthesis of 

testosterone .
Page 25 of 32

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 26 of 32

Appendix C. 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).

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 (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 inhalation dose received by occupational handlers is

compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational handlers. 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 27 of 32

Appendix D. Dietary Exposure/Risk Modeling Input and Output

Filename: C:\Users\tmorton\Documents\My Files\DEEM Files\129002 Triflusulfuron\129002 Chronic 

Food and Water.r08

Chemical: Triflusulfuron-methyl

RfD(Chronic): .0244 mg/kg bw/day NOEL(Chronic): 0 mg/kg bw/day

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

Date created/last modified: Program ver. 3.16, 

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

 EPA Crop Def Res Adj.Factors Comment

 Code Grp Commodity Name (ppm) #1 #2 

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

0101050000 1AB Beet, garden, roots 0.010000 1.000 1.000 

0101050001 1AB Beet, garden, roots-babyfood 0.010000 1.000 1.000 

0101052000 1A Beet, sugar 0.050000 1.000 1.000 

0101052001 1A Beet, sugar-babyfood 0.050000 1.000 1.000 

0101053000 1A Beet, sugar, molasses 0.050000 1.000 1.000 

0101053001 1A Beet, sugar, molasses-babyfood 0.050000 1.000 1.000 

0101100000 1AB Chicory, roots 0.050000 1.000 1.000 

0200051000 2 Beet, garden, tops 0.020000 1.000 1.000 

8601000000 86A Water, direct, all sources 0.020000 1.000 1.000 

8602000000 86B Water, indirect, all sources 0.020000 1.000 1.000 

US EPA Ver. 3.16, 03-08-d

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

Residue file name: C:\Users\tmorton\Documents\My Files\DEEM Files\129002 Triflusulfuron\129002 

Chronic Food and Water.R08

 Adjustment factor #2 NOT used.

Analysis Date 05-08-2015/10:15:25 Residue file dated: 05-08-2015/10:14:25

Reference dose (RfD, Chronic) = .0244 mg/kg bw/day

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

 Total exposure by population subgroup

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

 Total Exposure

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

 Population mg/kg Percent of 

 Subgroup body wt/day Rfd 

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

Total US Population 0.000433 1.8%

Hispanic 0.000414 1.7%

Non-Hisp-White 0.000445 1.8%

Non-Hisp-Black 0.000360 1.5%

Non-Hisp-Other 0.000497 2.0%

Nursing Infants 0.000384 1.6%

Non-Nursing Infants 0.001407 5.8%

Female 13+ PREG 0.000407 1.7%

Children 1-6 0.000574 2.4%

Children 7-12 0.000376 1.5%

Male 13-19 0.000303 1.2%

Female 13-19/NP 0.000336 1.4%

Male 20+ 0.000400 1.6%

Female 20+/NP 0.000450 1.8%

Seniors 55+ 0.000414 1.7%

All Infants 0.001091 4.5%

Female 13-50 0.000428 1.8%

Children 1-2 0.000639 2.6%

Children 3-5 0.000549 2.2%

Children 6-12 0.000396 1.6%

Youth 13-19 0.000319 1.3%

Adults 20-49 0.000428 1.8%

Adults 50-99 0.000422 1.7%

Female 13-49 0.000427 1.8%

-------------------------------------------------------------------------------
Page 28 of 32

Appendix E. Nomenclature and Physical/Chemical Properties

TABLE E.1. Triflusulfuron-Methyl Structure and Nomenclature.

Compound Chemical Structure

Common name Triflusulfuron-methyl

Company experimental name DPX 66037

IUPAC name methyl 2-[4-dimethylamino-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-

ylcarbamoylsulfamoyl]-m-toluic acid

CAS name methyl 2-[[[[[4-(dimethylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl]amino] 

carbonyl]amino]sulfonyl]-3-methylbenzoate

CAS # 126535-15-7

End-use product/(EP) UpBeet Herbicide

TABLE E.2 Physicochemical Properties of the Triflusulfuron-Methyl.

Parameter Value Reference

Melting point/range 155-158oC Petition Administrative 

Materials pH Not indicated

Density (g/mL) 1.45 absolute

0.56 (Bulk)

Water solubility ( 25°C) pH ppm

3 1.0

5 2.7

7 110

9 11 000

Low solubility at pH3 and pH 5; soluble at 

pH 7; very soluble at pH 9. Solubility 

increases with increasing pH.

Solvent solubility (mg/L) solvent mg/L

hexane <0.0016

octanol 0.026

toluene 2.0

methanol 7.0

ethyl acetate 27

acetonitrile 80

acetone 120

chloroform 160

methylene chloride 580

Vapor pressure at 25°C <1 x 10-7 mm Hg

SO2NHCONH

N

N

N

N(CH3)

2

CH3

OCH2CF3

CO2CH3
Page 29 of 32

TABLE E.2 Physicochemical Properties of the Triflusulfuron-Methyl.

Parameter Value Reference

A relatively non-volatile compound; low 

potential for losses due to volatilization.

Dissociation constant (pKa) 4.4

This compound will dissociate and exist in its 

anionic form at most environmentally 

relevant pHs.

Octanol/water partition coefficient (KOW) pH Kow at 25°C

5 220

7 9.2

9 0.86

Low potential for bioaccumulation in biota.

UV/visible absorption spectrum λmax = 395 nm

absorption at λ>400 nm is not anticipated

Potential to absorb sunlight in the UV/visible 

range of 290-400 nm.
Page 30 of 32

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 them8. [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 triflusulfuron-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 available910. 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 

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. 

 

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

9 http://www.agdrift.com/

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

assessors should be aware and characterize these appropriately.
Page 31 of 32

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.
Page 32 of 32

Appendix G. Analytical Standards Status

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

National Pesticide Standards Repository (NPSR) and have an expiration date of 12/2/2015 (email 

communication between G. Verdin and T. Morton, 5/26/2015). The registrant is required to 

maintain reasonable amounts of the reference standards for triflusulfuron-methyl in the NPSR as 

long as tolerances remain published in 40 CFR §180.492. When necessary, new reference 

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

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

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

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

returned to the registrant.

 USEPA

 National Pesticide Standards Repository

 Analytical Chemistry Branch/BEAD/OPP

 701 Mapes Road

 Fort George G. Meade, MD 20755-5350

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

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

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

COAs, may be required periodically if supplies are exhausted, if the standards expire, or if 

decomposition occurs during storage. Material Safety Data Sheets (MSDSs) must accompany all 

analytical standards as specified by the Occupational Safety and Health Administration (OSHA) 

in 29CFR §1910.1200.