UNITED STATES ENVIRONMENTAL PROTECT I ON A GENCY

WASH I NGTON. D.C. 20460

OFFI CE OF C H E MI CA L SAFE TY A ND POLLUTION PREVENTION



### MEMORANDUM

Date: 15 Septe mber 2015

SUBJECT: T hifen s ulfuron Methyl. Dr aft Hwnan Health Ri sk Assess m e nt in S upp ort of R egistration R eview.

P C Co d e : 128845 D ec i s ion No.: 492903 Petition No.: NA DP Bar co d e: 0 421391 Registration No.: NA Case No.: 7206 Ri s k Assess m ent Type : S i ngle C hemical Aggregate Regulatory Ac tion: Regi st rati o n Re view T X R No. : NA CAS No.: 79277-27-3 MRID No.: None 40 CFR: 180.439



### FROM : Michael A. Doherty
, Ph .D.
, Chemist 

# fo**J~ ~~** 

Z

. aida Figueroa
, DrPH
, Indu stria l

### ygi**,~ni** 47

### ~**~** \L--_ Karlyn Middleton
, M.S

. , Tox i co l og i s t

### 'L~ Risk Assessme n t Bran c h II

- 

# -··zt-

--- -.__ Health Effec t s Di vision (7509P)



### THROUGH: Christ i n a Swartz
, Bran c h Chief

# ~_A­ Risk Assess m e nt Branch II Health Effects Division (7509 P )



### TO : Bri ttany Pru i tt, Che m ica l R ev i ew Manag e r K elly Sherman, Bran c h Chief Risk Management and Impl ementation Branch 

### 3 (RMIB 3) Pestic id e Re

- Evaluation Di v ision (7508P)

As part of registration review, H E D has exa min ed the toxico l og i ca l and expos ur e d ata b ases fo r assessing human health risks associated with thifensulfuron methyl and cond u c t ed a new risk
assessment fo ll owing current practic es and policie s

. S i gnificant changes r e l ative to the l ast ri sk
assessment (D391088, W. Drew
, 2012) includ e :

• Establishment of e ndpoint s and points of departure fo r assessing d e rmal and incidental

ora l exposure for ch ild ren;

• Assess ment of spray dr i ft risk for adu l t s and child r en.

Pag e 1 of 37T ab l e of Co nt ents

1.0
2

. 0 2.1 2.2
3.0 3.1 3.2 

### 3.3
4.0 4

. 1 4.2 4.3 4.4
5.0 5. 1 5.2 5.3 Exec utiv e S ummar y

.. . . .. . . ........ . .. .. .. . ... ... . . . ... ...... .... .. ... .. .. .. ... ..... ... .. ..... ... .... .... ... .. . .. .. . .. . ..... .. .. 3
H E D Re comme nd at i ons

................................... .. .................................................................. 4 To l erance Co n s id e r a ti o n s

.. . ... .. ... .. .... .... ..... . . . ... ... ...... . . ... .. . ... .. ..... ... . ...... ..... .. ... . ..... . ... ... .... 4 L abe l Co n s id e rati ons

....................................................................................................... 5
I n t r oduction

...................................... ... ............. .. .... .. ...... .. ..... ... ...... . ...... . ............. .... ............. 5 C h em i ca l Id ent it y and Ph ys ic al/C h e mic a l C h aracte ri st i cs

.. .. ...... .. ..... .. ............... .. .. .... ..... 5 Pe st icid e Use P atte rn and A nt ic i pated Exposure P athways

............................................. 5 Consideration of Env ir onmenta l Ju st ic e

... ... ........ . ... ... ...... . . ...... .. ..... . ............................... 8
Hazard Id en tifi cat i on/Tox ic o l ogy

. .... . . . . .. ... ... . . .. . ........ .. . . ..... . . . ....... . ... .. ..... ..... . .. .. ......... ......... 9 S umm ary of Toxicological Effects

.. .. . .. ..... .. ... ...... ... ... ...... . ... ..... ...................................... 9 Safety Factor fo r I nfants a nd Chi ldr en (FQ P A Safe t y Facto r )

............................... .. ...... 1 0 Toxicity Endpoint and Point of Dep artu r e Se l ec ti o n s

.. .. ...... ...... ...... .. ..................... .. ..... 10 Endoc rin e Disruptor Screeni n g Program

.. ... ...... .... ........... . ....... .. .... ..... ... .... .. ..... . .. . .. ..... . 12 Dietary Exposure a nd Risk Assessme nt

... ... .. ........ . .... . ........ .. ..... .. ...... .. ..... .. . .. .. ..... . ..... ..... . 1 3 Water Residue Profil e

.. ....... ... .. ....... .... . . ... . . . ... .... .. ... . . ... ... . .. ...... . . .. ... .. .. .. . .. ...... . ..... .. .... .... 13 F ood Residue Profile

............................ . .............. ... ........................................................ 1 3 Di etary Exposu r e and Ri s k Es timat es

.. .............. .. ... ....... . ... . .. ... .... .... ..... .. ..... ... ....... . ...... . 1 4
6. 0 R es id e nt i a l (No n-O cc upational) Ex po su re / Risk C h aracte ri za ti on

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

.......................................................... . ........ . ....... . .......................................... 1 4 6 .1. 1 Comb i ned Ri sk Esti m a t es from Lawn Deposition Adjacent to Ap plicati o n s

. . .. . .. ....... 15 6.2 R es idential Bysta nd er Post-Application Inhalation E xposu r e

.. ..... ... ........... . ......... . ....... 16
7 .0 Agg r egate Exposure/Risk C h aracter i zation

... ... .... ..... .... ... .... .... .... ... ..... .. .. . . ... .. .... .... ..... ... .. 1 6
8.0 C um u l at i ve Exposure/Risk C h aracter i zat i o n

.................................................................... . 16
9.0 Occupational Ex po s ure / Ris k Characterization

.... ....... . ... ... ............. .. ...... ............ . .............. 17 9. 1 Occupational H andler Exposure / Risk Estimates

.............................................. . ............. 17 9

. 2 Occupational P ost-app li cat i o n Exposure / Risk Es t i mates

. . .. .. . .. . . ... ..... ... ............ . ..... .... . . 20 9.2. 1 Occupational P os t

- a ppli ca tion Inh a lati o n Exposure/R i sk Estimates

........................... 20 9.2.2 Occupational P ost

- applicat i on Dermal E xposu r e / Ri sk Esti mat es

............................... 20
l 0.0 Public H ea lth an d Pesticide Ep id em i o l ogy D a t a

.......... . ....... . ...................... . ..................... 23
11 .0 L iter a tur e Ref e r ences

...... . . ....... . .. .. .. . ...... ....... . ........... ... .. ....... . ....... . .... .. . . .. .... . .. .. . . . ..... . ........ 24
1 2.0 R efe r e n ces

.......................................................................................................................... 24 Appe n dix A. Toxicology D ata Requirements and Tox ic o l ogy Profil e

..................................... 25 Appendix B. R ev i ew of Human R esearc h

.. .. . . . ....... ... .. . . . .... ..... .. . . ....... .. .. . .. .. ..... . . ........ . ..... . . ..... . 29 Appendix C. Occ upational A l go rithm s

...... .. ... .. . . . ...... .. . . .. .. ...... ... .. ...... . ............ ... ....... .. .... . . ...... 30 Ap p e nd i x D. Dietary Ex po sure/Risk Model in g Input and Output

........................... . .............. . 33 Appendix E. No m enclature and Ph ysical / Chemica l P roperties

............................................... 35 Appendix F. Sp r ay Dri ft Detailed D esc ripti o n

.......................... .. ..... ... ..... ..... ... ........... .... ......... 36

P age 2 of 37

### Page 3 of 37

1 .0 Executive Summary

Thifensulfuron m ethyl ( methyl

- 3

- [[[[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino] carbonyl]amino]sulfonyl] thiophene

- 2

- carboxylate) is a sulfonylurea herbicide (Group 2) that acts through inhibition of the enzyme acetolactate synthase (ALS), affecting cell division and growth in plants

. It is registered for postemergence application to barley, canola
, chicory
, cotton, flax, field corn, oats, safflower, soybeans, and wheat for selective control of broadleaf weeds

. It is also registered for use as a preemergence burn

- down broadcast application for barley, field corn, oats, soybeans, and wheat, and as a preplant burn

- down application for canola, cotton, rice, grain sorghum, a nd sugar beets.

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

. Thifensulfuron methyl is formulated as a dry flowable (DF) and as soluble granules (SG)

. It is applied using common agricultural equipment (i.e., aerial, ground, and chemigation)

. Exposure to residues of thifensulfuron methyl may occur via the diet due to its use on food and feed crops. Exposures in a residential setting (i.e., non

- dietary e xposures) are not expected.

A hu man health scoping document for thifensulfuron methyl was completed in 201 1 ( D 3 83624
, D. Dotson ) . Identified data needs include d a cute and subchronic neurotoxicity studies in the rat, an immunotoxicity study, a 21

- or 28

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

- day subchronic inhalation study



### . At this time, all of the required studies have been submitted or waived
, and both the toxicology and exposure database s for thifensulfuron methyl are considere d complete and adequate for risk assessment

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

. 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 thifensulfuron methyl using tolerance

- level residues in foods and a sulfonylurea

class

- wide screening

- level estimate of residues in drinking water

. The acute d ietary risk estimate (females of child

- bearing age only) is 3% of the acute population

- adjusted dose (PAD), and the chronic dietary risk estimates (al l population groups) range from 18 to 6 3% of the chronic PAD; all dietary risk estimates are not of concern

.

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

. Therefo re, a quantitative residential exposure assessment was not performed

. However, thifensulfuron methyl can be applied via groundboom and aerial equipment and there is the potential for indirect exposure to residues as a result of spray drift

. Therefore , HED estimated risks associated with spray drift. The resulting ris k estimates are not of concern ( margin s of exposure (MOE s) ≥ 1,300 with a level of concern (LOC) of 100)

.

Since there are n o residential exposure pathways for thifensulfuron methyl , the aggregate exposure and risk estimates are equivalent to the dietary exposure and risk estimates and do not exceed HED’s level of concern.

### Page 4 of 37

No chemical

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

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

. All occupational handler scenarios for the registered uses resulted in MOEs greater than the LOC of 100 at some level of personal protective equipment (PPE) risk mitigation (i.e., anywhere from baseline attire with no chemical

resistant gloves and no respirator to engineering control s ) and are not of concern

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

- cancer occupational post

- application inhalation exposure assessment was not performed for thifensulfuron methyl

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

. Post

application dermal exposure and risk estimates for the registered agricultural uses resulted in MOEs greater than 100 and are not of concern on d ay 0 (i.e., 12 hours following application)

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

acu te toxicity of thifensulfuron methyl and is adequate to protect agricultural workers from post

application ex posures

.

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

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

2.0 HED Recommendations

2.1 Tolerance Considerations

The residue definition for tolerance enforcement is thifensulfuron methyl only. The existing tolerances (40 CFR 180. 4 3 9 ) are supported by the available residue chemistry data

. At this time, there are Canadian maximum residue levels ( MRL s ) for residues of thifensulfuron methyl in barley, oats, and wheat at 0.05 ppm ; flaxseed and rapeseed at 0.02 ppm; and dry soybeans at 0.1 ppm. T here are no Codex MRLs for th i fensu l furon methyl at this time . The U.S. tolerance s for residues of thifensulfuron methyl are harmonized with Canada. No revisions to the existing U.S. tolerances are needed during registration review.

An analytical reference standard for thifensulfuron methyl is currently available in EPA’s National Pes ticide Standards Repository (NPSR) and has an expiration date of 19 February 2019 (email communication between G. Verdin and J. Van Alstine, 5/11/2015)

. The registrant is required to maintain reasonable amounts of the reference standards for thifensulfuron methyl in the NPSR as long as tolerances remain published in 40 CFR §180. 439

. When necessary, new reference standards, or updated certificates of analysis (COAs), should be sent to the Analytical Chemistry Branch (ACB), which is located at Fort Meade, MD

. It should be sent to the attention of either Theresa Cole or Thuy Nguyen at the address listed below, along with a letter of transmittal

. Please note that the full 9

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

.

USEPA

National Pesticide Standards Repository

### Page 5 of 37 Analytical Chemistry Branch/BEAD/OPP 701 Mapes Road Fort Geor ge G. Meade, MD 20755

- 5350

The letter of transmittal should include the assay of the standard, name of the analytical method used, a statement of principal impurities, purification procedures employed, storage requirements, and special precautions for sa fe 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 specifi ed by the Occupational Safety and Health Administration (OSHA) in 29CFR §1910.1200

.

2.2 La bel C onsiderations

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

.

3.0 Introduction

3.1 Chemical Identity and Physical/Chemical Characteristics

Thifensulfuron m ethyl ( methyl

- 3

- [[[[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino] carbonyl]amino]sulfonyl] thiophene

- 2

- carboxylate) is a sulfonylurea herbicide (Group 2)

. The chemical properties of thifensulfuron methyl do not suggest that there are any particular exposure issues that warrant special consideration

. The compound has a dissociation constant of 4. 0 at 25°C , making its water solubility dependent on pH, with low solubility below pH 3

. The potential for thifensulfuron methyl to partition into fatty matrices is also, by extension, pH dependent; however, based on the octanol/water partitioning coefficients, such partitioning is unlikely to occur at physiological pH levels

. Thifensulfuron methyl has a relati vely low vapor pressure , indicating that inhalation of vapors is unlikely to be a significant source of exposure under ambient conditions

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

.

3.2 Pesticide Use Pattern and Anticipated Exposure Pathways

Thifensulfuron methyl is registered for postemergence application to barley, canola
, chicory
, cotton, flax, field corn, oats, safflower, soybeans, and wheat for selective control of broadleaf weeds

. It is als o registered for use as a preemergence burn

- down broadcast application for wheat, barley, oats, soybeans, and field corn, and as a preplant burn

- down application for canola, cotton, rice, grain sorghum, peanuts, and sugar beets. In addition to these crop u ses, it is also registered for use on agricultural fallow, idle and conservation reserve land

. Thifensulfuron methyl is formulated as dry

- flowable (DF) and soluble

- granul ar (SG) end

- use products. There are 4 activ ely registered technical products and 48 active ly registered end

- use products , and they are typically applied as preplant or postharvest burn

- down , pre

- emergence , or post

- emergence broadcast applications using common agricultural ground or aerial equipment.

### Page 6 of 37

The registered use pattern s allows on e or two application per season ; therefore , the duration of exposure for occupational handlers is expected to be short

- term ( i.e

. , 1 to 30 days) and i ntermediate

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

- term exposures (greater than 6 months) are not anticipated

. The PPE statement s on registered labels require applicators, flaggers and other handlers to wear the following : long

- sleeved shirt, long pants, 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 Thifensulfuron 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

Barley, Wheat Between 2

- leaf and flag

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

[ 352

- 446, 352

- 538, 352

- 610, 352

- 611, 352

- 617, 352

- 633, 352

- 641, 352

- 661, 352

- 714, 352

- 715, 352

- 751, 352

- 876, 352

- 896, 352

- 897, 352

- 899 ] 0.0019

-

0.0 28 1 0.0 4 7 45

- day PHI for grain 7

- day feeding restriction for forage 30

- day feeding restriction for hay

Triticale Between 2

- leaf and flag

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

[ 352

- 446, 352

- 610, 352

- 611, 352

- 617, 352

- 633, 352

- 641, 352

- 661, 352

- 714, 352

- 715, 352

- 751, 352

- 876 ] 0.0019

-

0.028 2 0.04 7 45

- day PHI for grain 7

- day feeding restriction for forage 30

- day feeding restriction for hay

Soybean Preplant or after first trifoliate is fully expanded Broadcast by ground boom or aerial DF, DG, SG

[ 352

- 446, 352

- 573, 352

- 574, 352

- 599, 352

- 611, 352

- 633, 352

- 661, 352

- 756, 352

- 757, 352

- 853 ] 0.0016

-

0.023 2 0.023 45

- day PHI for grain 7

- day feeding restriction for forage 30

- day feed ing restriction for hay

Rice Preplant Broadcast by ground boom or aerial DF, SG

[352

- 611, 352

- 853] 0.0094

-

0.02 1 1 0 .021 45

- day PHI for grain 7

- day feeding restriction for forage 30

- day feeding restriction for hay Canola , Sugar Beet 60 days preplant Broadcast by ground boom or aerial DF

[352

- 611] 0.0094

-

0.01 9 NS 0.031

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

- Evaluation Division. It has not undergone review by the Biological and Economic Analysis Division for completeness or accuracy.

### Page 7 of 37

Table 3.2

. Summary of Directions for Registered Uses of Thifensulfuron 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

Field Corn Preplant through 6

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

[ 352

- 446, 352

- 571, 352

- 611, 352

- 633, 352

- 667, 352

- 721, 352

- 759, 352

- 777, 352

- 854 ] 0.0016

-

0.01 9 2 0 .019 45

- day PHI for grain 7

- day feeding restriction for forage 30

- day feeding restriction for hay

Oats , Sorghum 2

- 3 leaf stage Broadcast by ground boom, aerial, or chemigation DF, DG, SG, OD

[ 352

- 446, 352

- 538, 352

- 611, 352

- 617, 352

- 633, 352

- 641, 352

- 661, 352

- 714, 352

- 876, 352

- 897, 352

- 899 ] 0.0094

-

0.0 28 1 0.0 4 7 45

- day PHI for grain 7

- day feeding restriction for forage 30

- day feeding restriction for hay

Safflower Postemergence Broadcast by ground boom or aerial SG

[ 352

- 633 ] 0141

-

0.01 9 2 0.01 9 PHI = 81 days

Peanut Preplant ≥ 45 days prior to planting Broadcast by ground boom or aerial SG

[352

- 853] 0.01 6 1 0 .016

Cotton 14 days prior to planting Broadcast by ground boom or aerial DF

[352

- 611
, 352

- 446 ] 0.0094

-

0.016 1 0 .01 6

Chickory 2 true

- leaf stage Broadcast by ground boom or aerial SG

[352

- 854] 0.0025

-

0.005 2 0.005

Preplant Burn

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

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

[ 352

- 446, 352

- 538, 352

- 611, 352

- 617, 352

- 633, 352

- 641, 352

- 648, 352

- 650, 352

- 661, 352

- 714, 352

- 749, 352

- 755, 352

- 777, 352

- 843, 352

- 853, 352

- 876, 352

- 877, 352

- 889, 352

- 899 ] 0.0016

-

0.0 2 8 3 0.04 7 Preplant burn

- down After application, allow at least : 14 days before planting
cotton , 60 days befor e planting sugar beet and canola
, 45 days before planting other crops

.

### Page 8 of 37

Table 3.2

. Summary of Directions for Registered Uses of Thifensulfuron 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

Fallow, I dle, Conservation Reserve L and † Spring

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

[ 352

- 446, 352

- 538, 352

- 610, 352

- 611, 352

- 617, 352

- 633, 352

- 641, 352

- 661, 352

- 714, 352

- 715, 352

- 751, 352

- 759, 352

- 777, 352

- 854, 352

- 899 ] 0.0031

-

0.0 2 8 3 0.04 7 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
cotton , 60 days before planting sugar beet and canola
, 45 days before planting other crops

. † Based on information received by BEAD, the thifensulfuron methyl registrations are for use on fallow land . The conservation reserve program (CRP) for thifensulfuron methyl is not active ; however the use on CRP was assessed in this document

. There have been no forestry use s of thifensulfuron methyl based on the data available from the US Forest Service (2004) and the Bureau of Land Management (2002

- 2011)

. 

### Exposure Pathways

Individ uals may be exposed to thifensulfuron methyl via their diet (food and drinking water)

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

- dietary (i.e., residential) exposures

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

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

- application activities (dermal route)

.

3.3 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 1 2898, "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 o n patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting

. Extensive data on food consumption patterns are compiled by the USDA under the National Health and Nutritio n Examination Surveys/What We Eat in America (NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group

. Additionally, OPP is abl e to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant

. Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associated risks for adu lt applicators and for toddlers, youths, and adults entering or playing on treated areas

### Page 9 of 37

post

- application are evaluated

. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized soft ware and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Identification/Toxicology

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

. The last risk assessment for thifensulfuron methyl was conducted in 2012 ( D 391088; W. Drew). In 2011, a scoping document ( D 383624; W. Drew) was completed which outlined data gaps for several toxicity studies a s required in accordance with the current Part 158 Guidelines (40 CFR Part 158)

. The studies included dermal and inhalation toxicity, immunotoxicity
, and acute and subchronic neurotoxicity studies

. However, t he Hazard and Science Policy Council (HASPOC) de termined that the dermal and inhalation toxicity studies are not required at this time (TXR# 0054114) and t he immunotoxicity and neurotoxicity studies have since been submitted and reviewed

. The toxicological endpoints and points of departure (PODs) have been evaluated considering the new toxicology data; however, the new studies do not impact the current risk
assessment

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

. See Appendix A for the thifensulf uron methyl toxicology profile.

4.1 Summary of Toxicological Effects

Most findings in the submitted studies for thifensulfuron methyl were related to de creases in body weights, body weight gains, or organ weights (adrenal, spleen, and thyroid)

. There we re no gross or histopathological changes reported in any of the studies

. There was also no evidence of neurotoxicity or immunotoxicity seen in rat neurotoxicity and immunotoxicity studies

. Additionally, no evidence of carcinogenicity was observed in the mo use or rat carcinogenicity studies

. There was no indication of mutagenicity in the battery of available studies. Thifensulfuron methyl is classified as “not likely to be carcinogenic to humans.”

Increased quantitative susceptibility was seen in the rat developmental toxicity study

. Decreased fetal body weights, and an increased incidence of small renal papillae were observed in fetuses in the absence of maternal toxicity

. No evidence of increased susceptibility was seen in the rabbit developmental or ra t reproduction toxicity studies.

In acute lethality studies, thifensulfuron methyl has low or minimal acute toxicity via the oral (category IV), dermal (category III), and inhalation (category III ) routes of exposure

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

Thifensulfuron methyl is rapidly excreted in the urine and feces within 72 hours, with almost no
t issue or carcass accumulation; most was parent , with five minor metabo lites identified

. T he urine was the primary route of excretion. P arent thifensulfuron methyl , at up to 70% of the total dose
, accounted for the majority of the excreted radioactivity in the urine

. Minor metabolites were also present at low levels (<3%)

. Th e fecal metabolite profile was similar to that for urine

. Parent thifensulfuron methyl was predominant ly seen in feces (up to 17.8%) with the metabolites

### Page 10 of 37

being present in approximately the same percentage s as w ere reported in urine

. None of the metabolites exceeded 5% of the administered dose

. There were no major sex differences regarding any aspects of metabolism

.

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

HED recommends that the Food Quality Protection Act Safety Factor ( FQPA SF ) be reduced to 1 x for thifensulfuron methyl

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

- and/or postnatal toxicity , and no concern for neurotoxicity

. Although increased quantitative susceptibili ty was seen in the rat developmental study, concern is low since 1) no developmental effects were seen in the rabbit developmental or rat reproduction studies, 2) there are clear NOAELs/LOAELs for the fetal effects observed in the rat developmental study, and 3) the endpoints and points of departure selected for risk assessment are protective of the effects observed in the study

.

4.3 Toxicity Endpoint and Point of Departure Selections

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

re

- evaluated considering new toxicology data ; h owever, the new data do not alter the PODs previously selected

. However, in order to evaluate non

- occupational expo sures from spray drift, incidental oral and dermal POD s w ere selected from the thifensulfuron methyl database

. The acute dietary risk assessment is for females of child

- bearing age only, and it is currently based on decreased body weight and increased incidence of small renal papillae

. The endpoint was previously selected to be protective of the developing fetus since the effect was observed in the absence of maternal toxicity

. It should be noted that this approach is considered very conservative; howev er, HED did not update/change the existing acute dietary endpoint for the draft risk assessment. Also, the endpoints and POD s presented in the toxicology profile table (Appendix A ) have not been updated to comply with current policy regarding what constitu tes an adverse effect. The NOAELs and LOAELS have not been changed

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

. The PODs selected for risk assessment are protective of the effects observed in the thifensulfuron methyl d atabase

. A summary of toxicological doses and endpoints used in the thifensulfuron methyl human health risk assessments is presented below:

Table 4.3.1

. Summary of Thifensulfuron Methyl Doses and Endpoints for Use in Dietary and Non

Occupational Risk Assessments

. Exposure/ Scenario Point of Departure Uncertainty/ FQPA Safety Factors LOC for Risk

Assessment Study and Toxicological Effects

Acute dietary (females 13

- 49 only) NOAEL = 159

mg/kg/day UF A = 10X UF H = 10X FQPA SF = 1 aRfD = 1.59

mg/kg/day aPAD = 1.59 mg/kg/day Developmental oral toxicity in

rats

. LOAEL = 725 mg/kg/day, based on decreased mean body weight, and increased incidence of small renal papillae

.

### Page 11 of 37

Table 4.3.1

. Summary of Thifensulfuron Methyl Doses and Endpoints for Use in Dietary and Non

Occupational Risk Assessments

. Exposure/ Scenario Point of Departure Uncertainty/ FQPA Safety Factors LOC for Risk

Assessment Study and Toxicological Effects

Chronic dietary (all populations) NOAEL = 4.3

mg/kg/day UF A = 10X UF H = 10X FQPA SF = 1 cRfD = 0.043

mg/kg/day cPAD = 0.043 mg/kg/day Carcinogenicity oral toxicity in

mice

. LOAEL = 128 mg/kg/day, based on decreased body weight and body weight gain

. Incidental oral (short

- term) NOAEL = 7 mg/kg/day UF A = 10X UF H = 10X FQPA SF = 1 MOE = 100 90

- Day Oral Toxicity in Rats. LOAEL = 177 mg/kg/day based on decreased body weight and body weight gain in males and females and decreased spleen weights in males. Dermal short

- (1

- 30 days) and intermediate

term (1

- 6 months) NOAEL = 7 mg/kg/day

(default DAF of 100%) UF A = 10X UF H = 10X FQPA SF = 1 MOE = 100 90

- Day Oral Toxicity in Rats. LOAEL = 177 mg/kg/day based on decreased body weight and body weight gain in males and females and decreased spleen weights in males. Cancer (oral) Not likely to be a human carcinogen, based on the lack of evidence of carcinogenicity in rats

and mice. Point of Departure (POD) = a data point or estimated point derived from observed dose

- response data, which is used to mark the beginning of extrapolation t o determine risk associated with lower environmentally relevant human exposures

. UF = Uncertainty Factor

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

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

- species)

. FQPA SF = FQPA Safety Factor

. NOAEL = No Observed Adverse Effect Level

. LOAEL = Lowest Observed Adverse Effect Level

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

. RfD = Reference Dose

.

Table 4.3.2

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

Assessments. Exposure/ Scenario Point of Departure Uncertainty / FQPA Safety Factors LOC for Risk

Assessment Study and Toxicological Effects

Dermal short

- (1

- 30 days) and intermediate

term (1

- 6 months) NOAEL = 7 mg/kg/day

(default DAF of 100%) UF A = 10X UF H = 10X MOE = 100 90

- Day Oral Toxicity in Rats. LOAEL = 177 mg/kg/day based on decreased body weight and body weight gain in males and females and decreased spleen weights in males. Inhalation short

- (1

- 30 days) and intermediate

term (1

- 6 months) NOAEL = 7 mg/kg/day UF A = 10X UF H = 10X MOE = 100 90

- Day Oral Toxicity in Rats. LOAEL = 177 mg/kg/day based on decreased b ody weight and body weight gain in males and females and decreased spleen weights in males. Point of Departure (POD) = a data point or estimated point derived from observed dose

- response data, which is used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures

. UF = Uncertainty Factor

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

. UF H = potential

### Page 12 of 37

variation in sensitivity among members of the human population (intra

- species)

. FQPA SF = FQPA Safety Factor

. NOAEL = No Observed Adverse Effect Level

. LOAEL = Lowest Observed Adverse Effect Level

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

. MOE = Margin Of Exposure

. LOC = Level Of Concern

.



### 4 .4 Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals

. Collectively, these studies include acute, subchronic
, and chronic toxicity, including a ssessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring

. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive ef fects in different taxonomic groups

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

. How ever, as required by FFDCA section 408(p ), thifensulfuron methyl is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide activ e and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the s tatutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems

. chemicals that go through Tier 1 sc reening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is des igned to identify any adverse endocrine

- related effects caused by the substance, and establish a dose

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

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

. Between Oc tober 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients

. A second list of che micals identified for EDSP screening was published on June 1 4, 2013 2 

### and includes some pesticides

s che duled for Registration Review and che micals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors

.
For further information on the status of the EDSP, the policies and procedures, the list s of che micals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 3

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of chemicals.
3 http://www.epa.gov/endo/

### Page 13 of 37

5.0 Dietary Exposure and Risk Assessment

5.1 Water Residue Profile

Screening groundwater

- sourced drinking water exposure estimates were generated with the Pesticide Root Zone Model for GroundWater ( PRZM

- GW; v.1.07) for use in the sulfonylurea (SU) dietary risk assessments

. Rather than produce chemical

- specific estimated d rinking water concentrations (EDWCs) following the usual assessment procedures, EFED provided coarse

screen estimates that should exceed upper

- bound, chemical

- specific EDWCs for any SU

. This was achieved by using model inputs that represent the use pattern of highest exposure from any SU, the highest soil mobility of any SU residue of concern, and the highest persistence to any route of degradation over time

. The resulting coarse

- screen EDWCs from PRZM

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

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

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

- breakthrough mean value of 492 μg/L (0.492 ppm), respectively

.

Table 5.1

. PRZM

- GW Coarse

- Screen EDWCs for Sulfonylureas 1

.

Modeled Scenario K d or K OC Initial Application Dates (days post

emergence) Max. Daily Conc.

(μg/L) Mean

Breakthrough Time (yrs) Post

breakthrough Mean (μg/L)
WI corn K d 7 449 11.5 415

K OC 7 504 6.9 425
DMV corn K d 7 489 5.3 369

K OC 7 560 3.3 378
FL citrus K d 7 429 3.2 351

K OC 7 467 2.3 349 FL potato K d 7 375 2.6 272

K OC 7 407 2.2 275 GA peanut K d 7 197 5.2 156

K OC 7 206 3.9 158
NC cotton K d 7 640 8.7 492

K d 37 641 8.7 491
K d 67 637 8.7 490
K OC 7 742 5.7 484
K OC 37 751 5.7 483
K OC 67 744 5.7 482

1 Maximum values are bold ed.



### 5.2 Food Residue Profile

The residue chemistry database for thifensulfuron methyl is considered to be complete and no additional data are required at this time. The residue of concern for dietary risk assessment of
t hifensulfuron methyl is the parent compound itself

. In conducting this assessment, HED has

### Page 14 of 37

assumed tolerance

- level residues in the raw agricultural commodities and processed products of registered crops
, and that 100 percent of those crops are treated with thifensulfuron methyl

.

5.3 Dietary Exposure and Risk Estimates

New dietary exposure and risk estimates were obtained for this assessm ent in order to incorporate the new EDWCs (see Section 5.1). The e xposure and risk estimates were made using 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 exceed 100% o f the population adjusted dose (PAD)

. In the case of thifensulfuron methyl , the dietary risk estimates (Table 5.3) are not of concern. The acute estimate is 2.6% of the a PAD for women of child

- bearing age at the 95 th 

### percentile
, and the chronic estimates r ange from 18 to 63 % of the cPAD across all representative population groups

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

- level residues, 100 % crop treated, upper

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

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

.

Table 5 .3

. Summary of dietary exposure and risk estimates for thifensulfuron methyl

. Acute Estimates (95 th Percentile) Chronic Estimates

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

Not Applicable Not Applicable 0.0105 24 All Infants (< 1 year old) 0.0270 63 Children 1

- 2 years old 0.0154 36 Children 3

- 5 years old 0.0131 30 Children 6

- 1 2 years old 0.0094 22 Youth 13

- 19 years old 0.0077 18 Adults 20

- 49 years old 0.0105 24 Adults 50

- 99 years old 0.0103 24 Female 13

- 49 years old 0.0412 2.6 0.0104 24



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

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

. Therefo re, a quantitative residential exposure assessment was not performed.

6.1 Spray Drift

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

### Page 15 of 37

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

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

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

.

Thifensulfuron methyl is registered for use on cereal grains (barley, field corn, oats, rice, sorghum, wheat, and triticale), oilseed crops (canola, rape, and flax), soybeans, s ugar beets,
cotton , and chicory

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

. Corn, wheat, sorghum
, and cotton are the predominant registered agricultural usage crops ; therefore, they are considered representative of the registered uses

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

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

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

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

The spray drift asse ssment is based on dermal and incidental oral exposures

. The highest exposure resulted from drift following thifensulfuron methyl applications using aerial equipment for children 1 to <2 years old ( combined dermal + incidental oral MOEs ≥ 1,300, with a LOC =100)

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

. See Tables 6.1.1 and 6.1.2 for detai led results.

1 HED’s default assumption that 10% of the application is available for transfer on day 0 following the application and the residues dissipate at a rate of 10% each following day. Table 6.1.1

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

. Crop/Rate Group Spray Type/ Nozzle Configuration Appl

. Rate (lb ai/A) TTR 1 (ug/cm 2 ) At Edge of the Field

Dermal Aerial Fine to Medium 0.028 0.0031 2,600 Groundboom High Boom Very fine to Fine 3,600 Airblast Sparse 4,600

Table 6.1.2

. Children (1<2 years old) Risk Estimates (MOEs) Related to Derma l and Indirect Exposure to Spray Drift from Thifensulfuron 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 0.028 0.0031 1,300 Groundboom High Boom Very fine to Fine 1,800 Airblast Sparse 2,300

### Page 16 of 37 1 HED’s default assumption that 10% of the application is available for transfer on day 0 following the application and the residues dissipate at a rate of 10% each following day.



### 6.2 Residential Bystander Post

- Application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications

. The A gency sought expert advice and input on issues related t o volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109m eeting.html)

. The A gency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis

. 4 

### During Registration Review, the A gency will

use this analysis to determine if data (i.e., flux stu dies, route

- specific inhalation toxicological studies) or further analys e s are required for thifensulfuron methyl

.

7.0 Aggregate Exposure/Risk Characterization

The Food Quality Protection Act of 1996 directs EPA to assess aggregate exposure to pesticide chemical residues, including all anticipated dietary exposures and all other exposures for which there is reliable information

. In the case of thifensulfuron methyl , aggregate exposure and risk estimates are equivalent to the dietary exposure and risk esti mates in Section 5 .3 , above, and are not of concern

.

8.0 Cumulative Exposure/Risk Characterization

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

- for

- screening

analysis.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 availa ble 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) 5 

### and conducting cumulative risk assessments (CRA) 6



### . The Agency has utilized this framework to evaluate the SUs of which orthosulfamuron is a member (J. D’Agostino; D428798; 9/9/15). Although the SUs share some chemical and toxicological characteristics, the toxicological database does not support a testable h ypothesis for a common mechanism of action. No further mechanistic data are required and no further cumulative evaluation is necessary.

4 Available at: ht tp://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219

. 5 Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common Mechanism of Toxicity (USEPA, 1999)
6 Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity (USEPA, 2002)

### Page 17 of 37

9.0 Occupational Exposure/Risk Characterization

9.1 Occupational Handler Exposure/Risk Estimates

Based on current labeling, types of equipment
, and techniques that can potentially be used, occupational handler exposure is expected from the registered uses

. Therefore, as part of this assessment, HED re

- evaluated occupational exposures in order to ensure that the estim ates reflect the most recent policies and procedures. The quantitative exposure /risk assessment developed for occupational handlers is based on the scenarios listed in Table 9.1

. Based on the use pattern and agricultural practices, occupational exposure s f rom the registered food uses are expected to be short

- term (1

- 30 days) and intermediate

- term (i.e., 1

- 6 months) in duration

. Since the same endpoint and point of departure were selected for short

- and intermediate

- term durations, short

- term exposure and ri sk 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 Handler Exposure Data and Assumptions

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

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

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

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

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

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

. A dermal absorption factor of 100 % was u sed for the exposure assessment since dermal absorption data are not available for thifensulfuron methyl

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

. Sources of generic handler data, used as surroga te data in the absence of chemical

- specific data, include Pesticide Handler's Exposure Database ( PHED ) 1.1, and the Agricultural Handler Exposure Task Force ( AHETF ) database

. Some of these data are proprietary (e.g., AHETF data), and subject to the data pr otection 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 7



### . ” HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 8



### .

Area Treated or Amount Handled: The inputs for area treated or amount handled were based on the Science Advisory Council for Expo sure Policy 9.1: Standard Values for Daily Acres Treated

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

- exposure

- table.pdf
8 Available: http://www.epa.gov/pesticides/science/handler

- exposure

- data.html

### Page 18 of 37

in Agriculture (values are listed in Table 9.1)

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

Risk Estimate Equations : The algorithms used to estimate non

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

Combining Exposures/Risk Estimates: Dermal and inhalation risk estimates wer e combined in this assessment since the toxicological effects for these exposure routes were similar and based on the same POD and study

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

Total MOE = Point of Departure (mg/k g/day) ÷ Combined Dermal + Inhalation 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 greater than 100 at baseline level of risk mitigation (i.e., baseline attire with no gloves or respirator), baseline attire with chemical

- resistant gloves or engineering control s (i.e., enclosed systems or enc losed cockpits for aerial applications ) and, therefore, are not of concern

. The lowest MOE ( 2 40 ) is associated with total exposure during mixing/loading activities for a dispersible granule formulation being applied to 350 acres using chemigation equipment

. All other MOEs were higher, ranging from 2 7 0 to 8,000

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

. While HED presents quantitative risk estimates for human flaggers where app ropriate, 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 steadi ly from the mid 1990’s

. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent (2012) NAAA survey

. The Agency will continue to monitor all ava ilable 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 socks); per the Agency’s Worker Protection Standa rd stipulations for engineering controls, pilots are not required to wear protective gloves for the duration of the application

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

### Page 19 of 37

Table 9.1

. Short

- term Handler Exposure and Risk Estimates for Thifensulfuron methyl

. Exposure Scenario Unit Exposure (ug/lb ai) [Mitigation Level] ab Application Rate (lb ai/A) c Area

Treated (Acres) d Dermal Inhalation Total MOE i

Dermal Inhalation Dose , mg/kg/day e MOE f Dose ,

mg/kg/day g MOE h

Mixer/Loader Dry Flowable ( D ispersible Granule) for Aerial Application 51.6 (Baseline, Gloves) 8.96

(No respirator) 0.028 1,200 0.0218 320 0.00378 1,900 270

Dry Flowable ( D ispersible Granule) for Groundboom Application 227 (Baseline) 8.96

(No respirator) 0.028 200 0.0160 440 0.00063 11,000 420

Dry Flowable ( D ispersible Granule) for Airblast Application 227 (Baseline) 8.96

(No respirator) 0.028 40 0.00319 2,200 0.000126 56,000 2,100

Dry Flowable ( D ispersible Granule) for Chemigation Application 227 (Baseline) 8.96

(No respirator) 0.028 350 0.0279 250 0.0011 6,400 240

Applicator Sprays for Aerial Application 2.08 (Engineering Controls

– Enclosed Cockpit) 0.0049

(Engineering Controls

– Enclosed Cockpit) 0.028 1,200 0.00088 8,000 0.0000021 3,400,000 8,000

Sprays for Groundboom Application 78.6 (Baseline) 0.34

(Baseline) 0.028 200 0.00553 1,300 0.0000239 290,000 1,300

Sprays for Airblast Application 1,770 (Baseline) 4.71

(Baseline) 0.028 40 0.02490 280 0.0000661 110,000 280

Flagger Sprays for Aerial Application 11 (Baseline) 0.35

(Baseline) 0.028 350 0.00135 5,200 0.000043 160,000 5,000

a. Mitigation Level: “ baseline ” (i.e., single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no gloves, and no respirator ); “ engineering controls for aerial applications ” (i.e., enclosed cockpit). b. Based on the “ Occupational Pesticide Handler Unit Exposur e Surrogate Reference Table ” (February, 2015).

c. Based on the maximum single application rates listed on registered labels (Table 3.2). d. Based on the Science Advisory Council for Exposure Policy 9.1: Standard Values for Daily Acres Treated in Agriculture

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

. f. Dermal MOE = Dermal NOAEL (mg/kg/day)/ Dermal Dose (mg/kg/day). LOC=100.
g. Inhalation Dose (mg/kg/day) = [Rate x UE x 0.001 x Acres Treated or Amount Handled ]/BW (80 kg). h. Inhalation MOE = Inhalation NOAEL (mg/kg/day)/ Inhalation Dose (mg/kg/day). LOC=100. i. Total MOE = NOAEL (mg/kg/day)/ [Dermal Dose + Inhalation Dose (mg/kg/day)]. LOC=100. j. At baseline PPE, the dermal MOE is 51 and is of concern

.

### Page 20 of 37

9.2 Occupational Post

- application Exposure/Risk Estimates

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesti cide (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 applicat ions, relative to harvest activities, can greatly reduce the potential for post

- application exposure. Since the same endpoint and point of departure were selected for short

- and intermediate

- term durations, short

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

term exposure and risk

. 9.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application a ctivities in previously treated fields

. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides

. The A gency sought expert advice and input on issues related to volatilization of pes ticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html)

. The A gency has

ev aluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

OPP

- 2014

- 0219)

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

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

. In addition, the Agency is continuing to evaluate the available post

- application inhalation exposure data g enerated by the Agricultural Reentry Task Force

. Given these two efforts, the Agency will continue to identify the need for and, subsequently, the way to incorporate occupational post

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

Alt hough a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational handlers

. Handler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than post

- application exposure

. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

9.2.2 Occupational Post

- applicati on Dermal Exposure/Risk Estimates

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

- application dermal risk assessment, including the following:

### Page 21 of 37

Exposure Duration: Based on the use pattern and agricultural practices, occupational post

application exposure from the registered food uses is expected to be short

- term (1

- 30 days) and intermediate

- term (i.e., 1

- 6 months) in duration

. Since the same endpoint and point of d eparture 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 surrogate data in the absence of chemical

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

. The standard values recommended for use in predicting post

- application exposure that are used in this assessment, known as “tra nsfer coefficients”, are presented in the ExpoSAC Policy 3 9 

### ” which, along with additional information about the ARTF data, can be found at the Agency website 10



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

application activities and associated transfer coefficients for the proposed crops/use sites.

Table 9.2.2

. 1

. Anticipated High

- contact Post

- Application Activities and Dermal Transfer Coefficients.

Proposed Crops Policy Crop

Group Category Crop

Height Foliage

Density Transfer

Coefficients (cm 2 /hr ) Activities

Corn Field, row,

tall High Full 1,900 Irrigation (Hand set)

Barley, Wheat Field, row,

medium Low Full 1,100 Scouting

Safflower Field, row,

medium Low Full 1,900 Irrigation (Hand set)

Beets, Sugar Field, row,

medium Low Full 1,100 Hand, Harvesting

Soybean Field, row,

medium Low Full 1,100 Scouting

Sorghum Field, row,

tall High Full 210 Scouting



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

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

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

Dislodgeable Foliar Residues: Chemical

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

. 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.

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

- app

- exposure

- data.html

### Page 22 of 37

Risk Estimate Equations : The algorithms used to estimate non

- cancer exposure and dose for occupational post

- application workers can be found in Appendix C.

Occupational Post

- application Non

- Cancer Dermal Risk Estimates

A summary of the post

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

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

. This dermal post

- application assessment is considered conservative because thifensulfuron m ethyl is mainly applied d uring pre

- pant or at planting. Post

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

. All other scenarios involving lower c ontact activities and lower f oliage / crop height would have higher MOEs and are also not of concern.

A summary of the post

- application dermal exposure and risk estimates from use of thifensulfuron m ethyl on cotton during harvesting activities is provided i n Table 9.2.2.3

. T hifensulfuron m ethyl is applied on cotton either 13

- 22 days prior to planting or at planting, leaving a 5

- month period between application and harvest. Dislodgeable residue data for cotton bolls were not available for thifensulfuron m ethyl ; therefore, the dislodgeable residue value for cotton bolls was estimated from the field trial residues in/on cotton gin byproducts. The field trial residue is an upper

- bound residue value collected at the pre

- harvest interval which represents the

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

. It is considered appropriate as an estimate of dislodgeable boll residue, and is used as a screening level approach to estimating exposure

. Furthermore, in t he case of thifensulfuron

m ethyl, residues in cotton gin byproducts were below the analytical method limits of quantification (LOQ ; 0.02 mg ai /kg ) and detection (LOD ; 0.006 mg ai /kg ) in all samples. Therefore, the 0.02

- mg/kg residue estimate used in the po st

- application dermal risk assessment for use on cotton is very conservative and results in exposure estimates that are likely to significantly overestimate actual exposures for that scenario. Post

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

.

Table 9.2 .2.2

. Occupational Post

- application Non

- Cancer Exposure and Risk Estimates for Thifensulfuron Methyl

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

Short

- and Intermediate

- term

Corn Irrigation (Hand set) 1,900 0.08 0.015 470
Barley, Wheat Scouting 1,100 0.08 0.009 810

Safflower Irrigation (Hand set) 1,900 0.08 0.015 470
Beets, Sugar Hand, Harvesting 1,100 0.08 0.009 810 Soybean Scouting 1,100 0.08 0.009 810 Sorghum Scouting 210 0.08 0.002 4,200

1. DFR = Application Rate × F × (1

- D) t × 4.54E8 μg/lb × 2.47E

- 8 acre/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 (100%)] 

###  BW (kg).

### Page 23 of 37

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

Table 9.2.2.3

. Post

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

Crop Maximum

Seasonal Application Rate (lb ai/A) Activity TC 1 (g cotton/hr) Days After

Treatment Residue from

Cotton Field Trial 2 (mg ai/g cotton) Daily Dose

(mg/kg/d) 3 MOE 4

Short

- and Intermediate

- term

Cotton 0.025 Harvesting Mechanical (Module Builder) 900

123 0.00002 0.00 18 3, 9 00

Harvesting Mechanical (Picker Operator; Raker) 2400 0.00 48 1, 4 00

Harvesting Mechanical (Tramper) 5050 0.01 01 69 0

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

- Foliar Transfer Coefficient Table, March 2012 (p 122). 2. Residue Value from Cotton Field Trial (mg ai/g cotton) = (0. 0 2 mg ai/kg cotton) (0.001 k g/g) = 0.000 02 mg ai/g cotton. 3. Dermal Dose (mg/kg/day) = [Cotton Field Trial Residue Value adjusted (mg ai/g cotton) x TC (g cotton/hr) x hr/day (8 hrs/day) x DAF (100%)]/ BW (80 kg). 4. Dermal MOE = NOAEL ( 7 mg/kg/day)/Dermal Dose (mg/kg/day); LOC = 100.


### Restricted Entry Interval

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

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

. It is not a skin sens itizer

. Short

- and intermediate

- term post

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

- application activities

. Under 40 CFR 156.208 (c) (2) (iii), ai’s classified as Acute Toxicity Category III or IV for acute dermal, eye irritation
, and primary skin irritation are assigned a 12

- hour REI

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

- application exposures t o thifensulfuron

.

10.0 Public Health and Pesticide Epidemiology Data D42 5818 , S. Recore, 24 March 2015

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

. At the tim e, there were no thifensulfuron methyl incidents found in the Main Incident Data System ( IDS ) and 12 incidents reported to Aggregate IDS

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

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

re ported involving thifensulfuron methyl in Main IDS involving multiple chemicals and five incidents reporte d to Aggregate IDS

. Further, a query of SENSOR

- Pesticides 1998

- 2011 identifies nine cases involving multiple active ingredients. These incidents were classified as low severity.

### Page 24 of 37

Based on the low frequency and mostly low severity of incident ca ses reported for thifensulfuron methyl in both IDS and NIOSH SENSOR

- Pesticides, there does not appear to be a concern at this time that would warrant further investigation

. The Agency will continue to monitor the incident information and if a concern is triggered, add itional analysis will be conducted.

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

. Thifensulfuron methyl is not included in the AHS ; therefore, the AHS d oes not provide information relevant to this assessment

.

11.0 Literature References

A literature search was performed for thifensulfuron m ethyl

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

.

1 2 .0 References

Author Barcode Date Title Drew, W

. D 361902 29 Jan 2010 Thifensulfuron Methyl. Human Health Risk Assessment for the Proposed Food/Feed Use of the Herbicide (Associated with Regional Section 3 Registration) on Safflower. Dotson, D

. D383624 15 Mar 2011 Thifensulfuron Methyl. Hu man Health Assessment Scoping D o c ument in Support of Registration Review. Recore, S

. D383694 30 Nov 2010 Thifensulfuron M ethyl: Review of Human Incidents Drew, W

. D391088 1 Jun 2012 Thifensulfuron Methyl. Human Health Risk Assessment for the Proposed Use of the Herbicide on Chicory. Recore, S

. D425818 24 Mar 2015 Thifensulfuron M ethyl: Tier 1 Update Review of Human Incidents/Epidemiology for Draft Risk Assessment Smegal, D. TXR# 0054114 7 Mar 2012 Thifensulfuron Methyl: Summary of Hazard and Science Policy Council (HASPOC) Meeting of February 23, 2012: Recommendations on the need for 28

- day inhalation and 28

- day dermal toxicity studies. Orrick, G. D427429 12 Dec 2015 Drinking Water Exposure assessment for the Registratio n Review of 22 Sulfonylurea Herbicides

### Page 25 of 37

Appendix A. Toxicology Data Requirements and Toxicology Profile

A.1 . Toxicity Requirements

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

TABLE A.1 Toxicology Data Requirements for Thifensulfuron Methyl

. Test Required Satisfied
870.1100 Acute Oral Toxicity

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

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

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

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

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

................................ ................................ .... yes yes yes yes yes yes yes

yes yes yes yes yes 870.3100 Oral Subchronic (Rodent)

................................ ............................ 870.3150 Oral Subchronic (Non

- Rodent)

................................ .................... 870.3200 21/28

- Day Dermal

................................ ................................ ....... 870.3250 90

- Day Dermal

................................ ................................ ............ 870.3465 21/ 90

- Day Inhalation

................................ ................................ .. yes yes yes

no

no yes

yes no*

no no* 870.3700a Developmental Toxicity (Rodent)

................................ ............... 870.3700b Developmental Toxicity (Non

- Rodent)

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

................................ ................................ ............... yes yes yes yes

yes yes 870.4100a Chronic Toxicity (Rodent)

................................ ........................... 870.4100b Chronic Toxicity (Non

- Rodent)

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

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

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

................................ ................................ .. yes yes yes yes yes yes

yes yes yes yes 870.5100 Mutagenicity

– Gene Mutation (Bacterial)

................................ .. 870.5300 Mutagenicity

– Gene Mutation (Mammalian)

............................. 870.5375 Mutagenicity

– Structural Chromosomal Aberrations

................. 870.5395 Mutagenicity

– Mammaliam Erythrocyte Micronucleus

............. 870.5550 Mutagenicity

– Unscheduled DNA Synthesis

............................. 870.5915 Mutagenicity

– In Vivo Sister Chromatid Exchange

.................... yes yes yes

no

no

no yes

yes yes yes yes

no 870.6100a Acute Delayed Neurotoxicity (Hen)

................................ ............ 870.6100b 90

- Day Neurotoxicity (Hen)

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

.............................. 870.6200b 90

- Day Neurotoxicity Screening Battery (Rat)

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

................................ ...................... no

no yes yes

no no

no yes yes

no
870.7485 General Metabolism

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

................................ ................................ ...... yes

no yes

no 870.7800 Immunotoxicity Y es yes

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

.

### Page 26 of 37

A.2. Toxicity Profiles

TABLE A.2.1 Acute Toxicity Profile for Technical Thifensulfuron Methyl

. Guideline Number Study Type MRID Number Results Tox Category 870.1100 Acute Oral

- Rat 00146033 LD 50 >5000 mg/kg (M+F) IV 870.1100 Acute Oral

- Rat 00146034 LD 50 >5000 mg/kg (M+F) IV 870.1200 Acute Dermal 00146035 LD 50 >2000 mg/kg (M+F) III 870.1200 Acute Dermal 40467606 LD 50 >2000 mg/kg (M+F) III 870.1300 Acute Inhalation 00143657 LC 50 >7.9 mg/L/4 hours I V 870.2400 Primary Eye Irritation 00143658 Moderate irritation. III 870.2500 Primary Skin Irritation 40921502 Slight irritation. IV 870.2600 Dermal Sensitization 00146037 Not a sensitizer. NA* * NA = Not Applicable

.

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

. Guideline Number Study Title MRID Number Results

870.3100 90

- Day Oral

Toxicity

- Rat (diet) 00143660 (1984)

Acceptable/guideline ppm = 0, 100, 2500, & 7500 mg/kg/day (M/F) = 0/0, 7/9, 177/216, 559/697 NOAEL = 7 (males), 9 (females) mg/kg/day. LOAEL = 177 (males), 216 (females) mg/kg/day, based on decreased body weight, body weight gain, and spleen weight in males only (13%).

870.3100 90

- Day Oral

Toxicity

- Mouse (diet) 00161276 (1984)

Acceptable/guideline ppm=0, 500, 2500 & 7500 mg/kg/day (M/F) = 0/0, 97/123, 523/690 & 1427/2287 NOAEL = 1427 (males), 2287 (females) mg/kg/day. LOAEL = could not be determined.

870.3150 13

- Week Oral

Toxicity

- Dog (diet) 00145160 (1984)

Acceptable/guideline ppm = 0, 75, 1500 & 7500 mg/kg/day (M&F) = 0, 1.88, 37.5 & 187.5 NOAEL = 37.5 males & females mg/kg/day. LOAEL = 187.5 males & females mg/kg/day, based on decreased body weight and adrenal weight in high

- dose males.

870.3200 21/28

- Day

Dermal Toxicity

– Rat Waived by HASPOC ( TXR# 0054114)

870.3465 21/ 90

- Day

Inhalation Waived by HASPOC ( TXR# 0054114)

870.3700a Developmental

Toxicity

- Rat (gavage) 00143661 (1984)

Acceptable/guideline mg/kg/day = 0, 26, 159, & 725 (analytically determined doses) Maternal NOAEL = 725 mg/kg/day. LOAEL = could not be determined. Developmental NOAEL = 159 mg/kg/day. LOAEL = 725 mg/kg/day, based on decreased mean fetal body weights, and increased incidence of small renal papillae. 870.3700b Developmental

Toxicity

- Rabbit (gavage) 00161277 (1984)

Acceptable/guideline mg/kg/day = 0, 22, 158 & 511 (analytically determined doses) Maternal NOAEL = 158 mg/kg/day. LOAEL = 511 mg/kg/day, based on decreased mean body weights. Developmental NOAEL = 511 mg/kg/day. LOAEL = could not be determined. 870.3800 Reproduction (2

- 00161278 (1985) Parental/Systemic NOAEL = 175 (males), 244

### Page 27 of 37

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

. Guideline Number Study Title MRID Number Results

Generation)

– Rat (diet) Acceptable/guideline

ppm = 0, 25, 500 & 2500 mg/kg/day F 0 M/F = 0/0, 1.8/2.4, 34/48 & 175/244 mg/kg/day F 1b M/F = 0/0, 1.7/2.1, 36/43 & 180/212 (females) mg/kg/day. LOAEL = could not be determined. Reproductive NOAEL = 180 (males), 212 (females) mg/kg/day. LOAEL = could not be determined. Offspring NOAEL = 180 (males), 212 (females) mg/kg/day. LO AEL = could not be determined.

870.4100 Chronic (1 year)

–

Dog (diet) 00161273 (1986)

Acceptable/guideline ppm = 0, 50, 750 & 7500 mg/kg/day (M&F) = 0, 1.25, 18.75 & 187.5 NOAEL = 18.75 (males & females) mg/kg/day. LOAEL = 187.5 (males & females) mg/kg/day
, based on increased liver weights in males, and increased relative thyroid/parathyroid weights in females, with decreased body weight and body weight gain in females after week 22.

870.4200 Carcinogenicity

(18

- Month)

– Mouse (diet) 00161275 (1985)

40340321 (1987) (individual pathology sheets) Acceptable/guideline ppm = 0, 25, 750 & 7500 mg/kg/day (M/F) = 0/0, 3.2/4.3, 97/128 & 979/1312 NOAEL = 979 (males), 4.3 (females) mg/kg/day. LOAEL = could not be determined (males), 128 (females) mg/kg/day, bas ed on a decrease in terminal body weights in the mid and high doses.

No evidence of carcinogenicity.

870.4300 Chronic/

Carcinogenicity (2

- Year)

– Rat (diet) 00161274 (1986)

Acceptable/guideline 40340324 (1987) Supplement 40340323 (1987) Supplement ppm = 0, 25, 500 & 2500 mg/kg/day (M/F) = 0/0, 0.96/1.3, 20/26 & 120/133 NOAEL = 20 (males), 26 (females) mg/kg/day. LOAEL = 120 (males), 133 (females) mg/kg/day, based on decreased body weight and body weight gain.

No evidence of carcinogenicity.

870.5100 870.5265 Gene Mutation in

S. typhimurium and E. coli 00143662 (1984)

Acceptable/guideline No mutagenic response ± S9 activation in TA 1535, 97, 98 & 100

. Cytotoxicity seen at HDT.

870.5300 Gene Mutation in

CHO Mammalian Cells at HGPRT Locus 00145161 (1987 )

40340325 (1987) Acceptable/guideline No mutations at HDT (7mM), which was above limit of solubility.

870.5375 CHO Cell

Cytogenetics 44710403 (1996)

Acceptable/guideline No evidence of chromosomal aberrations when tested up to cytotoxic or solubility limit concentrations. 870.5395 In vivo Rat Bone

Marrow Micronucleus 00145560 (1984)

Acceptable/guideline Negative for clastogenic response at 5000 mg/kg.

### Page 28 of 37

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

. Guideline Number Study Title MRID Number Results

870.5550 Unscheduled

DNA Synthesis in Primary Mammalian Cells 00143663 (1985)

Acceptable/guideline N o significant increase in UDS.

870.6200a Acute

Neurotoxicity Screening Battery

– Rat (gavage) 48817901 (2012)

0, 200, 700, or 2000 mg/kg/day NOAEL = 2000 mg/kg/day (limit dose). LOAEL not determined

.

870.6200b Subchronic

Neurotoxicity Study

– Rat (diet) 48817902 (2012)

ppm = 0, 750, 2 500, & 7500 mg/kg/day (M/F) = 0/0, 42/46, 136/158, or 421/489 NOAEL = 421 mg/kg/day (the HDT)

. LOAEL not determined.

870.7485 Metabolism Study

– Rat (gavage) 00161281 (1986)

Acceptable/guideline low dose = 20 mg/kg high dose = 2000 mg/kg Most of the radioactivity was recovered in the urine and feces (parent with 5 metabolites) with parent accounting for 55 and 72% for males and females, respectively

. Minor metabolites included DPX

M6316 acid (2.3

- 2.4%), O

- demethyl DP X

- M6316 (0.4

- 0.5%), triazine amine (0.5%) and lesser amounts of 2

- ester

- e

- sulfonamide and thiophene sulfonamide

. Fecal metabolite profile was similar to that in urine

. Unchanged DPX

- M6316 acid is the primary excretory product (18 or 12% in males and female s, respectively)

. Three metabolites remained unidentified.

870.7600 Dermal

Absorption

– Rats No study has been submitted.

870.7800 Immunotoxicity

Study

– Rat (diet) 48686101 (2011)

Acceptable/guideline Females only ppm = 0, 250, 750, 2500, 7000 mg/kg/day = 0, 19, 55, 192, 529 Systemic Effects NOAEL = 529 mg/kg/day LOAEL = not attained (no clinical signs of toxicity) Immunotoxicity Effects NOAEL = 529 mg/kg/day LOAEL = not attained (no immunotoxic effects)

### Page 29 of 37

Appendix B

. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical

. These data are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements

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

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

- exposure

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

- app

- exposure

- data.html

.

### Page 30 of 37

Append ix 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/lb ai), AR = m aximum application rate according to registered label s (lb ai / A), and A = a rea treated or amount handled (e.g., A/day 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 calculat ed 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 ris k 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).

### Page 31 of 37

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 

### )

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% (unitless), 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

- applic ation 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

### Page 32 of 37

where:

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

### Page 33 of 37

Appendix D

. Dietary Exposure/Risk Modeling Input and Output

US EPA Ver. 3.18, 03

- 08

- d
DEEM

- FCID Acute analysis for THIFENSULFURON METHYL Residue file name: Thifensulfuron methyl.R08 Analysis Date 07

- 29

- 2015 Residue file dated: 07

- 29

- 2015/08:18:22 Reference dose (aRfD) = 1.59 mg/kg bw/day Comment: Ac ute for females 13

- 49 only

---------------------------------------------------------------------------------- EPA Crop Def Res Adj.Factors Comment Code Grp Food Name (ppm) #1 #2

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

- babyfood 0.050000 1.000 1.000 150002600 0 15 Barley, flour 0.050000 1.000 1.000 1500026001 15 Barley, flour

- babyfood 0.050000 1.000 1.000 1500027000 15 Barley, bran 0.050000 1.000 1.000 0101100000 1AB Chicory, roots 0.010000 1.000 1.000 0200101000 2 Chicory, tops 0.010000 1.000 1.000 1500120000 15 Corn, field, flour 0.050000 1.000 1.000 1500120001 15 Corn, field, flour

- babyfood 0.050000 1.000 1. 000 1500121000 15 Corn, field, meal 0.050000 1.000 1.000 1500121001 15 Corn, field, meal

- babyfood 0.050000 1.000 1.000 1500122000 15 Corn, field, bran 0.050000 1.000 1.000 1500123000 15 Corn, field , starch 0.050000 1.000 1.000 1500123001 15 Corn, field, starch

- babyfood 0.050000 1.000 1.000 1500124000 15 Corn, field, syrup 0.050000 1.000 1.000 1500124001 15 Corn, field, syrup

- babyfood 0.05000 0 1.000 1.000 1500125000 15 Corn, field, oil 0.050000 1.000 1.000 1500125001 15 Corn, field, oil

- babyfood 0.050000 1.000 1.000 2003128000 20C Cottonseed, oil 0.020000 1.000 1.000 2003128001 20C Cottonseed, oil

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

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

- babyfood 0.050000 1.000 1.000 2 001319000 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

- baby food 0.050000 1.000 1.000 1500324000 15 Rice, brown 0.050000 1.000 1.000 1500324001 15 Rice, brown

- babyfood 0.050000 1.000 1.000 1500325000 15 Rice, flour 0.050000 1 .000 1.000 1500325001 15 Rice, flour

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

- babyfood 0.050000 1.000 1.000 2002330000 20B Saf flower, oil 0.050000 1.000 1.000 2002330001 20B Safflower, oil

- babyfood 0.050000 1.000 1.000 1500344000 15 Sorghum, grain 0.050000 1.000 1.000 1500345000 15 Sorghum, syrup 0.050000 1.000 1.000 0600347000 6 Soybean, seed 0.100000 1.000 1.000 0603348000 6C Soybean, flour 0.100000 1.000 1.000 0603348001 6C Soybean, flour

- babyfood 0.100000 1.000 1.000 060034 9000 6 Soybean, soy milk 0.100000 1.000 1.000 0600349001 6 Soybean, soy milk

- babyfood or in 0.100000 1.000 1.000 0600350000 6 Soybean, oil 0.100000 1.000 1.000 0600350001 6 Soybean, oil

- babyfood 0.100000 1.000 1.000 1500381000 15 Triticale, flour 0.050000 1.000 1.000 1500381001 15 Triticale, flour

- babyfood 0.050000 1.000 1.000 8601000000 86A Water , direct, all sources 0.751000 1.000 0.655 Fact. 2=492/751 (chronic/acute) 8602000000 86B Water, indirect, all sources 0.751000 1.000 0.655 F act. 2=492/751 (chronic/acute) 1500401000 15 Wheat, grain 0.050000 1 .000 1.000 1500401001 15 Wheat, grain

- babyfood 0.050000 1.000 1.000 1500402000 15 Wheat, flour 0.050000 1.000 1.000 1500402001 15 Wheat, flour

- babyfood 0.050000 1.000 1.000 1500403000 15 Whe at, germ 0.050000 1.000 1.000

### Page 34 of 37

1500404000 15 Wheat, bran 0.050000 1.000 1.000

US EPA Ver. 3.18, 03

- 08

- d DEEM

- FCID ACUTE Analysis for THIFENSULFURON METHYL NHANES 2003

- 2008 2

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

- 29

- 2015/08:19:38 Residue file dated: 07

- 29

- 2015/08:18:22 RAC/FF intake summed over 24 hours Run Comment: "Acute for fe males 13

- 49 only"

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

Summary calculations

-- per capita:

95th Percentile 99th Percentile 99.9th Percentile Exposure % aRfD Expo sure % aRfD Exposure % aRfD

---------- -------- ---------- -------- ---------- -------- Female 13

- 49: 0.041152 2.59 0.060229 3.79 0.085186 5.36

US EPA Ver. 3.16, 03

- 08

- d DEEM

- FCID Chronic analysis for THIFENSULFURON METHYL NHANES 2003

- 2008 2

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

- 29

- 2015/08:21:58 Residue file dated: 07

- 29

- 2015/08:18:22 Reference dose (RfD, Chronic) = .043 mg/kg bw/day COMMENT 1: Acute for females 13

- 49 only

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

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

Total Exposure

-------------------------- --------- Population mg/kg Percent of Subgroup body wt/day Rfd

-------------------------------------- ------------- ---------------- Total US Popul ation 0.010530 24.5% Hispanic 0.010092 23.5% Non

- Hisp

- White 0.010816 25.2% Non

- Hisp

- Black 0.00 8725 20.3% Non

- Hisp

- Other 0.012139 28.2% Nursing Infants 0.009502 22.1% Non

- Nursing Infants 0.034765 80.8% Female 1 3+ PREG 0. 009896 23.0% Children 1

- 6 0.013737 31.9% Children 7

- 12 0.008938 20.8% Male 13

- 19 0.007336 17.1% Female 13

- 19/NP 0.008148 18.9% Male 20+ 0.009791 22.8% Female 20+/NP 0.010976 25.5% Se niors 55+ 0.010099 23.5% All Infants 0.026965 62.7% Female 13

- 50 0.010430 24.3% Children 1

- 2 0.015430 35.9% Children 3

- 5 0.013053 30.4% Children 6

- 12 0.009403 21.9% Youth 13

- 19 0.007745 18 .0% Adults 20

- 49 0. 010473 24.4% Adults 50

- 99 0.010305 24.0% Female 13

- 49 0.010420 24.2%

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

### Page 35 of 37

Appendix E. Nomenclature and Physical/Chemical Properties

TABLE E.1 Thifensulfuron M ethyl Nomenclature
Chemical structure

Common name Thifensulfuron methyl Molecular formula C 12 H 13 N 5 O 6 S 2 Molecular weight 387.38 Company experimental name DPX

- M6316 IUPAC name Methyl 3

- (4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- ylcarbamoylsulfamoyl) thiophene

2

- carboxylate CAS name Methyl 3

- [[[[(4

- methoxy

- 6

- methyl

- 1,3,5

- triazin

- 2

- yl)amino]carbonyl]amino] sulfony l]

- 2

- thiophenecarboxylate CAS registry number 79277

- 27

- 3

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

Parameter Value Reference Melting point/range (oC) 171.1 ± 1.2 MRID #47138301 (D342084; D. Dotson; 17 April 2008) pH 4.0 Density (g/cm 3 ) 1.58 ± 0.004 Water solubility (g/L at 25oC) pH 5 0.223 pH 7 2.24 pH 9 8.83 Solvent solubility (g/L at 25oC) Acetone

- 11.9 Acetonitrile

- 7.3 Dichloromethane

- 27.5 Ethanol

- 0.9 Ethyl acetate

- 2.6 Hexane

- <0.1 Methanol

- 2.6 Xylene

- 0.2 Vapor pressure (25oC) 1.7 x 10

- 8 Pa (1.3 x 10

- 10 mm Hg) Dissociation constant (pK a ) 4.0 Octanol/water partition coefficient (Log [K OW ]) pH 5 1.06 pH 7 0.0222 pH 9 0.0078

### Page 36 of 37

Appendix F. Spray Drift Detailed Description

Off

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

. Sprays that are released and do not deposit in the application area end up off

target and can lead to exposures to tho se the chemical may directly contact

. Sprays can also deposit on surfaces where individuals come into contact with residues on these surfaces, lead ing to indirect exposures (e.g., children playing on lawns where residues have deposited next to treated fiel ds).

The approach to be used for quantitatively incorporating spray drift into risk assessment is based on a premise of compliant applications which, by definition, should not result in direct exposures to individuals because of existing label language an d other regulatory requirements intended to prevent them 11



### . [ Direct exposures would include inhalation of the spray plume or being sprayed directly. ] Rather, the exposures addressed here are thought to occur indirectly through contact with impacted areas, such as residential lawns, when compliant applications are conducted

. Given this premise, exposures for children (1 to 2 years old) and adults who h ave 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 t he drift potential and associated risks, an approach based on drift modeling coupled with techniques used to evaluate residential uses of pesticides was utilized

. Essentially, a residential turf assessment based on exposure to deposited residues has been c ompleted to address drift from the agricultural applications of thifensulfuron methyl

. In the spray drift scenario, the deposited residue value was determined based on the amount of spray drift that may occur at varying distances from the edge of the treat ed 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 w as 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 t hat defines application parameters is not available 12 13



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

. When AgDrift was developed, a series of screening values (i.e., the Tier 1 option) were incorporated into the model and represent each equipment type and use under varied conditions

. The screening options specifically recommended in this methodology were selected because they are plausible and represent a reasonable upper bound level of drift for common application methods in agriculture

. These screening options are consistent with how spray drift is considered in a number of ecological risk assessments and in the process used to develop drinking water concentrations used for ri sk assessment

. In all cases, each scenario is to be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are

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

12 h ttp://www.agdrift.com/
13 Note that for many cases the scenarios outlined in the screening approach represent actual use practice so risk assessors should be aware and characterize these appropriately.

### Page 37 of 37

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

. 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 prov ide additional risk management options additional spray drift deposition fractions were also considered

. These drift estimates represent plausible options for pesticide labels

.