UNITED STATES ENV IRO MENTAL PROTECT I ON AGENCY

WASHINGTON, D.C. 20460

OFF I CE OF C H E M I CA L SA FETY AN D POLL U T I ON PR EVENT I ON



### MEMORANDUM

Date : September 1 5, 2015



### SUB J ECT : Tr itlusulfuron-M e th y l: Human Health Risk Assessmen t in Sup p o rt of Registration Review.



### PC C od e: I 29002 

### Dec i sio n No.: 503362 

### DP Bar co d e: D 426786 

### Sect ion 3 

### Registration No s .: 352-569;
352-583 

### Petition No.: NA 

### Re g ulato ry Actio n : Registration Review 

### Case No.: 7236 

### Ri s k Assess ment Type: S in g l e Chemical Aggregate 

### TXRNo.: NA 

### CAS No.: 1 26535-15-7 

### 40 

### CF R : 180.492 

### MRID No.: NA



### F ROM :

THROUGH:

TO : Jessica Kidwell

, Ri sk Assessor 

# (L, ili11 

## tt....

# ~.e,,l**~** Abda llah Khasawinah. Ph.D

.,

## T4:c~~~gist. // 

# C<

I van Nieves. Occupational/Res i dential Exposure Assessor
Thurston Morton

, Chemist and Dietary Exposure Assess )
Ri sk Assessme nt Branch IV
Health Effects Division (7509P)

Cha rl es Sm i th

, Acting Branch Ch i ef 

# C**~** Risk Assessment Branch I V
Health Effects Division (7509P)

Matthew Manupella, C h emical Review Ma n ager Kev in Coste ll o, Branch Ch i ef
Risk Management a nd Impl ementation Branch 2 ( R M I B 2)
Pesticide Re-Evaluation Di vision (7508 P )

As part of Registration R eview

, PRD of the Office of Pesticide Programs 

### (OP P ) has r equested
that HED eva lu ate the hazard and exposure data and conduct dietary, occupat ion a l and
residen tial ex p osure assessments, as needed, to estimate the risk to human hea lth that will r esu l t from the curre ntl y registered uses of p est i cides. This memorandum serves as II E D ' s draft hum an health risk assessment of the dietary

, occupationa l

, and non-occupational expos ur e, a nd aggregate risk from the registered uses 

### of tri flusulfuron-mcthyl.



### Page l of 32

### Since the last human health ri sk assessment and scoping document. the fo llowin g updates have been inc01poratedjor trijlusulfuron-methyl.

1) The immunoloxicity and inhalation to xicity study requirements have been waived. 2) An endpoint and point of departure have been selected.from the 90-day oral toxicity s tud y 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 scree nin g -l evel dietary exposure / risk est imat es.



### Pa ge 

### 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 Combin ed 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 Toxicol ogy 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 Des cription

................................ ................................ ......... 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), triflusulfuron

methyl is currently approved for use on sugar beet, garden beet, and chicory/Belgium endive for selective postemergence control, or partial control, of broadleaf and gr ass 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 appl ied 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 201 2 ( S. Recore

, D 399195

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

, h owever, 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 , 6/7/2 012 )

.
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 a ssess exposure from spray drift; dermal risks are not anticipated. All other endpoints/PODs selected for risk assessment remain the same as in the previ ous 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 f or 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 belo w 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 exposur e 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, i ncidental oral risk estimates for children 1 to <2 years old were calculated

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

.

In the ca se 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; there fore, HED relie d 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 hand led. 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 9 200 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 n eed 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 post

application exposures.

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

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 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 Inter im 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. Complianc e 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 a re provided in Appendix E

.

3.2 Pesticide Use Pattern and Anticipated Exposure Pathways

Triflusulfuron

- methyl is m arketed as UpBeet, a dry flowable (DF) formulation containing 50% active ingredient (ai), triflusulfuron

- methyl is currently approved f or use on sugar beet, garden beet, and chicory

/Belgium endive using broadcast (ground

- or aerial

- based) or band application methods at seasonal rates of u p 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) o f 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 i ntermediate

- term ( i.e., 1 to 6 months) ; long

- term exposures (greater than 6 months) are not anticipated. The PPE statement s on registered labels require applicators, flaggers and other handlers t o 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 triflusulfuro n

- 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 RTI 1

(days) Max.

Seasonal Applic.

Rate (lb ai/A) PHI 2

(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 post

emergent spray when garden
beets are at the following stages: 2

- 4 leaf stage; 4

- 6 leaf stage; and 6

- 8 leaf stage. 0.01 6 3 See appli

cation 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

2 PHI = 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 pa rt 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 o f 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 Ind ividuals (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 t riflusulfuron

- methyl is complete a nd adequate for risk

assessment. Immunotoxicity and inhalation studies are not available for triflusulfuron

- methyl, as required in accordance with the current 40 CFR P art 158 Toxicology Data Requirements. However, the Hazard and Science Policy Council (HAS POC) 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 h ave been received and the endpoints selected for the previous ri sk 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 testicu lar 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 we re 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 cytotoxici ty. 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 r at 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 signif

icant 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, t riflusulfuron

- 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 non

linear approach (i.e., RfD) was recommended to adequately account for all chronic toxicity, including carcinogenicity, that could result from exposure to tri flusulfuron

- methyl.

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

HED has recommend ed that the required 10X Food Quality Protection Act ( FQPA S afety F actor (SF) be reduced to 1 x 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 D eparture 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 T able 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

- Occupation al 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 UF A = 10x

UF H = 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 UF A =10x

UF H =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 Intermed iate

Term (1 to 6 months) NOAEL =

6.56 mg/kg/day UF A =10x

UF H =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 f or 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 dat a 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. UF A = e xtrapolation from animal to human (interspecies). UF H = 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 a nd FFDCA, EPA reviews nu m erous studies to assess potential adverse

outco m es f

r om exposure to che m icals. Collecti v ely, these studies inclu d e acute, subchronic and chronic toxicity, including ass e ss m ents of carcinogenicity, n e urotoxicity, develop m ental, reproductive, and general or syste m ic toxicity. These studies include e ndpoints which m ay be susceptible to endocrine influ e nce, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual m aturati o n, fertility, pregnancy rates, reproductive loss, and sex rati o s in offspring. For ecol o gical h azard assess m ents, EPA evaluates ac u te tests an d chronic s t u d ies t h at a s sess growth, develop m ental and repro d uctive effects in different

taxono m ic groups. As part of its most recent registration decision for triflusulfuron

- methyl, EPA reviewed these data and selected the m o st sen s iti v e endpoints for re levant risk

assess m ent scenarios f

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

- methyl is subject to the endocrine screening part of the Endocrine D i sruptor Screening Program (EDSP).

EPA has developed the E DSP to deter m ine whether certain substances (including pesticide active and other ingredients) m ay have an effect in hu m ans or wildli f e si m ilar to an eff

ect produced by a “naturally occurring estrogen, or o t her such e n docrine effec t s as the Ad m i nistrator m ay designate.” The EDSP e mploys a two

- tiered approach to m aking t h e statutorily required deter m inations. Tier 1 consists of a battery of 11 screening assays to i d enti f y the pote n ti a l of a che m ical substance to i n teract with the estro g en, androgen, or thyr oid (E, A, or T) hormonal syste m s. Che m icals that go t h rough Tier 1 screening and are found to have the potential to int e ract with E, A, or T hor m onal syste m s will proceed to the next sta g e of the EDSP where EPA will deter m ine which, if any, of t h e Tier 2 tests are neces s ary bas e d on the available data. Tier 2 testing is de signed to id e nti f y any adverse endocrine

- related ef f ects caused by the su b stance, and establish a dose

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

Under FFDCA section 408(p), the Agency m ust screen all pesticide che m icals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 che m icals, which contains 58 pes t icide active ingredien t s and 9 inert ingredi ents. A second list of ch e m icals identified for EDSP screening was published on June 14, 2013 1 

### and includes

so m e pesticides scheduled for registration review and che m icals found in water

. Neither of these lists should be construed as a list of kno w n or li kely endocrine disruptors.

For further info r m ation on the status of the EDSP, the policies and procedures, the li s ts of

c h e m icals, f

uture lists, the test g u ideli n es and the Tier 1 screening battery, please visit our website 2



### .

1 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of chemicals.

2 http://www.epa.gov/endo/

### 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. EF ED 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

- scree n 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 sa me 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 us ed the refined

- screen post

breakthrough 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 as sessment, 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 usin g 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 inp uts 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

- M ethyl

. Chronic Estimates

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

Total US Population 0. 0 00433 1.8 All Infants (< 1 year old) 0. 001091 4.5 Children 1

- 2 years old 0. 0 00639 2.6 Children 3

- 5 years old 0. 0 00549 2.2 Children 6

- 12 years old 0. 00 0396 1.6 Youth 13

- 19 years old 0. 00 0319 1.3 Adults 20

- 49 years old 0. 0 00428 1.8 Adults 50

- 99 years old 0. 0 00422 1.7 Female 13

- 49 years old 0. 0 00427 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 dr ift 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

- f oo t wide lawns coupled with methods employed for residential risk assessments for turf products. Triflusulf uron

- 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

- to

medium spray type and a series of other parameters which will be described in more detail belo w (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. Th e 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) TTR 1 (ug/cm 2 ) 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 Exposu re

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 deve loped 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 furt her 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 estimat es 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, Pesti cide Cumulative Risk Assessment: Framework for Screening Analysis [http://www.epa.gov/oppfead1/cb/csb_page/updates/2015/framework

- for

- screening

analysis.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

group s (CMGs) [ 4 

### and 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,

a nd 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, occupatio nal 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 exp osure 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 da ta), 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 Exposu re Surrogate Reference Table 6 

### .” HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 7



### .

Area Treated : The area treated inputs were based on the Science Advisory Council for Exposure Poli cy 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 Level a Inhalation Unit E xposure b (mg/lb ai) Application

Rate c (lb ai/A) Area Treated d Inhalation Dose e (mg/kg/day) Total MOE f

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 Scienc e 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 (6.5 6 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 ex pert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/ scipoly/SAP/meetings/2009/120109meeting.html). The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

OPP

- 2014

- 0219). During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route

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

- methyl

.
In addition, the Agency is continuing t o 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

- appl ication 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 exp osure 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

- applicat ion 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 i s 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 classi fied 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 a s 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 objection s 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 t he 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.

1 2 .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 D 388621 4/13/2011 Triflusulfuro n

- Methyl : Revised Human Health Risk Assessment for Proposed Use i n Garden Beet.

A. Khasawinah, J. Kidwell, T. Morton, S. Hummel, I. Nieves D 399195 5/8/2012 Triflusulfuron

- Methyl : Human Health Risk Scoping Document in Support of Registration Review

S.Recore D 399193 5 /03/20 12 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 triflus ulfuron

- 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 waived 1 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 waived 2

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) LD 50 > 5000 mg/kg (both sexes) IV

870.1200 Acute dermal

- rabbit 42496826 (1991) LD 50 > 2000 mg/kg (both sexes) III

870.1200 Acute dermal

- rat 42496825 (1991) LD 50 > 2000 mg/kg (both sexes) III

870.1300 Acute inhalation

- rat 42496828 (1991) LC 50 > 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 42 4 9 6840 (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 ef fects 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 Dev elopmental 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/bod y 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 m g/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 erythrocyt es 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 obse rved 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 (prim arily 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 concentra tions ≥ 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 4 2496852.

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

14 C

- 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 14 C

- 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 majo r 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 post

dosing, 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 amin e, N

desmethyl triazine amine and N,N

- bis

desmethyl 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 s accharin was a major metabolite in the urine and liver.

Non

Guideline Evaluation of

Mode of Action of Leydig Tumor Cell Induction 42991414 (1993)

Acceptable/non

guideline (as supplemental information) (1)0, 1000, 1500 or 2000 mg/kg/day for 15 days to male rats; examined for ; (2) In vitro studies

induction 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 do se

dependent treatment

- related decreases; (3 ) in vitro incubation with triflusulfuron

methyl ±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

req uirements. 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 = e xposure (mg ai/day),
UE = u nit e xposure (μg ai/lb ai),
AR = m aximum application rate according to registered label s (lb ai / A), and
A = a rea 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 = e xposure (mg ai/day),
AF = absorption fa ctor (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 a re 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, molasse s

- 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 fi le 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 Perce nt 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

- 158 o C 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

### 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 (pK a ) 4.4

This compound will dissociate and exist in its anionic form at most environmentally relevant pHs.

Octanol/water partition coefficient (K OW ) pH K ow at 25°C 5 220 7 9.2
9 0.86 Low potential for bioaccumulation in biota.

UV/visible absorption spectrum λ max = 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 off

target and can lead to exposures to those the chemical may di rectly contact. Sprays can also deposit on surfaces where individuals come into contact with residues on these surfaces, lead ing 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 re quirements intended to prevent them 8



### . [ 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 t he 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 deposi ted 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 fr om 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

s pecific label guidance that defines application parameters is not available 9 10 

### . 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 screeni ng 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 represe nt 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 wate r 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., a erial applications are not allowed). Section 6.1 .1 provides the screening level drift related risk estimates.

8 This appro ach 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 chara cterize 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 acc ount 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 registr ant 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 f ull 9

- digit ZIP Code is required, or the mail will be returned to the registrant.

USEPA National Pesticide Standards Repository Analytical Chemistry Branch/B EAD/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 im purities, 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 oc curs 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.