UNITED STA TES ENVIRONMENT AL PROTE C TION AGENCY WASHINGTON

, D.C. 20460 OFFICE OF CHEM I CAL SAFETY AND POLLUTION PREV ENT IO N



### MEMORANDUM

D a t e : 15 September 2015



### SUBJECT: Tr ibenuron meth y l. Draft Human Health Risk Assessment in Support of Registration Revi ew

.



### F ROM:

THRO UG H:

TO: PC Co d e: 1 288 87 DP Barcode: 0421388 Deci s i on N o .: 492900 Re g i s tration No.: NA Petition No.: NA Case No

. : 7217 Ri s k Assessme nt T y p e: Sing le C h e mi ca l Aggregate Regulatory Action: Re g istration R eview TXR No .: NA CAS No.: I 01200-48-0 MRID No. : No n e 40 C FR: 180 .451

Mic h ael A. Doherty

, Ph.D.

, Senior

# Chemist**~~** d<v"
Zaida Figueroa, Dr PH, Industrial H yg ieni .). Karlyn Middleton

, M.S.

, Toxicologist Ri sk Assessment Branch II H ealth Effec t s Di vision (7509 P)

Chr i stina Swartz, Branch C hief

# oQ;_.~ Risk Assessme nt Branch II Hea l th Effects Division (7509P)

Brittany Pruitt

, Chemical Rev i ew Manager Kelly Sherman, Branch Chief Risk Management and I mplementation Branch 3 (RMIB 3) Pe s ticid e Re-Evaluation Di vis ion (7508 P )

As part of registration review

, H E D has examined the toxicological and exposure databases for assessing hum a n hea l th risk s associated with tr i benuron methy l and conducted a new risk
assessment following current practices and policies. Significant changes relative to the la st risk

assessme nt (D358876

, B. H anson. 28 Septembe r 2009) include:

• Establishment of endpoints and points of departur e for assessing acute d i e tar y exposure for all populations as well as dermal and incidental oral exposure for chi l dren;

• Assessment of acu t e dietary and spray drift risks.

P age 1of36

### Page 2 of 36 Table of Contents

1.0 Executive Summary

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

................................ ................................ ................................ ....... 4 2.1 Tolerance Considerations

................................ ................................ ................................ 4 2.2 Label Considerations

................................ ................................ ................................ ....... 5 3.0 Introduction

................................ ................................ ................................ .......................... 5 3.1 Chemical Identity and Physical/Chemical Characteristics

................................ ............... 5 3.2 Pesticide Use Pattern and Anticipated Exposure Pathways

................................ ............. 5 3.3 Consideration of Environmental Justice

................................ ................................ .......... 7 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 Endo crine Disruptor Screening Program

................................ ................................ ....... 11 5.0 Dietary Exposure and Risk Assessment

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

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

................................ ................................ ................................ ...... 13 5.3 Dietary Exposure and Risk Estimates

................................ ................................ ............ 13 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

.............. 14 6.2 Residential Bystander Post

- Application Inhalation Exposure

................................ ....... 15 7.0 Aggregate Ex posure/Risk Characterization

................................ ................................ ....... 15 8.0 Cumulative Exposure/Risk Characterization

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

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

................................ ............................ 15 9.2 Occupational Post

- application Exposure/Risk Estimates

................................ .............. 19 9.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

........................... 19 9.2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

............................... 19 10.0 Public Health and Pesticide Epidemiology Data

................................ ............................... 22 11.0 Literature References

................................ ................................ ................................ ......... 23 12 .0 References

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

................................ ..... 24 Appendix B. Review of Human Research

................................ ................................ ................ 29 Appendix C. Occupational Algorithms

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

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

................................ ............... 34 Appendix F. Spray Drift Detailed Description

................................ ................................ ......... 35

### Page 3 of 36 1 .0 Executive Summary

Tribenuron methyl, methyl

- 2

- [[[[[4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl] methylamino] carbonyl] amino] sulfonyl], is a sulfonylurea herbicide that works via inhibition of acetolactate synthase (ALS)

. It is currently registered for use on cereal grains (barley, field corn, oats, rice, sorghum, and wheat), oilseed crops (canola, flax, and sunflower), soybeans, and cotton

. There is also a tolerance with regional registration for grass forage, fodder, and hay (except Bermuda grass forage and hay)

. It is registered for use as pre

- emergence, at

- planting, and post

- emerge nce burndown application(s) for the selective control of broadleaf weeds

. It is applied using common agricultural equipment (i.e., aerial, ground boom

, airblast )

. There are no registered residential uses for tribenuron methyl.

A human health scoping docu ment was conducted for tribenuron methyl in 2011 (D383555, D. Dotson); acute and subchronic neurotoxicity and immunotoxicity studies were identified as data
gaps

. These studies have since been submitted and reviewed, and the hazard assessment has been upda ted considering the new toxicology data. In addition, a subchronic inhalation toxicity and guideline dermal toxicity study are not available for tribenuron methyl, as required in the current Part 158 Guidelines (40 CFR Part 158)

. A non

- guideline 28

- day de rmal toxicity study was conducted in rabbits; however, testing was done only at the limit dose

. The Hazard and Science Policy Council (HASPOC) determined that the studies are not required at this time (TXR# 0056650). The toxicology database for tribenuron methyl is considered complete and adequate for risk assessment. For this assessment, an acute dietary risk assessment has been conducted based on results observed in the new acute neurotoxicity study

, and an incidental oral endpoint has been selected for a ssessing spray drift

. Also, the adult dermal and inhalation risk assessments have been revised based on results observed in the new subchronic neurotoxicity study. A separate children’s dermal risk assessment was conducted since a more appropriate endpoint for this population was identified in the reproduction study

. The chronic dietary endpoint/ point of departure ( POD ) selected for risk assessment remains the same as in previous assessments

. Th e current draft risk assessment incorporates all new ly received data and includes updates to hazard and exposure assessments, science policies

, and procedures

.

For dieta ry exposure, HED has conducted screening

- level acute and chronic dietary risk
assessment s for tribenuron methyl using tolerance

- level residues in foods and a screening

- level estimate of residues in drinking water

. The acute d ietary risk estimate s are <1 % of the acute population

- adjusted dose (PAD), and the chronic dietary risk estimates range from 6 to 18 % of the c hronic PAD; all dietary risk estimates are not of concern

.

There are no registered residential uses or uses resulting in direct residential exposure associated with triben uron methyl

. Therefo re, a quantitative residential exposure assessment was not perf ormed

.

T ribenuron methyl can be applied via ground and aerial equipment for the registered agricultural
uses, and there is the potential for indirect exposure to residues as a result of spray drift

. Therefore , HED estimated risks associated with spray drift. The highest exposure resulted from drift following tribenuron methyl applications using aerial equipment for children 1 < 2 years old [Margins of Exposure (MOEs ) ≥ 2,100 with a level of concern ( LOC ) =100 ] . There are no risks

### Page 4 of 36 of concern at the field’s edge (i.e., assuming a residential lawn is directly adjacent to a field where agricultural crops are grown and treated with agricultural equipment).

Since there are no residential exposure pathways for tribenuron methyl, the aggregate exposure and risk estimates are equivalent to the dietary exposure and risk estimates and do not exceed HED’s level of concern.

No chemical

- specific handler exposure data were submitted in support of this draft risk
assessment ; therefore, HED relied on the best available data to assess handler exposure

. Default assumptions established by HED ’s Science Advisory Council for Exposure (ExpoSAC) were used for parameters such as body weight and amount handled

. All occupational handler scenarios f

or the registered uses resulted in MOEs greater than the LOC of 100 at baseline level of risk mitigation (i.e., baseline attire with no gloves or respirator) or engineering controls for aerial applicators (i.e., enclosed cockpits) . The current label perso nal protective equipment ( PPE ) requires baseline attire, gloves, and coveralls; therefore, the calculated risk estimates are not of

concern , and no additional PPE is required.

Based on the Agency's current practices, a quantitative non

- cancer occupatio nal post

- application inhalation exposure assessment was not performed for tribenuron methyl

. If new policies or procedures are put into place, the Agency may revisit the need for such an assessment

. Post

application dermal exposure and risk estimates for the registered agricultural uses resulted in MOEs that are not of concern on day 0 (i.e., 12 hours following application)

. The restricted entry interval ( REI ) of 12 hours specified on the registered l abels is adequate to protect agricultural workers from post

- application exposures

.

HED has no t identified any risk concerns associated with the registered uses of tribenuron methyl

. There are no data gaps that would require submission of additional toxici ty , residue chemistry, or exposure data.

2.0 HED Recommendations

2.1 Tolerance Considerations

The residue definition for tolerance enforcement is tribenuron methyl only. The existing tolerances (40 CFR 180. 451 ) are supported by the available residue chemistry data

. At this time, there are Canadian Maximum Residue Levels ( MRL s ) for residues of tribenuron methyl in barley, oats, soybean seed, sunflower seed, and wheat at 0.05 ppm ; and flaxseed and rapeseed at 0.02 ppm. T here are no Codex MRLs for tribenuron methyl at this time . The U.S. tolerance s for residues of tribenuron methyl are harmonized with the ir counterpart Canadian MRL s

. No revisions to the existing U.S. tolerances are needed during registration review.

An analytical referenc e standard for tribenuron methyl is currently available in EPA’s National Pesticide Standards Repository (NPSR) and has an expiration date of 2 9 March 2019 (email communication between G. Verdin and J. Van Alstine, 5/11/2015)

. The registrant is required to maintain reasonable amounts of the reference standards for tribenuron methyl in the NPSR as long as tolerances remain published in 40 CFR §180. 4 51

. When necessary, new reference

### Page 5 of 36 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 r equired, 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 pro cedures employed, storage requirements, and special precautions for safe handling

. Replacement of standards, or updated COAs, may be required periodically if supplies are exhausted, if the standards expire, or if decomposition occurs during storage

. Safety Data Sheets (SDSs) must accompany all analytical standards as specified by the Occupational Safety and Health Administration (OSHA) in 29CFR §1910.1200

.

2.2 La bel C onsiderations

None.

3.0 Introduction

3.1 Chemical Identity and Physical/Chemical Characteristics

Tribenuron methyl { methyl

- 2

- [[[[[4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl] methylamino] carbonyl] amino] sulfonyl] } is a sulfonylurea herbicide (Group 2)

. The chemical properties of tribenuron methyl do not suggest that there are any particul ar exposure issues that warrant special consideration

. The technical

- grade compound has a dissociation constant of 4. 7 at 25°C

, making its water solubility dependent on pH, with low solubility below pH 3

. The potential for tribenuron methyl to partition in to fatty matrices is also, by extension, pH dependent; however, based on the octanol/water partitioning coefficient of 0.3 at pH 7 , such partitioning is unlikely to

occur at physiological pH levels

. Tribenuron methyl has a relatively low vapor pressure

, in dicating that inhalation of vapors is unlikely to be a significant source of exposure under ambient conditions

. The nomenclature and physical/chemical properties of tribenuron methyl are provided in Appendix E

.

3.2 Pesticide Use Pattern and Anticipated Exposure Pathways

Tribenuron methyl is registered for postemergence application to cereal grains, soybean, sunflower, and grasses grown for seed. It is also registered for use as a preemergence or post

harvest burn

- down broadcast applicat ion for numerous crops

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

. Tribenuron methyl is formulated as dry

-

### Page 6 of 36 flowable (DF) , dry

- granular (DG), and soluble

- granular (SG) end

- use products. There are 4 activ ely registered technical products and 17 active ly registered end

- use products, and they are applied as broadcast applications using common agricultural ground

, aerial , or chemigation equipment.

The registered use pattern s allows one or two application per se ason ; therefore , the duration of
exposure for occupational handlers 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 regist ered labels require applicators, flaggers and other handlers to wear the following : coveralls , shoes plus socks, and chemical

- resistant gloves

. The restricted entry interval (REI) on all labels is 12 hours.

Table 3.2

. Summary of Directions for Registered Uses of Tribenuron methyl. 1 Applic. Timing, Type, and Equip. Formulation and Products [EPA Reg No.] Applic. Rate (lb ai/A) Max. No. Applic. per

Season Max. Seasonal Applic. Rate

(lb ai/A) Use Directions and Limitations

Cereal Grains Between 2

- leaf and flag

- leaf stage Broadcast by ground boom, aerial, or chemigation DF, DG, SG [352

- 509, 352

- 538, 352

- 610, 352

- 611, 352

- 617, 352

- 632, 352

- 641, 352

- 661, 352

- 714, 352

- 715, 352

- 751, 352

- 875, 352

- 876, 352

- 899] 0.00234

- 0.03125 2 0.03125 14

- day retreatment interval Do not harvest within 45 days

of application.

Soybean Do not apply later than flowering Broadcast by ground boom, aerial, or chemigation SG [352

- 632] 0.0078

- 0.03125 1 0.03125

Sunflower After 2

- leaf stage but before bud formation Broadcast by ground boom, aerial, or chemigation DF, SG [352

- 509, 352

- 632] 0.0078

- 0.0156 0.03125 14

- day retreatment interval Do not apply within 70 days

of harvest

Grasses Grown for Seed 60 days preplant Broadcast by ground boom, aerial, or chemigation DF, SG [352

- 509, 352

- 632] 0.0047

- 0.0126 1 0.0156 For use only in ID, OR, UT, and WA

1 The information in this table was supplied by the registrants via the Pesticide Re

- Evaluation Division. It has not

un dergone review by the Biological and Economic Analysis Division for completeness or accuracy.

### Page 7 of 36 Table 3.2

. Summary of Directions for Registered Uses of Tribenuron methyl. 1 Applic. Timing, Type, and Equip. Formulation and Products [EPA Reg No.] Applic. Rate (lb ai/A) Max. No. Applic. per

Season Max. Seasonal Applic. Rate

(lb ai/A) Use Directions and Limitations

Preplant or Post

- Harvest Burn

- down Fall

- Spring Broadcast by ground boom, aerial, or chemigation DF, DG, SG [352

- 509, 352

- 538, 352

- 611, 352

- 617, 352

- 632, 352

- 635, 352

- 641, 352

- 661, 352

- 714, 352

- 755 AR

- 080014, 352

- 875, 352

- 889, 352

- 899] 0.00375

- 0.03125 2 0.03125 30

- day retreatment interval Preplant burn

- down After application, allow at

least: 7 days before planting soybean 14 days before planting
cotton 60 days before planting sugar beet and canola 45 days before planting other crops Fallow Spring

- Fall Broadcast by ground boom, aerial, or chemigation DF, DG, SG [352

- 538, 352

- 610, 352

- 611, 352

- 617, 352

- 641, 352

- 661, 352

- 714, 352

- 715, 352

- 751, 352

- 899] 0.002 6

- 0.0 094 1 0.0156 Apply to fallow fields when the majority of weeds have emerged and are actively growing After application, a llow at

least : 14 days before planting field corn, cotton , grain sorghum, rice, ory soybean 60 days before planting sugar beet and canola 45 days before planting other crops



### Exposure Pathways

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

. There are no registered uses for tribenuron methyl that will result in direct non

- dietary (i.e., residential)
exposures

. However, there is the potential for indirect exposure (incidental oral and dermal) to tribenuron methyl related to spray drift

. Agricultural workers may be exposed to tribenuron methyl during mixing, loading, and/or applying the herbicide (dermal and inhalation routes) as well as during post

- application activities (dermal route)

.

3.3 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," ( http://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf )

. As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures

. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential

### Page 8 of 36 sett ing

. Extensive data on food consumption patterns are compiled by the USDA under the National Health and Nutrition Examination Surveys

– What We Eat in America (NHANES

WWEIA) and are used in pesticide risk assessments for all registered food uses of a pesti cide

. 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 perfor med 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

- appl ication 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 tra ditional dietary patterns among specific subgroups.

4.0 Hazard Identification/Toxicology

The toxicology database for tribenuron methyl is adequate for risk assessment

. A s ubchronic inhalation toxicity and guideline dermal toxicity study are not available for tribenuron methyl, as required in accordance with the current Part 158 Guidelines (40 CFR Part 158)

. A non

- guideline 28

- day dermal toxicity study was conducted in rabbits ; however, testing was done only at the limit dose

. Based on the existing uses, t he Hazard and Science Policy Council (HASPOC) determined that the studies are not required at this time based on a weight of evidence approach and considering all of the available tribenuron methyl hazard and exposure information ( TXR# 0056650)

. Since the last risk assessment ( D358876, B. Hanson, 28 September 2009 ), new dermal penetration, acute and subchronic neurotoxicity, and immunotoxicity studies have been submitted for tribenuron methyl.

4.1 Summary of Toxicological Effects

Sign s of general toxicity, such as body weight changes and reduced food consumption, were observed in the majority of studies conducted

. No one particular organ appeared to be the target as effects on multiple organs were observed including the liver, heart, k idney, testes, and spleen

. S ubchronic oral exposure in rat s resulted in decreases in body weight gain, food consumption, and food efficiency; decreases in multiple organ weights ( heart, liver, kidney , testes, and spleen) ; and decreases in serum glucose, gl obulin, and cholesterol. Chronic exposure led to decreased absolute body weights , as well as polyarteritis in the pancreas, decreased secretion in seminal vesicles, lymphoid depletion in the spleen, and mineralization of the aorta and stomach (associated w ith glomerulonephropathy) in males

. Dilation of the renal pelvis and uterine horns, and retinal degeneration were seen in females

. There was also an increased incidence of mammary gland adenocarcinomas observed in females after chronic exposure

. As a resul t, tribenuron is classified as a “possible human carcinogen.” In mice, subchronic oral studies are not available; however, chronic exposure resulted in bilateral seminiferous degeneration and oligospermia in males, while decreased body weight was noted in females

. No treatment related tumors were observed in mice after chronic exposure

. In dogs, no treatment

- related effects were seen after subchronic oral exposure

, and effects after chronic exposure were limited to decreased body weight gain and increased serum bilirubin and aspartate aminotransferase ( AST ) in both sexes. No corroborative findings were observed for the elevated enzymes.

### Page 9 of 36 Dermal exposure resulted in treatment sit e lesions, hypokinesia, decreased body weights and food consumption, kidney pathology

, and death at the limit dose

. Clinical signs were observed in the acute neurotoxicity study only. Effects on motor activity and rearing were seen at the limit dose, alo ng with body weight changes and decreases in food consumption

. In the subchronic neurotoxicity study, decreased body weight/body weight gains, reduced food consumption, and food efficiency were observed

. No immunotoxicity was observed in the immunotoxicity study at doses up to the highest dose tested.

No evidence of increased susceptibility of the young was seen in developmental or reproduction studies with tribenuron methyl. In the rat developmental study , decreased fetal weights were observed at the mid dose while increased resorptions, mortality, and incomplete ossification were seen at the high dose

. In the rabbit developmental study, decreased fetal weights and abortions were observed

. However, all developmental effects were observed in the presenc e of comparable maternal toxicity

. In the rat reproduction study, offspring effects were limited to decreased body weight gain and spleen weights o bserved in the presence of comparable maternal toxicity

. Tribenuron methyl has low to moderate acute toxic ity via the oral (Toxicity Category IV), inhalation (Toxicity Category III), and dermal (Toxicity Category III) routes of exposure

. It is not a dermal irritant, but was found to be mildly irritating to the eye, and it is a skin sensitizer

.

Tribenuron is readily absorbed in rats

. The excretion half

- life for the low dose was 26 to 33 hours; the excretion half

- life for the high dose was 51 to 54 hours for males and 69 to 96 hours for females

. After 168 hours, the major route of excretion was the urine (2

- 4x feces)

. Although tissue levels increased with dose, there was no accumulation in any particular tissue

. Major metabolites in urine and feces included metsulfuron methyl, saccharin

, and O

- demethyl triazine amine

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

HED recommends that the FQPA Safety Factor be reduced to 1x for tribenuron methyl

. The toxicology database is complete, and there are no concerns/residual uncertainties with regard to
pre

- and/or postnatal toxicity, and no concern fo r neurotoxicity

. No increased quantitative/qualitative s usceptibility was seen in the rat and rabbit developmental and rat reproduction studies, and fetal/offspring effects were observed in the presence of comparable maternal effects. Additionally, there a re clear no

- observed adverse

- effect levels ( NOAELs ) for the effects seen in the studies

. Furthermore, the endpoints and points of departure selected for risk assessment are protective of the effects observed in the studies

. 4.3 Toxicity Endpoint and Point of Departure Selections

The toxicological endpoints and PODs have been updated cons idering the new toxicology data. An acute dietary risk assessment has been conducted based on results observed in the new acute neurotoxicity ( ACN ) study

, and an incid ental oral endpoint has been chosen for assessing spray drift

. Also, the adult dermal and inhalation risk assessments have been revised based on results

### Page 10 of 36 observed in the new subchronic neurotoxicity ( SCN ) study . A separate children’s dermal risk

assess ment was conducted since a more appropriate endpoint for this population was identified in the reproduction study

. The chronic dietary endpoint/POD selected for risk assessment remain s the same as in previous assessments

. It should be noted that the endp oints and POD s presented in the toxicology profile table ( A ppendix A ) have not been updated to comply with current policy regarding what constitutes an adverse effect

. The NOAELs and LOAELS have not been changed

. Therefore, the endpoints/PODs selected for risk assessment may be conservative

. The PODs selected for risk assessment are protective of the effects observed in the tribenuron methyl database.

A summary of toxicological doses and endpoints used in the tribenuron methyl human health risk
assessment s is presented below:

Table 4.3a. Toxicological Doses and Endpoints for Tribenuron Methyl for Use in Dietary and Non

- occupational 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 (All populations) NOAEL = 300 mg/kg/day UF A = 10X UF H = 10X FQPA SF = 1X Acute RfD =3 mg/kg/day

aPAD = 3 mg/kg/day Acute Neurotoxicity

- Rat. LOAEL=1000 mg/kg/day, based on body weight changes (BW loss in males, decreased BWG in females), reduced food consumption, and/or food efficiency, and transient effects on motor activity and rearing



### . Chronic Dietary (All Populations) NOAEL = 0.8 mg/kg/day UF A = 10X UF H = 10X FQPA SF = 1X Chronic RfD = 0.008 mg/kg/day

cPAD = 0.008 mg/kg/day Chronic

- Dog: LOAEL = 8.16 [M] mg/kg/day based on decreased body weight gain (20%), elevated bilirubin, AST, and increased urinary volume. Incidental oral (short

- term) NOAEL = 2.5 mg/kg/day UF A = 10X UF H = 10X FQPA SF = 1X Residential LOC for MOE = 100 2

- Generation Reproduction

- Ra t Offspring LOAEL= 25 mg/kg/day based on decreased pup weight (F1b up to 8%; F2b up to 9%) and decreased absolute and relative spleen weights in pups. Children Dermal, Short

- term (1

- 30 days) Intermediate

- term (1

- 6 months) NOAEL = 2.5 mg/kg/day DAF= 17.7% UF A = 10X UF H = 10X FQPA SF = 1X Residential LOC for MOE = 100 2

- Generation Reproduction

- Ra t Offspring LOAEL= 25 mg/kg/day based on decreased pup weight (F1b up to 8%; F2b up to 9%) and decreased absolute and relative spleen weights in pups. Adults Dermal, Short

- term (1

- 30 days) Intermediate

- term (1

- 6 months) NOAEL = 11.3 mg/kg/day DAF= 17.7% UF A = 10X UF H = 10X Residential LOC for MOE = 100 Subchronic neurotoxicity LOAEL=40.1 mg/kg/day, based on decreased body weight (up to 13% both sexes) and body weight gains, reduced food consumption, and food efficiency. Cancer Classified as Group C (possible human carcinogen)

. Not mutagenic

. The chronic RfD is considered to be protective of any potential cancer risk. Point of Departure = 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

.

### Page 11 of 36 LOAEL = lowest observed adverse effect level

. UF = uncertainty factor

. UF A = extrapolation from animal to human (interspecies)

. UF H = potential variation in sensitivity among members of the human population (intraspecies)

. FQPA SF = FQPA Safety Factor

. PAD = population adjusted dose (a = acute, c = chronic)

. RfD = reference dose

. N/A = not applicable.

Table 4.3b. Toxicological Doses and Endpoints for Tribenuron Methyl for Use in Occupational Risk Assessments

. Exposure/ Scenario Point of Departure Uncertainty Factors Level of Concern for Risk Assessment Study and Toxicological Effects

Adults Dermal, Short

- term (1

- 30 days) Intermediate

- term (1

- 6 months) NOAEL = 11.3 mg/kg/day DAF= 17.7% UF A = 10X UF H = 10X Occupational LOC for MOE = 100 Subchronic neurotoxicity LOAEL=40.1 mg/kg/day, based on decreased body weight (up to 13% both sexes) and body weight gains, reduced food consumption, and food efficiency. Inhalation Short

term (1

- 30 days) Intermediate

- term (1

- 6 months) NOAEL = 11.3 mg/kg/day UF A = 10X UF H = 10X Occupational LOC for MOE = 100 Subchronic neurotoxicity LOAEL=40.1 mg/kg/day, based on decreased body weight (up to 13% both sexes) and body weight gains, reduced food consumption, and food efficiency. Cancer (oral, dermal, inhalation) Classified as G roup C (possible human carcinogen)

. Not mutagenic

. Quantitative estimation of cancer risk is not recommended. 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

. DAF= Dermal absorption factor

. IAF=Inhalation absorption factor

. UF = uncertainty factor

. UF A = extrapolation from animal to human (interspecies)

. UF H = potential variation in sensitivity among members of the human population (intraspecies)

. MOE = margin of exposure

. LOC = level of concern

. N/A = not applicable.



### 4.4 Endocri ne 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, es trus 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 di fferent taxonomic groups

. As part of its most recent registration decision for tribenuron methyl, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database

. However, as requir ed by FFDCA section 408(p), tribenuron 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 ingredi ents) 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

### Page 12 of 36 systems

. chemicals that go through Tier 1 screening and are fou nd 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 a ny 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 Febr uary 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, 2013 2 

### and includ es some pesticides scheduled for Registration Review and chemicals found in water

. For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, p lease visit our website. 3



### 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 GroundWater (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 re sulted 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 appli cation 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 ass umptions 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 ( D 427429 G. Orr ick ). The acute and chronic dietary assessments for tribenuron methyl used the maximum daily concentration of 35 μg/L (0. 035 ppm) and the post

- breakthrough mean value of 23 μg/L (0. 023 ppm), respectively

.

Table 5.1. Results of PRZM

- GW Modeling for Tri benuron Methyl Estimated Drinking Water Concentrations.
Sulfonylurea (Use) PRZM

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

- breakthrough Mean (μg/L) Mean Breakthrough Time (yrs)
Tribenuron

- methyl (corn) NC cotton 35 23 6.1

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of chemicals.

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

### Page 13 of 36 5.2 Food Residue Profile

The residue of concern for dietary risk assessment of tribenuron methyl is the parent compound itself

. In conducting this assessment, HED has assumed tolerance

- level residues in the raw agricultural commodities and processed products of registered crops

, a nd that 100 percent of those crops are treated with tribenuron 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 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 exc eed 100% of the population adjusted dose (PAD)

. In the case of tribenuron methyl , the dietary risk estimates (Table 5.3) are not of concern. The acute estimate s are <1 % of the a PAD for all population groups

, and the chronic estimates range from 6 to 18 % of the cPAD across all representative population groups

. Because of the very conservative assumptions used in the analysis (tolerance level residues, 100 % crop treated,
upper

- bound modeled drinking water estimates), actual exposure and risk are expected to be much lower than those shown in Table 5 .3

. The listings of inputs and outputs to the assessment are included in Appendix D

.

Table 5 .3

. Summary of dietary exposure and risk estimates for tribenuron methyl

. Acute Estimates (95 th Percentile) Chronic Est imates

Population Group Exposure, mg/kg bw Risk, % aPAD Exposure, mg/kg bw/day Risk, % cPAD Total US Population 0.0021 <1 0.000 6 1 8 All Infants (< 1 year old) 0.0062 <1 0.0014 18 Children 1

- 2 years old 0.0033 <1 0.0010 12 Children 3

- 5 years old 0.0027 <1 0.00087 11 Children 6

- 12 years old 0.0021 <1 0.00063 8 Youth 13

- 19 years old 0.0017 <1 0.00048 6 Adults 20

- 49 years old 0.0020 <1 0.00059 7 Adults 50

- 99 years old 0.0018 <1 0.00056 7 Female 13

- 49 years old 0.0020 <1 0.00058 7



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

There are no registered residential uses or occupational/commercial uses resulting in residential
exposure associated with tribenuron

- methyl

. Therefo re, a quantitative residential exposure

asse ssment was not performed.

6.1 Spray Drift

A detailed description about HED’s spray drift policy and how to evaluate the drift potential and associated risks is available in Appendix F.

### Page 14 of 36 6.1. 1 Combined Risk Estimates from Lawn Deposition Adjacent to App lications

The spray drift risk estimates are based on an estimated deposited residue concentration as a result of the screening level agricultural application scenarios

. The potential risk estimates from these residues can be calculated using drift modeling onto 50 feet wide lawns coupled with methods employed for residential risk assessments for turf products

.

Tribenuron methyl is registered for use on cereal grains (barley, field corn, oats, rice, sorghum, and wheat), oilseed crops (canola, flax, and sunflower), soybeans, cotton , and for grass forage, fodder, and hay (except Bermuda grass forage and hay)

. Corn and soybean are the predominant registered agricultural usage crops with the highest application rates , and therefore, are considered prote ctive/ representative of the registered uses

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

Groundboom applications are based on the AgDrift option for high boom height and using very fine to fine spray type using the 90th perce ntile results.

Aerial applications are based on the use of AgDrift Tier 1 aerial option for a fine to medium spray type and a series of other parameters which will be described in more detail below (e.g., wind vector assumed to be 10 mph in a downwind di rection for entire application/drift event).

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

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

. The highest exposure resulted from drift following tribenuron applications using aerial equipment for children 1 to <2 years old (combined dermal + incidental oral MOEs ≥ 2,100, with a LOC =100)

. There are no risks of concern at the field’s edge (i.e., assuming a residential lawn is directl y adjacent to a field where agricultural crops are grown and treated with aerial, groundboom or airblast equipment)

. See Tables 6.1.1 and 6.1.2 for detailed results.

1 HED’s default assumption that 10% of the application is available for transfer on day 0 following the application and the residues dissipate at a rate of 10% each following day.

1 HED’s default assumption that 10% of the application is available for transfer on day 0 following the application and the residues dissipate at a rate of 10% each following day.

Table 6.1.1

. Adult Risk Estimates (MOEs) Related to Dermal Exposure to Spray Drift from Tribenuron Methyl

.

Crop/Rate

Group Spray Type/ Nozzle Configuration Appl. Rate (lb ai/A) TTR 1 (ug/cm 2 ) At Edge of the Field

Dermal Aerial Fine to Medium 0.03125 0.00347 21,000 Groundboom High Boom Very fine to Fine 29,000

Airblast Sparse 38,000

Table 6.1.2

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

.

Crop/Rate

Group Spray Type/ Nozzle Configuration Appl. Rate (lb ai/A) TTR 1 (ug/cm 2 ) At Edge of the Field
Dermal & Incidental Oral (Combined) Aerial Fine to Medium 0.03125 0.00347 2,100 Groundboom High Boom Very fine to Fine 2,900

Airblast Sparse 3,800

### Page 15 of 36 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 t o 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 4 

### on March 2, 2010

. The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis 5



### . During Registration Review, the agency will use this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required for tribenuron 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 tribenuron methyl , aggregate exposure and risk estimates are equivalent to the dietary exposure and risk estimates in Section 5, above, and are not of concern

.

8.0 Cumulative Exposure/Risk Characterization

In 2015, EPA’s Office of Pesticide Programs released a guidance document entitled, Pesticide Cumulative Risk Assessment: Framework for Screening Analysis [http://www.epa.gov/oppfead1/cb/csb_page/updates/2015/framework

- for

- screening

analy sis.html]. This document provides guidance on how to screen groups of pesticides for cumulative evaluation using a two

- step approach beginning with the evaluation of available toxicological information and if necessary, followed by a risk

- based screening approach. This framework supplements the existing guidance documents for establishing common mechanism groups (CMGs) 6 

### and conducting cumulative risk assessments (CRA) 7



### . The Agency has utilized this framework to evaluate the SUs of which orthosulfamuron is a member (J. D’Agostino; D428798; 9/9/15). Although the SUs share some chemical and toxicological characteristics, the toxicological database does not support a testable hypothesis for a common mechanism of action. No further mechanistic data are requir ed 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, occupatio nal handler exposure is expected from the registered uses

. The quantitative

4 http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

5 http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219

6 Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common Mechanism of Toxicity (USEPA, 1999)

7 Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity (USEPA, 2002)

### Page 16 of 36 exposure /risk assessment developed for occupational handlers is based on the scenarios listed in Table 9.1

. Based on the use pattern and agricultural practices, occupational exposu re from the registered food uses is expected to be short

- term (1

- 30 days) and intermediate

- term (i.e., 1

- 6 months) in duration

. Since the same endpoint and POD were selected for short

- and intermediate

- term durations, short

- term exposure and risk estimates are considered to be protective of intermediate

- term exposure and risk

. Long

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

Occupational Hand ler Exposure Data and Assumptions

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

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

Application Rate : The maxim um single application rates are listed in Table 3.2

. Refer to section 3.0 for a complete use pattern description.

Body Weight: The standard body weight for the general population (80 kg) was used for all dermal and inhalation exposure scenarios covered i n this risk assessment because the endpoint selected was not developmental and/or based on fetal effects

. Absorption Factor : Since no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure

. A dermal absorption factor of 17.7 % was used for the exposure assessment and is based on results from a dermal penetration study in rats.

Unit Exposures: It is the policy of HED to use the best availab le 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 p rotection provisions of FIFRA

. The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 8



### . ” HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 9



### .

Area Treated or Amount Handled: The inputs for area treated or amount handled were based on the Science Advisory Council for Exposure Policy 9.1: Standard Values for Daily Acres Treated in Agriculture (values are listed in Table 9.1)

. The acres treated for high acreage crops for aerial and groundboom applications, and orchard/vineyards for airblast applications were used as

scre ening for the occupational assessment.

Risk Estimate Equations : The algorithms used to estimate non

- cancer exposure and dose for occupational handlers can be found in Appendix C.

8 Available: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf

9 Available: http://www.epa.gov/pest icides/science/handler

- exposure

- data.html

### Page 17 of 36 Combining Exposures/Risk Estimates: Dermal and inhalation risk estimates were combined in this assessment, since the toxicological effects for these exposure routes were similar

. Dermal and inhalation risk estimates were combined using the following formula:

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

Summary of Occupational Handler Non

- Ca ncer Exposure and Risk Estimate

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

. All occupational handler scenarios for the registered uses resulted in total MOEs (dermal+inhalation) greater than the LOC of 100 at baseline level of risk mitigation (i.e., baseline attire with no gloves or respirator), or engineering controls for aerial applicators (i.e., enclosed cockpits) . The current label PPE requi res baseline attire, gloves, and coveralls; therefore, the calculated risk estimates are not of concern , and no additional PPE is required

. The lowest total MOE is 4 9 0 associated with total exposure during mixing/loading activities for a dispersible granul e formulation being applied aerially over up to 1,200 acres

. All other MOEs were higher ranging from 2,300 to 130 ,000

. The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure potential

. While HED presents quantitative risk estimates for human flaggers where appropriate, agricultural aviation has changed dramatically over the past two decades

. According the 2012 National Agricultural Aviation Association (NAAA) survey of their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily from the mid 1990’s

. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recen t (2012) NAAA survey

. The Agency will continue to monitor all available information sources to best assess and characterize the exposure potential for human flaggers in a gricultural aerial applications.

HED has no data to assess exposures to pilots using open cockpits

. The only data available reflects exposure to pilots in enclosed cockpits

. Therefore, risks to pilots are assessed using the engineering control ( i.e., enclosed cockpits) and baseline attire ( i.e., long

- sleeve shirt, long pants, shoes, and so cks); per the Agency’s Worker Protection Standard stipulations for engineering controls, pilots are not required to wear protective gloves for the duration of the application

. With this level of protection, there are no risk estimates of concern for applic ators.

Table 9.1

. Short

- term Handler Exposure and Risk Estimates for Tribenuron methyl

. Exposure Scenario Dermal Unit Exposure (ug/lb ai) [ Level of PPE ] ab Inhalation Unit Exposure (ug/lb ai) [ Level of PPE ] ab Application Rate c Area Treated d Dermal Dose e Dermal MOE f Inhalation Dose g Inhalation MOE h Total MOE i

Mixer/Loader Dry Flowable (Dispersible Granule) for 227 (Baseline) 8.96 ( Baseline ) 0.03125 lb ai/A 1,200 A 0.01880 600 0.0042 2,700 490

### Page 18 of 36 Table 9.1

. Short

- term Handler Exposure and Risk Estimates for Tribenuron methyl

. Exposure Scenario Dermal Unit Exposure (ug/lb ai) [ Level of PPE ] ab Inhalation Unit Exposure (ug/lb ai) [ Level of PPE ] ab Application Rate c Area Treated d Dermal Dose e Dermal MOE f Inhalation Dose g Inhalation MOE h Total MOE i

Aerial Application Dry Flowable (Dispersible Granule) for Groundboom Application 227 (Baseline) 8.96 ( Baseline ) 0.03125 lb ai/A 200 A 0.00140 3,600 0.0007 16,000 2,900

Dry Flowable (Dispersible Granule) for Airblast Application 227 (Baseline) 8.96 ( Baseline ) 0.03125 lb ai/A 40 A 0.000628 18,000 0.00014 81,000 15,000

Granular for Aerial Application 8.4 (Baseline) 1.7 (Baseline) 0.03125 lb ai/A 1 200 A 0.000697 16,000 0.000798 14,000 7,500

Granular for Tractor

- drawn Spreader 8.4 (Baseline) 1.7 (Baseline) 0.03125 lb ai/A 200 A 0.000116 97,000 0.000133 85,000 45,000

Applicator Sprays for Aerial Application 2.08 (Engineering Controls

– Enclosed Cockpit) 0.0049 (Engineering Controls

– Enclosed Cockpit) 0.03125 lb ai/A 1,200 A 0.000173 65,000 0.0000023 4,900,000 64,000

Sprays for Groundboom Application 78.6 (Baseline) 0.34 (Baseline) 0.03125 lb ai/A 200 A 0.00109 10,000 0.0000266 420,000 9,800

Sprays for Airblast Application 1,770 (Baseline) 4.71 (Baseline) 0.03125 lb ai/A 40 A 0.00489 2,300 0.0000736 150,000 2,300

Granules for Aerial Application 1.7 (Engineering Controls

– Enclosed Cockpit) 1.3 (Engineering Controls

– Enclosed Cockpit) 0.03125 lb ai/A 1200 A 0.000141 80,000 0.00061 19,000 15,000

Granules for Tractor

- drawn Spreader 9.9 (Baseline) 1.2 (Baseline) 0.03125 lb ai/A 200 A 0.000137 82,000 0.0000938 120,000 49,000

Flagger Sprays for Aerial Application 11 (Baseline) 0.35 (Baseline) 0.03125 lb ai/A 350 A 0.000266 42,000 0.0000479 240,000 36,000

Granules for Aerial Application 2.75 (Baseline) 0.15 (Baseline) 0.03125 lb ai/A 350 A 0.000067 170,000 0.0000205 550,000 130,000

a. Level of PPE : level of PPE represented by the numerical unit exposure. “ 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., enclosed cockpit for aerial applications ). Current label required PPE = coveralls, shoes plus socks, and chemical

- resistant gloves

. b. Based on the “ Occupational Pesticide Handler Unit Exposure Surrogate Reference Table ” (Fe bruary, 2015). c. Based on the maximum single application rates listed on registered labels (Table 3.2). d. Based on the Science Advisory Council for Exposure Policy 9.1: Standard Values for Daily Acres Treated in Agriculture

. e. Dermal Dose (mg/kg/day) = [Rate x UE x 0.0001 x Dermal Absorption (17.7%) x Area Treated]/BW (80 kg)

. f. Dermal MOE = Dermal NOAEL ( 11.3 mg/kg/day)/ Dermal Dose (mg/kg/day). LOC=100. g. Inhalation Dose (mg/kg/day) = [Rate x UE x 0.0001 x Area Treated ]/BW (80 kg).

### Page 19 of 36 h. Inhalation MOE = Inhalation NOAEL ( 11.3 mg/kg/day)/ Inhalation Dose (mg/kg/day). LOC=100. i. Total MOE = NOAEL (mg/kg/day)/ [Dermal + Inhalation Dose (mg/kg/day)]. LOC=100.



### 9.2 Occupational Post

- application Exposure/Risk Estimates

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re

entry exposure)

. Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as scouting for pests or harvesting

. Post

- application exposure levels vary over time and depend on such things as the type of activity, the nature of the crop or target that was treated, the type of pesticide application, and the chemical’s degradation properties

. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce the potential for post

- application exposure.

9.2.1 Occupational Post

- applicatio n 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 pestici des 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 (S AP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html)

. The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatil ization 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 f urther analysis is required for tribenuron

. 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 id entify 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 i nhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

9.2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

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

- application dermal risk assessment, including the following:

### Page 20 of 36 Exposure Duration: Based on the use pattern and agricultural practices, occupational post

application exposure from the registered food uses is expected to be sh ort

- term (1

- 30 days) and intermediate

- term (i.e., 1

- 6 months) in duration

. Since the same endpoint and POD were selected for short

- and intermediate

- term durations, short

- term exposure and risk estimates are considered to be protective of intermediate

- term exposure and risk

. Long

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

Transfer Coefficients: It is the policy of HED to use the best available data to assess post

application exposure

. Sources of generic post

- application data, used as su rrogate data in the absence of chemical

- specific data, are derived from the Agricultural Reentry Task Force (ARTF ) exposure monitoring studies, and, as proprietary data, are subject to the data protection provisions of FIFRA

. The standard values recommended for use in predicting post

- application exposure that are used in this assessment, known as “transfer coefficients”, are presented in the ExpoSAC Policy 3 10 

### ” which, along with additional information about the ARTF data, can b e found at the Agency website 11



### . Table 9.2.2.1 provides a summary of the anticipated high

- contact post

- application activities and associated transfer coefficients for the proposed crops/use sites. These activities were selected as a worst

- case assessment o f potential post

- application exposure, and are considered protective of all post

- application activities associated with these crops.

Table 9.2.2.1

. Anticipated High

- contact Post

- Application Activities and Dermal Transfer Coefficients.

Proposed Crops Policy Crop Group Category Crop Height Foliage Density Transfer Coefficients

(cm 2 /hr ) Activities

Corn, sweet, grain, processing Field, row, tall High Full 1,900 Irrigation (Hand set)

Corn, sweet, grain Field, row, tall High Full 8,800 Hand, Detasseling

Barley, Wheat, Soybean, Rice, Canola Field, row, medium Low Full 1,100 Scouting

Forage, Hay Field, row, medium High Full 1,900 Irrigation (Hand set)

Sunflower Field, row, tall Low/High Full 90 Scouting, Bird Control

Sorghum Field, row, tall High Full 210 Scouting

Cotton Field, row, medium Low Full 900 Harvesting Mechanical (Module Builder)

2400 Harvesting Mechanical (Picker Operator; Raker) 5050 Harvesting Mechanical (Tramper)



### Application Rate : The maximum single application rates are listed in Table 3.2

. Refer to section 3.0 for a complete use pattern description.

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

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

11 Available: http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.html

### Page 21 of 36 Dislodgeable Foliar Residues: Chemical

- specific dislodgeable foliar residue data have not been submitted for tribenuron during registration review

. T his assessment uses HED’s default assumption that 25% of the application is available for transfer on day 0 following the application and the residues dissipate at a rate of 10% each following day.

Ris k Estimate Equations : The algorithms used to estimate non

- cancer exposure and dose for occupational post

- application workers can be found in Appendix C.

Occupational Post

- application Non

- Cancer Dermal Risk Estimates

A summary of the post

- application exposure and risk estimates for the registered uses is provided in Table 9.2.2.2

. Only risk estimates for the highest contact activity for each crop and the highest application rates are shown below

. Post

- application dermal exposure and risk estimates for the scenarios shown below resulted in MOEs greater than 100 and are not of concern on day 0 (i.e., 12 hours following application)

. All other scenarios involving lower contact activities would have higher MOEs and are also not of concern.

A summary of the post

- application dermal exposure and risk estimates from use of tribenuron on cotton during harvesting activities is provided in Table 9.2.2.3

. Dislodgeable residue data for cotton bolls was not available for tribenuron; therefore, t he dislodgeable residue value for cotton bolls was estimated from the field trial residues in/on cotton gin byproducts . The field trial residue is an upper

- bound residue value collected at the pre

- harvest interval which represents the amount of residue in and on the cotto n boll; not just the amount of residue that could be dislodged. It is considered appropriate as an estimate of dislodgeable boll residue, and is used as a screening level approach to estimating exposure. Post

- application dermal exposure and risk estimate s resulted in MOEs greater than 100 and are not of concern

.

Table 9.2.2.2

. Occupational Post

- application Non

- Cancer Exposure and Risk Estimates for Tribenuron methyl

. Crop/Site Activities Transfer Coefficient (cm 2 /hr) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3

Short

- and Intermediate

- term Corn, sweet, grain, processing Irrigation (Hand set) 1,900 0.09 0.003 3,800
Corn, sweet, grain Hand, Detasseling 8,800 0.09 0.014 830

Barley, Wheat, Soybean, Rice, Canola Scouting 1,100 0.09 0.002 6,600

Forage, Hay Irrigation (Hand set) 1,900 0.09 0.003 3,800

Sunflower Scouting, Bird Control 90 0.09 0.0001 81,000 Sorghum Scouting 210 0.09 0.0003 35,000

1. DFR = Application Rate (0.03125 lb ai/A) × F × (1

- D) t × 4.54E8 μg/lb × 2.47E

- 8 acre/cm 2 ; where F = 0.25 and D = 0.10 per day.

2. Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × Dermal Absorption ( 17.7 %)] 

### ÷ BW ( 80 kg). 3. MOE = Dermal NOAEL ( 11.3 mg/kg/day) / Dermal Dose (mg/kg/day); LOC=100.

### Page 22 of 36 Table 9.2.2.3

. Post

- Application Exposure and Risk Estimates for use of Tribenuron on Cotton during Harvesting Activities.

Crop Maximum Application Rate (lb ai/A) Activity TC 1 (g cotton/hr) Days After Treatment Residue from Cotton Field Trial 2 (mg ai/g cotton) Daily Dose (mg/kg/d) 3 Dermal MOE 4

Short

- and Intermediate

- term

Cotton 0.009 Harvesting Mechanical (Module Builder) 900

133 0.00002 0.000319 35,000

Harvesting Mechanical (Picker Operator; Raker) 2,400 0.000869 13,000

Harvesting Mechanical (Tramper) 5,050 0.001788 6,200

1. Transfer Coefficients from HED Policy No. 3.0., Non

- Foliar Transfer Coefficient Table, March 2012 (p 122). 2. Residue Value from Cotton Field Trial adjusted to Max. Seasonal Application Rate (mg ai/g cotton) = (0.02 mg ai /kg cotton) (0.001 kg/g) ((0.009 lb ai/A)/(0.009 lb ai/A)) = 0.00002 mg ai/g cotton. 3. Dermal Dose (mg/kg/day) = [Cotton Field Trial Residue Value adjusted (mg ai/g cotton) x TC (g cotton/hr) x 8 hrs/day x DAF (17.7%)]/ BW (80 kg). 4. Dermal MOE = NOAEL ( 11.3 m g/kg/day)/Dermal Dose (mg/kg/day); LOC = 100.


### Restricted Entry Interval

The REI specified on the registered label s is 12 hours

. Tribenuron is classified as Toxicity Category III via the dermal route and Toxicity Category IV for skin irritation potential

. It is not a skin sensitizer

. Short

- and intermediate

- term post

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

- application activities

. Under 40 CFR 156.208 (c) (2) (iii), a ctive i ngredient s class ified as Toxicity Category III or IV for acute dermal, eye irritation and primary skin irritation are assigned a 12

- hour REI

. Therefore, the [156 subpart K] Worker Protection Statement interim REI of 12 hours is adequate to protect agricultural workers fro m post

- application exposures to tribenuron

. The REI specified on the current labels is protective.

10.0 Public Health and Pesticide Epidemiology Data D42 581 6 , S. Recore, 24 March 2015

Tribenuron methyl was previously reviewed in 2010 (S. Recore, 11/30/20 10, D383633)

. At the time, there were no tribenuron methyl incidents found in Main IDS and eight incidents reported to Aggregate IDS from January 1, 2002 to May 27, 2010

. Upon review of these incidents, it was concluded that “ Based on the low frequency and severity of incident cases, there does not appear to be a concern at this time that would warrant further investigation. ”

The current IDS analysis from January 1, 2010 through March 10, 2015, shows no incidents reported involving tribenuron methyl in M ain IDS and six incidents reported to Aggregate IDS

. Further, a query of SENSOR

- Pesticides 1998

- 2011 identifies eight cases involving multiple active ingredients, including tribenuron methyl. These incidents were classified as low severity.

Based on the low frequency and mostly low severity of incident cases reported for tribenuron methyl in both IDS and NIOSH SENSOR

- Pesticides, there does not appear to be a concern at

### Page 23 of 36 this time that would warrant further investigation

. The Agency will contin ue to monitor the incident information and if a concern is triggered, additional analysis will be conducted.

The Agricultural Health Study (AHS) is also a potential source of information associated with human health effects associated with certain pestici des

. Tribenuron methyl is not included in the AHS, and therefore that study does not provide information for this assessment

.

11.0 Literature References

A literature search was performed for tribenuron m ethyl

. The search did not reveal information that would impact the current risk assessment

.

1 2 .0 References

Author Barcode Date Title Hanson, B. D358876 28 Sept. 2009 Tribenuron methyl. Human Health Risk Assessment for the Proposed Use of Tribenuron methyl on Corn and Soybean Dotson, D. et al. D383555 2 March 2011 Tribenuron Methyl. Human Health Assessment Scoping Document in Support of Registration Review. Van Alstine, J. TXR# 0056650 17 June 2013 Tribenuron methyl: Summary of Hazard and Science Policy Council (HASPOC) Meeting of April 25, 2013: Recommendations on the Requirements for Subchronic Inhalation and Subchronic Dermal Studies. Recore, S. D425816 24 March 2015 Tribenuron

- methyl: Tier 1 Update Review of Human Incidents/Epidemiology for Draft Risk Assessment G. Orrick D427429 

### 8/12/2015 Drinking Water Exposure Assessment for the Registration Review of 22 Sulfonylurea Herbicides

### Page 24 of 36 Appendix A. Toxicology Data Requirements and Toxicology Profile

A.1 . Toxicity Requirements

The toxicology requirements (40 CFR 158.340) for tribenuron m ethyl are presented below.

Test Technical Required Satisfied 870.1100 Acute Oral Toxicity 870.1200 Acute Dermal Toxicity 870.1300 Acute Inhalation Toxicity 870.2400 Primary Eye Irritation 870.2500 Primary Dermal Irritation 870.2600 Dermal Sensitization Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

870.3100 Oral Subchronic (rodent) 870.3150 Oral Subchronic (nonrodent) 870.3200 21

- Day Dermal 870.3250 90

- Day Dermal 870.3465 21/90

- Day Inhalation Yes Yes Yes No Yes Yes Yes Not required * No + Not required *

870.3700a Developmental Toxicity (rodent) 870.3700b Developmental Toxicity (nonrodent) 870.3800 Reproduction Yes Yes Yes Yes Yes Yes 870.4100a Chronic Toxicity (rodent) 870.4100b Chronic Toxicity (nonrodent) 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 870.5385 Mutagenicity

— Mouse Micronucleus 870.5550 Mutagenicity

— Unscheduled DNA Synthesis Yes Yes Yes No Yes Yes Yes

--- 870.6200a Acute Neurotoxicity Screening Battery (rat) 870.6200b 90

- Day Neurotoxicity Screening Battery (rat) 870.6300 Developmental Neurotoxicity Yes Yes No Yes Yes No

870.7485 General Metabolism 870.7600 Dermal Penetration 870.7800 Immunotoxicity Yes No Yes Yes Yes

* The Hazard and Science Policy Council (HASPOC) determined that subchronic inhalation and immunotoxicity studies are not required (TXR#s 0056650 ). + A non

- guideline 28

- day dermal toxicity study was conducted in rabbits ; however, testing was done only at the limit dose.

### Page 25 of 36 A.2. Toxicity Profil es

TABLE A.2. 1 Acute Toxicity Profile

- Tribenuron Methyl (Technical Grade) 

### Test MRID Results Category
Oral LD 50 - rat 00149670 LD 50 >5000 mg/kg (limit test) IV Dermal LD 50 - rabbit 00148632 LD 50 >2000 mg/kg (limit test) III Inhalation LC 50 - rat 00148634 LC50 >6.7 mg/L gravimetric concentration (4

- hour nose

- only limit test); MMAD = 3.5 μm III Eye Irritation

- rabbit 40357401 Mild irritation in washed and unwashed eyes, redness with vessel injection at 1 and 4 hours. IV Dermal irritation

- rabbit 40357402 Non

- irritating IV Dermal sensitization

- guinea pig 42364302 Sensitizer Not applicable



### Table A.2.2. Subchronic, chronic, and Other Toxicology Profile for Tribenuron Methyl
Guide line Study Title MRID Dose Levels Results

870.3100 90

- Day oral toxicity, Rat 00148638 0, 100, 1750, 5000 ppm NOAEL=100 ppm (7/8 mg/kg/day, M/F, respectively) LOAEL=1750 ppm (118/135 mg/kg/day, M/F, respectively) for decreased body weight gain, food consumption and food efficiency; decreased absolute heart, liver, and kidney weights; increase relative brain, heart, liver, kidney, testes, and spleen weights; decreased serum glucose and globulin; no histopathologic lesions; likely cachexia 870.3150 13

- week subchronic oral toxicity, Dog 00148639 0, 50, 500, 2500 ppm NOAEL = 2500 ppm (73.3/78.0 mg/kg/day in M/F, respectively) HDT 870.3200 28

- Day Dermal, Rabbit 42243101 Limit dose, 1000 mg/kg/day (only dose tested), 1000 mg/kg/day (only dose tested), resulted in serious toxicity and death. Toxicity included treatment site lesions, hypokinesia, decreased body weights and food consumption, and kidney pathology, but the cause of death could not be determined. Although this study is classified as Core Supplementary, another study is not needed. Worker exposure is expecte d to be 4

- 5 orders of magnitude lower than the limit dose. 870.3700a Developmental Toxicity, Rat 00148640 0, 20, 125 or 500 mg/kg/day Maternal NOAEL=20 mg/kg/day Maternal LOAEL=125 mg/kg/day ( decreased maternal body weight gain and food consumption, increased liver

to

- body weight ratios (at the highest dose), and excess salivation) Developmental NOAEL=20 mg/kg/day

### Page 26 of 36 Table A.2.2. Subchronic, chronic, and Other Toxicology Profile for Tribenuron Methyl
Guide line Study Title MRID Dose Levels Results

Developmental LOAEL=125 mg/kg/day , based on decreased body weight) At 500 mg/kg/day (HDT) there were increased resorption, fet al deaths, and incomplete ossifications. 870.3700b Developmental Toxicity, Rabbit 40245514 0, 5, 20, or 80 mg/kg/day Maternal NOAEL=20 mg/kg/day Maternal LOAEL=80 mg/kg/day

, based on decreased food consumption, increased abortions (GD 19

- 29)) Developmental NOAEL=20 mg/kg/day Developmental LOAEL=80 mg/kg/day ( HDT

- 10% decrease in body weight compared to controls, not statistically significant) Abortions were increased at 80 mg/kg/day. Teratogenicity was not observed. 870.3800 2

- Generation Repro duction, Rat 40245515 0, 25, 250, and 1000
ppm M:F 1.9/2

. 2, 19/21, or 75/88 mg/kg/day Parental NOAEL=25 ppm (2 mg/kg/day) Parental LOAEL=250 ppm (21 mg/kg/day)

- decreased body weight gain in F1a adult females Reproductive NOAEL=25 ppm (2.5 mg/kg/day) Reproductive LOAEL=250 ppm (25 mg/kg/day)

- decreased body weight gain during lactation for F1b and F2b pups Offspring NOAEL= 25 ppm (2.5 mg/kg/day) Offspring LOAEL= 250 ppm (25 mg/kg/day)

- decreased absolute splenic weights. 870.4100b Chronic Fe eding, Dog 40245512 0, 25, 250, and 1500
ppm M:F: 0,0, 0.79/0.90, 8.16/8.18, or 51.46/52.02 mg/kg/day. NOAEL (M) = 25 ppm (0.79 mg/kg/day) NOAEL (F) = 250 ppm (8.16 mg/kg/day) LOAEL (M) = 250 ppm (8.18 mg/kg/day)

- elevated serum bilirubin, AST, and urinary volume, reduced body weight gain (20%). LOAEL (F) = 1500 ppm (52.02 mg/kg/day)

- increased serum creatinine, bilirubin, AST, and globulin, decreased body weight gain of 18.2% 870.4200b Carcinogenicity, M ouse 40245513 0, 20, 200, or 1500 ppm M:F: 0/0, 2.5/3.1, 25/31 and 197/247 mg/kg/day. NOAEL =20 ppm (3 mg/kg/day) M LOAEL = 200 ppm (30 mg/kg/day)

- bilateral seminiferous degeneration and oligospermia. Although frank toxicity was not observed in the

### Page 27 of 36 Table A.2.2. Subchronic, chronic, and Other Toxicology Profile for Tribenuron Methyl
Guide line Study Title MRID Dose Levels Results

females, HED peer review judged the dose levels to be adequate. There was no evidence of carcinogenicity. 870.4300 Chronic Feeding/Carcinogenicit y, Rat 40245511 0, 25, 250 or 1250 ppm 0/0, 0.95/1.2, 10/13 and 55/76 mg/kg/day. NOAEL=25 ppm(0.95/1.2 mg/ kg/day, M/F) LOAEL=250 ppm (10/13 mg/kg/day, M/F)

- decreased body weight gain in both sexes. Statistically significant increase in mammary gland adenocarcinomas in female rats at 1250 ppm (76 mg/kg/day, HDT) 870.4300 Supplement

- Estrogenic Activity in Rats 41181901 0 and 390 mg/kg/day for 90 days Weak estrogenic activity was observed in female rats. The technical and 7 metabolites may be agonists for the estrogen receptor. 870.5100 Gene Mutation Bacterial Reverse Mutation Assay 00148641 Up to 500 μg/plate without metabolic activation Up to 2000 μg/plate with metabolic activation Negative.

870.5300 Gene Mutation in vitro Mammalian Cell (Chinese Hamster Ovary) 00149671 0.5 to 5.0 mM with/without metabolic activation Negative.

870.5395 Cytogenetics, Mouse Micronucleus Bone Marrow 00148644 5000 mg/kg/day Negative.

870.5395 Cytogenetics, Rat Micronucleus Bone Marrow 00148642 50, 500, 5000 mg/kg/day Negative.

870.5550 Other Effects

– Unscheduled DNA Rat Hepatocyte 00148643 0 to 2500μM Negative.

870.6200a Acute Oral Neurotoxicity Study

- Rats 48732501 0, 100, 300, and 1000 mg/kg/day NOAEL=300 mg/kg/day LOAEL = 1000 mg/kg/day, based on body weight changes (BW loss in males, decreased BWG in females), reduced food consumption, and/or food efficiency, and tra nsient effects on motor activity and rearing. 870.6200b Subchronic Oral Neurotoxicity Study

- Rats 48737601 0, 50, 200, or 700 ppm mg/kg/day M:F= 0/0, 2.8/3.2, 11.3/12.8, and 40.1/46.6. NOAEL= 200 ppm (equivalent to 11.3/12.8 mg/kg/day,). LOAEL= 700 ppm (equivalent to 40.1/46.6 mg/kg/day) based on decreased body weight and body weight gains, reduced food consumption, and food efficiency.

### Page 28 of 36 Table A.2.2. Subchronic, chronic, and Other Toxicology Profile for Tribenuron Methyl
Guide line Study Title MRID Dose Levels Results

870.7485 Metabolism Study

- Rat 40245516 Single: low

- 20 mg/kg/day; high

- 1700 to 2000 mg/kg/day Repeated: 100 ppm for 21 days followed by 20 mg/kg/day single dose. Single oral dose readily absorbed, low dose (20 mg/kg) single and repeated dose 26

- 33 hours (half

- life); single high dose (1700

- 2000 mg/kg) 51

- 54 hours in males and 69

- 96 hours in females. Major excretion via urine (2

- 4 x feces). Tissue levels increased with dose. No accumulation in any particular tissue. 870.7600 Dermal Penetration

- Rat 48625901 0.03, 0.3 and 3.0 mg/12

cm 2 (male) and 0.3 mg/12 cm 2 (female) Based on the anticipated duration of human worker exposure (8

- 10 hours a day), the DAF of 17.7% from the 0.03 mg/ 12 cm 2 dose level group (10 hours of exposure) is considered the most appropriate for risk assessment. 870.7800 28

- Day Immunotoxicity study in Rats 48641101 50, 150, 300, or 600 ppm (equivalent to 0, 3.8, 11, 23, and 44 mg/kg bw/day, respectively) NOAEL=300 ppm ( equivalent to 23 mg/kg bw/day);

LOAEL= 600 ppm (equivalent to 44 mg/kg bw/day) based on lower body weight, body weight gains, and food consumption when compared to the control.

Under conditions of this study, the immunotoxicity NOAEL is 600 ppm (equivalent to 44 mg/kg bw/day, the highest dose tested); the LOAEL was
not determined.

### Page 29 of 36 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 ethic s requirements

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

. Descriptions of data sources as well as guidance on their use can be found at : http://www.epa.gov/pesticides/science/handler

- exposure

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

- app

- exposure

- data.html

.

### Page 30 of 36 Appendix C

. Occupational Algorithms

Occupational Non

- cancer Handler Algorithms

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

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

E = e xposure (mg ai/day), UE = u nit e xposure (μg ai/l b 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 or gal/day ).

The daily doses are calculated using the following formula:

ADD= E * AF
BW where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day), E = e xposure (mg ai/day), AF = absorption fa ctor (dermal or inhalation), and BW = body weight (kg).

Margin of Exposure: Non

- cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal and/or inhalation dose s received by occupational handlers are compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occupational handlers for each exposure route

. All MOE values 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).

Occupational Non

- cancer Post

- application Algorithms

Potential daily exposures for occupational post

- application workers are calculated using the following formulas:

DFR t 

### =AR * F* (1

- D) t 

### * � 4.54E8 ug lb � * � 2.47E

- 8 A

cm 2 

### �

### Page 31 of 36 where:

DFR t 

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

### ), AR = a pplication r ate (lb ai/acre), F = fraction of ai retained on foliage or 25% (unitless), D = fraction of residue that dissipates daily or 10% (un itless), and
t = number of days after application day (days)

.

E=TC * DFR t 

### * ET * 0.001 mg
ug where: E = e xposure (mg ai/day), TC = t ransfer coefficient (cm 2 

### /hr), DFR t 

### = d islodgeable f oliar r esidue on day “t” (μg/cm 2 

### ), and ET = e xposure t ime (hours/day).

The daily doses are calculated using the following formula:

ADD= E * AF
BW where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day), E = e xposure (mg ai/day), AF = absorption fa ctor (dermal), and BW = body weight (kg).

Margin of Exposure: Non

- cancer risk estimates for each scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal dose received by occupational post

- application workers is compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occupational post

- application workers. All MOE values a re calculated using the following formula:

MOE= POD
ADD where:

MOE = margin of exposure: value used by HED to represent risk estimat es (unitless), POD = point of departure (mg/kg/day), and ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).

### Page 32 of 36 Appendix D

. Dietary Exposure/Risk Modeling Input and Output

US EPA Ver. 3.16, 03

- 08

- d
DEEM

- FCID Chronic analysis for TRIBENURON METHYL Residue file: Tribenuron methyl.R08 Adjust. #2 NOT used Analysis Date 07

- 30

- 2015 Residue file dated: 07

- 30

- 2015/10:22:46 Reference dose (RfD) = 0.008 mg/kg bw/day

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

Food Crop Residue Adj.Factors EPA Code Grp Food Name (ppm) #1 #2

---------- ---- ------------------------------- ---------- ------ ------ 1500025000 15 Barley, pearled barley 0.050000 1.000 1.000 1500025001 15 Barley, pearled barley

- babyfood 0.050000 1.000 1.000 1500026000 15 Barley, flour 0.050000 1.000 1.000 1500026001 15 Barley, flour

- babyfood 0.050000 1.000 1.000 1500027000 15 Barley, bran 0.050000 1.000 1.000 1500120000 15 Corn, field, flour 0.010000 1.000 1.000 1500120001 15 Corn, field, flour

- babyfood 0.010000 1.000 1.000 1500121000 15 Corn, field, meal 0.010000 1.000 1.000 1500121001 15 Corn, field, meal

- babyfood 0.010000 1.000 1.000 1500122000 15 Corn, field, bran 0.010000 1.000 1.000 1500123000 15 Corn, field, starch 0.010000 1.000 1.000 1500123001 15 Corn, field, starch

- babyfood 0.010000 1.000 1.000 1500124000 15 Corn, field, syrup 0.010000 1.000 1.000 1500124001 15 Corn, field, syrup

- babyfood 0.010000 1.000 1.000 150012500 0 15 Corn, field, oil 0.010000 1.000 1.000 1500125001 15 Corn, field, oil

- babyfood 0.010000 1.000 1.000 2003128000 20C Cottonseed, oil 0.020000 1.000 1.000 2003128001 20C Cot tonseed, oil

- babyfood 0.020000 1.000 1.000 2001163000 20A Flax seed, oil 0.020000 1.000 1.000 1500231000 15 Oat, bran 0.050000 1.000 1.000 1500232000 15 Oat, flour 0.050000 1.000 1.000 1500232001 15 Oat, flour

- babyfood 0.050000 1.000 1.000 1500233000 15 Oat, groats/rolled oats 0.050000 1.000 1.000 1500233001 15 Oat, groats/rolled oats

- babyfood 0.050000 1.000 1.000 2001319000 20A Rapeseed, oil 0.020000 1.000 1.000 2001319001 20A Rapeseed, oil

- babyfood 0.020000 1.000 1.000 1500323000 15 Rice, white 0.050000 1.000 1.000 1500323001 15 Rice, white

- babyfood 0.050000 1.000 1.000 1500324000 15 Rice, brown 0.050000 1.000 1.000 1500324001 15 Rice, brown

- babyfood 0.05 0000 1.000 1.000 1500325000 15 Rice, flour 0.050000 1.000 1.000 1500325001 15 Rice, flour

- babyfood 0.050000 1.000 1.000 1500326000 15 Rice, bran 0.050000 1.0 00 1.000 1500326001 15 Rice, bran

- babyfood 0.050000 1.000 1.000 1500344000 15 Sorghum, grain 0.050000 1.000 1.000 1500345000 15 Sorghum, syrup 0.050000 1.000 1. 000 0600347000 6 Soybean, seed 0.010000 1.000 1.000 0603348000 6C Soybean, flour 0.010000 1.000 1.000 0603348001 6C Soybean, flour

- babyfood 0.010000 1.000 1.000 060 0349000 6 Soybean, soy milk 0.010000 1.000 1.000 0600349001 6 Soybean, soy milk

- babyfood or in 0.010000 1.000 1.000 0600350000 6 Soybean, oil 0.010000 1.000 1.000 0600350001 6 Soybean, oil

- babyfood 0.010000 1.000 1.000 1500381000 15 Triticale, flour 0.050000 1.000 1.000 1500381001 15 Triticale, flour

- babyfood 0.050000 1.000 1.000 8601000000 86A Water, direct, all sources 0.035000 1.000 0.657 8602000000 86B Water, indirect, all sources 0.035000 1.000 0.657 1500401000 15 Wheat, grain 0.050000 1.000 1.000 1500401001 15 Wheat, grain

- baby food 0.050000 1.000 1.000 1500402000 15 Wheat, flour 0.050000 1.000 1.000 1500402001 15 Wheat, flour

- babyfood 0.050000 1.000 1.000 1500403000 15 Wheat, germ 0.050000 1.000 1.000 1500404000 15 Wheat, bran 0.050000 1.000 1.000

### Page 33 of 36 US EPA Ver. 3.18, 03

- 08

- d
DEEM

- FCID ACUTE Analysis for TRIBENURON METHYL NHANES 2003

- 2008 2

- Day Residue file: Tribenuron methyl.R08 Adjustment factor #2 NOT used. Analysis Date: 07

- 30

- 2015/10:26:07 Residue file dated: 07

- 30

- 2015/10:22:46 RAC/FF intake summed over 2 4 hours Run Comment: ""

=============================================================================== Summary calculations

-- per capita: 95th Percentile 99th Percentile 99.9th Percentile Exposure % aRfD Exposure % aRfD Exposure % aRfD

---------- -------- ---------- -------- ---------- -------- Total US Population: 0.002097 0.07 0.003365 0.11 0.006232 0.21 All Infants: 0 .006201 0.21 0.008184 0.27 0.011901 0.40 Children 1

- 2: 0.003313 0.11 0.005022 0.17 0.011356 0.38 Children 3

- 5: 0.002719 0.09 0.003970 0.13 0.006338 0.21 Childr en 6

- 12: 0.002126 0.07 0.003248 0.11 0.004864 0.16 Youth 13

- 19: 0.001736 0.06 0.002771 0.09 0.004219 0.14 Adults 20

- 49: 0.001993 0.07 0.002879 0.10 0.004155 0.14 Adults 50

- 99: 0.001773 0.06 0.002696 0.09 0.004025 0.13 Female 13

- 49: 0.002033 0.07 0.002886 0.10 0.00 4016 0.13

US EPA Ver. 3.16, 03

- 08

- d
DEEM

- FCID Chronic analysis for TRIBENURON METHYL NHANES 2003

- 2008 2

- day Residue file name: Tribenuron methyl.R08 Adjustment factor #2 used. Analysis Date 07

- 30

- 2015/10:23:43 Residue file dated: 07

- 30

- 2015/10:22:46 Reference dose (RfD, Chronic) = .008 mg/kg bw/day

=============================================================================== Total exposure by population subgroup

------------------------------------------------------------------------------- Total Exposure

----------- ------------------------ Population mg/kg Percent of

Subgroup body wt/day Rfd

-------------------------------------- ------------- ---------------- Total US Population 0.000607 7.6% Hispanic 0.000594 7.4%
Non

- Hisp

- White 0.000618 7.7%
Non

- Hisp

- Black 0.000515 6.4%
Non

- Hisp

- Other 0.000708 8.9% Nursing Infants 0.000534 6.7%
Non

- Nursing Infants 0.001797 22.5% Female 13+ PREG 0.000556 7.0% Children 1

- 6 0.000911 11.4% Children 7

- 12 0.000594 7.4% Male 13

- 19 0.000466 5.8% Female 13

- 19/NP 0.000483 6.0% Male 20+ 0.000560 7.0% Female 20+/NP 0.000590 7.4% Seniors 55+ 0.000544 6.8% All Infants 0.001407 17.6% Female 13

- 50 0.000575 7.2% Children 1

- 2 0.001003 12.5% Children 3

- 5 0.000874 10.9% Children 6

- 12 0.000627 7.8% Youth 13

- 19 0.000475 5.9% Adults 20

- 49 0.000589 7.4% Adults 50

- 99 0.000557 7.0% Female 13

- 49 0.000575 7.2%

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

### Page 34 of 36 Appendix E. Nomenclature and Physical/Chemical Properties

TABLE E.1 T ribenuron m ethyl Nomenclature Chemical structure

Common name Tribenuron methyl Molecular formula C 15 H 1 7 N 5 O 6 S Molecular weight 395.4 CAS name Methyl

- 2

- [[[[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)methylamino] carbonyl]amino]sulfonyl]benzoate IUPAC name Methyl

- 2

- [4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl(methyl)carbamoyl

sulfamoyl]benzoate CAS registry number 101200

- 48

- 0

TABLE E.2 Physicochemical Properties of the Technical Grade Tribenuron M ethyl

Parameter Value Reference Melting point/range (oC) 1 41 EPA Pesticide Fact Sheet Number 219: Tribenuron methyl pH 4. 27 Density (g/cm 3 ) 1.5 4 Water solubility (g/L at 2 0 oC) pH 5 0. 049 pH 7 2.04 pH 9 18.3 Solvent solubility (g/L at 25oC) Acetone

- 0.044 Acetonitrile

- 0.054 Carbon tetrachloride

- 0.003 Ethyl acetate

- 0.0175 Hexane

- <0. 00 1 Methanol

- 0.0034 Vapor pressure (25oC) 5.3 x 10

- 8 Pa ( 4 x 10

- 10 mm Hg) Dissociation constant (pK a ) 4.7 Octanol/water partition coefficient (Log [K OW ]) pH 7 0. 3

### Page 35 of 36 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 directly contact

. Sprays can also deposit on surfaces where individuals come into contact wi th 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 pr emise 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 them 12



### . [ Direct exposures would include inhalation of the spr ay 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 expos ure to deposited residues has been completed to address drift from the agricultural applications of tribenuron

. In the spray drift scenario, the deposited residue value was determined based on the amount of spray drift that may occur at varying distances f rom 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 available 13 14



### . AgDrift is appropriate for use only when applications are made by aircraft, airblast orchard sprayers, and groundboom sprayers

. When AgDrift was deve loped, 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

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

13 http://www.agdrift.com/

14 Note that for many cases the scenarios outl ined in the screening approach represent actual use practice so risk assessors should be aware and characterize these appropriately.

### Page 36 of 36 not typically applied to tree canopies) or specific labe l prohibitions (e.g., aerial applications are not allowed)

. Section 6.1 .1 provides the screening level drift related risk estimates.

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

. In order to account for this issue and to provide additional risk management options additional spray drift deposition fractions were also considered

. These drift estimates represent plausible options for pesticide labels

.