UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 

### 20460

MEMORANDUM

Date: September 10

, 2015 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### SUBJECT: Triasulfuron. Draft Human Health Risk Assessment in Support of Registration Review.

PC Code: 128969 DP Barcode: D425587 Decision No .: 499901 Registration No.: NA Petition No

. : NA Regulatory Action: Registration Review Risk Assessment Type: Single Chemical A gg re ga te Case No.: 7221 TXR No.: NA CAS No.: 82087-50-5 MRID No.: NA 40 CFR: § 180.459



### FROM: Monica Hawkins

, Ph.D.

, M.P

. H.

, Risk Assessor/Environmental Health

# Scientist~4 Yung Yang

, Ph.D.

, Toxicologist 

### &/-,_ 6-· 

# 'L'-zr-

. - , ! Julie Van Alstine, M.P.H

., Envirorurllntal Healtn

### Scientist**~** V VVv

### ~ Risk Assessment Branch VI Health Effects Division (7509P)



### THROUGH: Donna S. Davis, Acting Branch Chief Risk Assessment Branch VI Health Effects Division (7509P)



### TO: Margaret Hathaway

, Chemical Review Manager Cathryn Britton

, Team Leader Kevin Costello, Branch Chief Risk Management and Implementation Branch 2 (RMIB 2) Pesticide Re-Evaluation Division (7508P) \

Since the last human health risk assessment and scoping do c ument, the following updates hav e been incorporated for triasulfuron.

1 ) The immunotoxicity and inhalation toxicity study requirements hav e b ee n waived (TXR# 0055323, TXR# 0056723

, TXR # 0052986). 2) Endpoints and points of departure have been selected for the incidental oral exposure scenario to assess spray drift exposure /

risk estimates

. 3) The occupational risk assessment ha s been updated to incorporate new science policies. 4) A refined-screening es timated drinking water conce ntration (E DW C) was used to assess triasulfuron dietary exposure and risk.

Pa ge 1 of29Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 2 of 29 Table of Contents

1.0 Executive Summary ............................................................................................................. 3 2.0 HED Recommendations....................................................................................................... 4 2.1 Tolerance Considerations ............................................................................................. .... 4 3.0 Introduction .................................................................................................................. ........ 4 3.1 Chemical Identity and Physica l/Chemical Characteristics ............................................... 4 3.2 Pesticide Use Pattern and Antic ipated Exposure Pathways ............................................. 4 3.3 Consideration of Environmental Justice .......................................................................... 6 4.0 Hazard Identification/Toxicology ........................................................................................ 6 4.1 Summary of Toxicological Effects ....................................................................................... 6 4.2 Safety Factor for Infants and Ch ildren (FQPA Safety Factor) ............................................. 7 4.3 Toxicity Endpoint and Point of Departure Selections .......................................................... 7 4.4 Endocrine Disruptor Screening Program ......................................................................... 9 5.0 Dietary Exposure and Risk Assessment .............................................................................. 9 5.1 Food Residue Profile ........................................................................................................ 9 5.2 Water Residue Profile .................................................................................................... 10 5.3 Dietary Exposure and Risk Estimates ............................................................................ 10 6.0 Residential (Non-Occupational) E xposure/Risk Characterization .................................... 11 6.1 Spray Drift ................................................................................................................... ... 11 6.1.1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications .............. 11

6.2 Residential Bystander Post-Appli cation Inhalation Exposure ....................................... 12 7.0 Aggregate Exposure/Risk Characterization ....................................................................... 13 8.0 Cumulative Exposure/Risk Characterization ..................................................................... 13 9.0 Occupational Exposure/Risk Characterization .................................................................. 13 9.1 Occupational Handler Expos ure/Risk Estimates............................................................ 13 9.2 Occupational Post-application Exposure/Risk Estimates ................................................... 15 9.3 Occupational Post-application Inhala tion Exposure/Risk Estimates .......................... 16

10.0 Public Health and Pesticide Epidemiology Data ............................................................... 17 11.0 Literature References ......................................................................................................... 17 12.0 References .................................................................................................................... ...... 18 Appendix A. Toxicology Data Requi rements and Toxicology Profile ......................................... 19 Appendix B. Review of Human Research ................................................................................... 22 Appendix C. Occupational Non-cancer Algorithms .................................................................... 23 Appendix D. Dietary Exposure/Risk Mode ling Input and Output ........................................... 25 Appendix E. Nomenclature and Physical/Chemical Properties .................................................... 27 Appendix F. Spray Drift Detailed Description ............................................................................. 28 Appendix G. Analytical Standards Summary .............................................................................. 29Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 3 of 29 1.0 Executive Summary

Triasulfuron is a sulfonylurea herbicide that is curre ntly registered for use in controlling broadleaf weeds on a variety of ag ricultural crops. It is currently registered for use on wheat, barley, pastures, and rangeland. This prelimin ary risk assessment (PRA) provides information to support the Registration Review of triasulfuron and addresses the exposures and risk estimates associated with all currently registered uses.

The toxicology database for tr iasulfuron is considered complete and adequate for risk assessment. The Hazard and Science Policy C ouncil (HASPOC) has waived the subchronic inhalation, immunotoxicity, and neur otoxicity (acute and subchroni c) studies for triasulfuron (TXR# 0055323, TXR# 0056723, TXR# 0052986). The last human health risk assessment for triasulfuron was completed in 2002 (D244111, D. Smeg al). Since then, no new toxicity and/or metabolism data have been received. For this assessment, the toxicol ogical endpoints and points of departure (PODs) have been updated to include a short-term oral endpoint in order to assess exposure from spray drift, and the short- and intermediated-term PODs were combined and updated for dermal and inhalation risk assessments . All other endpoints/PODs selected for risk assessment remain the same as in the previous assessments.

The existing residue chemistry database for tr iasulfuron is complete and adequate for risk assessment purposes. No additional residue ch emistry data are requi red at this time.

For dietary exposure, HED has conducted a chro nic dietary exposure and risk assessment for triasulfuron using tolerance-level residues in foods, 100% crop treated, and EDWCs provided by the Environmental Fate and Effects Division (EFED). Chronic diet ary exposure and risk estimates (food and drinking water) are not of concern and are 6.8% of the chronic population adjusted dose (cPAD) for the general U.S. population and 17% of the cPAD for children 1-2 years old, the most highly-exposed population subgroup. HED did not conduct an acute dietary exposure and risk assessment due to the lack of an appropriate endpoint for acute dietary assessment. Triasulfuron is classified as a Category E carcinogen with no evidence of carcinogenicity for humans; therefore, cancer ri sks are not of concer n for triasulfuron.

There are no registered residentia l uses or uses resulti ng in direct residentia l exposure associated with triasulfuron. Therefore, residential handler and conventi onal residential post-application exposure assessments were not conducted to supp ort Registration Review. A quantitative spray drift assessment was conducted. Risk estimates from groundboom and aerial applications are not of concern from the field edge for all scenar ios considered. During Registration Review, the agency will utilize the Volatili zation Screening Analysis to dete rmine if data (i.e., flux studies, route-specific inhalation toxicol ogical studies) or further analys is is required for triasulfuron.

In the case of triasulfuron, aggregate exposure an d risk estimates are equi valent to the dietary (food and water) exposure and risk estimates, an d do not exceed HED’s level of concern (LOC).

The occupational handler exposure and risk estimates based on the highest application rate and amount handled scenario indicate that the short- and intermed iate-term dermal and inhalation margins of exposure (MOEs) are not of concern to HED (i.e., MOEs ≥ the level of concern (LOC) of 100). The dermal and inhalati on MOEs ranged from 1,900 to 15,000. OccupationalTriasulfuron Human-Health Risk Assessment DP No. 425587

Page 4 of 29 post-application exposure and risk estimates indicate that the shor t- and intermediate-term MOEs are not of concern to HED on the day of application (i.e., MOE ൒ the LOC of 100). The MOEs ranged from 1,200 to 19,000. Based on the Agency's current practices, a quantitative non-cancer occupational post-application inha lation exposure assessment was not performed for triasulfuron. If new policies or procedures are put into place, the Agency may revisit the need for such an assessment for triasulfuron.

The restricted entry interval (R EI) of 4 hours specified on the regi stered labels is based on the acute toxicity of triasulfuron. Upon review of the criteria fo r the active ingredient only, it appears that triasulfuron is consistent with the criteria in PRN 95-3 that allow for a 4-hour REI. Note: The PR Notice also includes similar criteria for the end-use product. These criteria have not been evaluated by HED. Based solely on the active ingredient criteria, HED would recommend for reduction of the REI for triasulfuron.

This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. For a list of data sources see appendix B.

2.0 HED Recommendations

2.1 Tolerance Considerations

The existing tolerances for residues of tr iasulfuron (40 CFR §180.459) are supported by the available residue chemistry data. Codex has not established maxi mum residue limits (MRLs) for residues of triasulfuron. Canada has established MRLs for tr iasulfuron which are harmonized with U.S. tolerances.

HED notes that the tolerance expression for tr iasulfuron in 40 CFR §180.459 requires revision to state the following:

(a) General. Tolerances are established for residues of tria sulfuron, including its metabolites and degradates, in or on the co mmodities in the table below. Compliance with the tolerance levels specified belo w is to be determined by measuring only triasulfuron (2-(2-chloroethoxy)- N -[[(4-methoxy-6-met hyl-1,3,5-triazin-2- yl)amino]carbonyl]benzenesulfonamide) in or on the commodity.

3.0 Introduction

3.1 Chemical Identity and Phys ical/Chemical Characteristics

Triasulfuron (2-(2-chloroethoxy)- N -[[(4-methoxy-6-methyl-1,3,5-triazin-2- yl)amino]carbonyl]benzenesulfonamide) is a selectiv e herbicide used for pre-emergence control of broadleaf and grassy weeds. The nome nclature and physical/chemical properties of triasulfuron are provid ed in Appendix E.

3.2 Pesticide Use Pattern and Anticipated Exposure PathwaysTriasulfuron Human-Health Risk Assessment DP No. 425587

Page 5 of 29 Triasulfuron is currently registered for use on wh eat, barley, pastures, and rangeland. There are several end-use product labels registered with triasulfuron as the activ e ingredient. These include water-dispersible granules in water-solubl e packet (WSP) formulations. The registered products are applied either with aerial or groundboom equipment. The single application rate of the registered uses for triasulfuron ranges from 0.026 to 0.027 lb ai/A.

Exposure Pathways

Individuals may be exposed to tr iasulfuron via their diet (food and drinking water). There are no registered uses for triasulfuron that will resu lt in direct non-dietary (i.e., residential and occupational) exposures. However, there is the potential for indi rect exposure (incidental oral and dermal) to triasulfuron relate d to spray drift. Both handler and post-application occupational exposure is also possible for triasulfuron. Ag ricultural workers may be exposed (dermal and inhalation) to triasulfuron during mixing, loading, and/or applying the herb icide as well as during post-application activities.

Based on the use pattern for triasulfuron, short- and intermediate-term dermal and inhalation exposures for occupational handlers and occupa tional post-application workers are expected; long-term exposures (greater than 6 months) are not anticipated. The tria sulfuron labels require handlers to wear baseline attire (i.e., a long sleeved shirt, long pants, shoes plus socks) and chemical-resistant gloves.

Table 3.2 provides a summary of the highest app lication rate of the registered uses for triasulfuron.

Table 3.2. Summary of Regi stered Uses of Triasulfuron.

Application Equipment Formulation Maximum Application
Rate REI Use Directions and Limitations

Wheat

Groundboom, Aerial Waterdispersible granule in

WaterSoluble Packets 0.027 lb ai/A 4 hours Do not apply this product through any type of

irrigation system.

Barley

Groundboom, Aerial Waterdispersible granule in

WaterSoluble Packets 0.026 lb ai/A 4 hours Do not apply this product through any type of

irrigation system.

Pastures, Rangeland

Groundboom, Aerial Waterdispersible granule in 0.027 lb ai/A 4 hours Do not apply this product through any type of

irrigation system.Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 6 of 29 Table 3.2. Summary of Regi stered Uses of Triasulfuron.

Application Equipment Formulation Maximum Application
Rate REI Use Directions and Limitations

WaterSoluble Packets

3.3 Consideration of Environmental Justice

Potential areas of environmental ju stice concerns, to the extent possi ble, were considered in this human health risk assessment, in accordance w ith U.S. Executive Order 12898, "Federal Actions to Address Environmental Just ice in Minority Populations an d Low-Income Populations," (http://epa.gov/complian ce/ej/resources/policy/ex ec_order_12898.pdf). As a part of every pesticide risk assessment, OPP considers a larg e variety of consumer subgroups according to well-established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption pa tterns are compiled by the U.S. Department of Agriculture (USDA) under the Na tional Health and Nutrition Exam ination Survey, What We Eat in America, (NHANES/WWEIA; 2003- 2008) and are used in pesticid e risk assessments for all registered food uses of a pesticide. These da ta are analyzed and categorized by subgroups based on age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate , non-dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated ar eas post-application are evaluate d. Further considerations are currently in development as OPP has committed re sources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietar y patterns among specific subgroups.

4.0 Hazard Identification/Toxicology

The toxicology database for tria sulfuron is complete and adequate for risk assessment. The Hazard and Science Policy Council (HASPOC) ha s determined that subchronic inhalation, immunotoxicity, and neurotoxi city (acute and subchronic) studies are not required at this time for triasulfuron (TXR# 0055323, TXR# 0056723, TXR# 0052986). No new toxicity and/or metabolism data have been received since the last risk assessment (D244111, D. Smegal ) . The toxicological endpoints and PODs have been updat ed to include a short-term oral endpoint for the purpose of assessing exposure from spray drif t, and the short and in termediate-term PODs were combined for dermal and inhalation risk assessments. All other endpoints/PODs selected for risk assessment remain the same as those used in the previous assess ment. See Appendix A.2 for the triasulfuron toxi cological profile.

4.1 Summary of Toxicological EffectsTriasulfuron Human-Health Risk Assessment DP No. 425587

Page 7 of 29 The most prevalent effect observed was decr eased body weight in rats and dogs. The major target organ in mice is the liver (centrilobular hepatocytomegaly); while the most sensitive toxicological finding is decreased body weights in rats. In dogs, prostate cystic hyperplasia was observed following chronic exposure. In rodent s, triasulfuron caused developmental effects (delayed skeletal maturation) and reproductive effects only at high doses that also induced maternal and/or parental toxicity. The HED Rf D/Peer Review Committee classified triasulfuron as a Category E carcinogen, no evidence of car cinogenicity for humans (TXR 0012651). There is no mutagenicity con cern for triasulfuron.

There is no concern for increased quantitative or qualitative susceptibility of the young following in utero and pre- and post-natal exposure to triasulfuron based on the results from developmental studies conducted with rats and rabbits, as well as a two-genera tion reproduction study conducted with rats..

In acute lethality studies, triasu lfuron has low toxicity via the or al, dermal, and inhalation routes of exposure (Category III and IV). It is non-irritating to the skin (Category IV), and it is not a skin sensitizer. It is slightly irritating to the ey e (Category III). The acute toxicity of triasulfuron is presented in Appendix A.2.

Triasulfuron is rapidly absorbed and excreted within 96 hours of dosing: 74-99% in urine and 2- 14% in feces. Elimination rates after repeated oral dosing were faster than after single dosing. Residue levels in tissue were < 0.1% of the admini stered dose. Metabolite patterns in urine, fecal and liver extracts show mainly the parent compound. The variety of minor metabolites include 12 urinary (6.6-8.1%) and 10 fecal (1.2- 2.9%) of the administered radioactivity, respectively. No significant differences in metabolite patterns between sexes.

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

HED has recommended that the 10x Food Quality Pr otection Act (FQPA) Safety Factor (SF) be reduced to 1X for triasulfuron. The toxicology da tabase is complete, there is no evidence of increased susceptibility, no concer ns/residual uncertainties with re gard to pre- and/or postnatal toxicity, and no concern for neur otoxicity. In addition, HED is confident that the dietary (food and drinking water) assessment does not underestim ate risk to the general U.S. population or any population subgroup.

4.3 Toxicity Endpoint and Poin t of Departure Selections

The toxicological endpoints/PODs have been updated to include a short-term oral endpoint, and the short and intermediated-term PODs were combined for dermal and inhalation risk assessments. Otherwise, the No Observed A dverse Effect Levels (NOAELs) and Lowest Observed Adverse Effect Levels (LOAELs) have not been revised from the previous risk assessment. The PODs selected for risk assessmen t are protective of the effects observed in the triasulfuron database. A summary of toxicological doses and e ndpoints used in the triasulfuron human health risk assessments is presented below.Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 8 of 29 Table 4.3.1. Toxicological Doses and Endpoint for Triasulfuron for Use in Dietary and Non-Occupational Human Health Risk Assessment Exposure/Scenario Point of Departure Uncertainty/FQPA Safety Factors RfD, PAD, Level of Concern for Risk Assessment Study and Toxicological Effects

Acute Dietary (All populations) N/A N/A N/A An appropriate endpoint attributable to a single exposure (dose) was not identified from oral toxicity studies including the developmental toxicity studies in rats and rabbits. Chronic Dietary (all populations) NOAEL = 1.2 mg/kg/day UF A = 10X UF H = 10X FQPA SF = 1X Chronic RfD = 0.01 mg/kg/day

cPAD = 0.01 mg/kg/day Chronic /CarcinogenicityMice (MRID 40728316) LOAEL = 129 mg/kg/day based on centrilobular hepatomegaly in male mice Incidental Oral (Short- Term) NOAEL=10 mg/kg/day UF A = 10X UF H = 10X FQPA SF = 1X Residential LOC for MOE= 100 Subchronic Toxicity-Rat (MRID 40271947) LOAEL=500 mg/kg/day based on decreased body weight and food intake in both sexes of rats. Cancer (oral, dermal, inhalation) Classification: Category E carcinogen, no ev idence of carcinogenicity for humans. A carcinogenic risk assessment for triasulfuron is not required. Point of Departure (POD) = A data point or an estimated point that is derived from observed dos e-response data and used to mark the beginning of extrapolation to determine risk associat ed with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. L OAEL = lowest observed adverse effect le vel. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adju sted dose (a = acute, c = chronic).

Table 4.3.2. Summary of Toxicological Doses and Endpoints for Triasulfuron for Use in Occupational Human Health Risk Assessments

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

Dermal exposure (short- and intermediated-term) Oral NOAEL = 10 mg/kg/day UF A = 10x UF H =10x Dermal Absorption = 100% Occupational LOC for MOE = 100 Subchronic Toxicity-Rat (MRID 40271947) LOAEL=500 mg/kg/day based on decreased body weight and food intake in both sexes of
rats.

Inhalation exposure (Short- & intermediate term) Oral NOAEL = 10 mg/kg/day UF A = 10x UF H =10x Inhalation Absorption = 100% Occupational LOC for MOE = 100 Subchronic Toxicity-Rat (MRID 40271947) LOAEL=500 mg/kg/day based on decreased body weight and food intake in both sexes of
rats.

Cancer (oral, dermal, inhalation) Classification: Category E carcinogen, no ev idence of carcinogenicity for humans. A carcinogenic risk assessment for triasulfuron is not required. Point of Departure (POD) = A data point or an estimated point that is derived from observed dos e-response data and used to mark the beginning of extrapolation to determine risk associat ed with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. L OAEL = lowest observed adverse effect le vel. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of concern.Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 9 of 29 4.4 Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its most rece nt re-registration deci sion for triasulfuron, EPA reviewed these data and select ed the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), triasulfuron is subject to the endocrine screening pa rt of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify any adverse endo crine-related effects cau sed by the substance and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pest icide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP scr eening was published on June 14, 2013 1 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disrupt ors. For further information on the status of the EDSP, the policie s and procedures, the lis ts of chemicals, future lists, the test guidelines and the Tier 1 screeni ng battery, please visit our website. 2

5.0 Dietary Exposure and Risk Assessment

5.1 Food Residue Profile

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

2 http://www.epa.gov/endo/Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 10 of 29 The existing residue chemistry database for tr iasulfuron is complete and adequate for risk assessment purposes. No additional residue chemistr y data are required at th is time. The nature of the residue in plants and animals is adequate ly understood. The residue of concern for risk assessment and tolerance enforcement is the parent compound only (Memo, R. Schmitt, 06/22/1989, PP#8F3658). HED has previously conc luded that Method AG-500B is acceptable to enforce tolerances (Memo, G. Kramer, 02/16/1994, D193754).

5.2 Water Residue Profile

Screening ground water-sourced drinking water e xposure estimates were generated with the Pesticide Root Zone Model for GroundWater (PRZM-GW; v.1.07) for use in the sulfonylurea (SU) dietary risk assessments. EFED initia lly provided coarse-screen estimates that should exceed the upper-bound chemical-specific EDWCs fo r any SU; however, for several of the SUs, the coarse-screen EDWCs resulted in dietary risk s of concern and EFED subsequently generated refined-screen EDWCs for these SUs. The a pplication inputs for the refined-screen EDWCs represent the maximum application rate pattern for the chemical, considering the maximum single application rate first, then the maximu m seasonal application rate, using usage data provided by BEAD if the labels do not provide a maximum seasonal rate. The modeled sorption coefficient is also chemical-specific. All ot her inputs, including the screening assumptions of stability to degradation and application every year , remained the same as for the coarse screen. The resulting refined-screen EDWCs from PRZM-G W can be used as a conservative estimate of exposure and are summarized in Tabl e 5.1 (G. Orrick, D427429, 8/12/15).

The chronic dietary assessment for triasulfuron used the refined-screen post-breakthrough mean value of 19 μg/L (0.019 ppm).

Table 5.1. PRZM-GW Refined-Screen EDWCs for Sulfonylureas. 1

Sulfonylurea (Use) PRZM-GW Scenario Max. Daily Conc. (μg/L) Post-breakthrou g h Mean (μg/L) Mean Breakthrough Time (years) Chlorsulfuron (non-ag areas) NC cotton 78 52 5.9 Halosulfuron-methyl (fallow) NC cotton 74 53 8.1 Nicosulfuron (rights-of-way) NC cotton 39 26 6.2 Prosulfuron (corn) NC cotton 15 13 12 Rimsulfuron (commercial areas) NC cotton 105 71 6.5 Triasulfuron (rangeland) NC cotton 21 19 16 Tribenuron-methyl (corn) NC cotton 35 23 6.1 Triflusulfuron-methyl (sugarbeet) FL citrus 23 20 9.5

1 The triasulfuron drinking wa ter estimates are in bold.

5.3 Dietary Exposure and Risk Estimates

HED has conducted a chronic dietary exposure an d risk assessment for triasulfuron using tolerance-level residues in foods, 100% crop tr eated, and EDWCs provided by EFED. Exposure and risk estimates were obtained from the Di etary Exposure Evaluation Model using the Food Commodity Intake Database (DEEM-FCID; vers ion 3.18). The model uses food consumptionTriasulfuron Human-Health Risk Assessment DP No. 425587

Page 11 of 29 data from the 2003-2008 National Health and Nu trition Examination Survey/What We Eat in America (NHANES/WWEIA) database, coupled with recipe files and residues in foods, to derive estimates of diet ary exposure and risk.

Generally, HED is concerned wh en chronic dietary exposure estimates exceed 100% of the chronic population adjusted dos e (cPAD). Chronic dietary ri sk estimates (food and drinking water) are not of concern for the general U.S. population or any ot her population subgroup (Table 5.3). The chronic exposure estimate is 6.8% of the cPAD for the general U.S. population and 17% of the cPAD for children 1-2 years old, the most highly-e xposed population subgroup. Because of the very conservative assumptions us ed in the analysis (tolerance-level residues, 100% crop treated, upper-bound modeled drinking wate r 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. HE D did not conduct an acute dietary exposure and risk assessment due to the lack of an appropriate endpoint for acute dietary assessment. Triasulfuron is classified as a Category E carcinogen with no evidence of carcinogenicity for humans; therefore, cancer risks are not of concern for triasulfuron.

Table 5.3. Summary of Chronic Dietary Exposure (Food and Drinki ng Water) and Risk for Triasulfuron 1

.
Population Subgroup Chronic Dietary
Dietary Exposure (mg/kg/day) % cPAD
General U.S. Population 0.000677 6.8 All Infants (<1 year old) 0.001330 13 Children 1-2 years old 0.001716 17 Children 3-5 years old 0.001250 13 Children 6-12 years old 0.000824 8.2 Youth 13-19 years old 0.000547 5.5 Adults 20-49 years old 0.000604 6.0 Adults 50-99 years old 0.000570 5.7 Females 13-49 years old 0.000581 5.8

1 Population with the greatest exposure is in bold. Exposure and risk estimates calculated using DEEM version 3.18.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no registered residen tial uses or occupational uses re sulting in residential exposure associated with triasulfuron. Therefore, a quan titative residential exposur e assessment for direct residential uses wa s not performed.

6.1 Spray Drift

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

6.1.1 Combined Risk Estimates from Lawn Deposition Adjacent to Applications

The spray drift risk estimates are based on an estimated deposited residue concentration as a result of the screening-level agricultural applic ation scenarios. Triasulfuron is used on wheat, barley, pastures, and rangeland and can be a pplied via groundboom and aerial equipment. The spray drift assessment was conducted using the hi ghest registered applic ation rate of 0.027 lbTriasulfuron Human-Health Risk Assessment DP No. 425587

Page 12 of 29 ai/acre for use on wheat. The recommended drif t 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 90 th percentile results.

 Aerial applications are based on the use of AgDrift ® Tier 1 aerial opt ion for a fine-tomedium spray type and a series of other parameters, which will be described in more detail below (e.g., wind vector assumed to be 10 mph in a downwi nd direction for entire application/drift event). 3

Dermal risk estimates have been evaluated for adu lts. Dermal and incidental oral risk estimates were evaluated for children (1 to < 2 years old) . The total applicable LOC is 100 so MOEs < 100 would be of concern. Children’s (1 < 2 years old) dermal and incident al oral risk estimates and adult dermal risk estimates from exposure to triasulfuron related to spray drift result in no risks of concern at the field edge for either groundboom or for aerial applications

. Results are presented in Tables 6.1.1 and 6.1.2 below.

Table 6.1.1. Adult Risk Es timates (MOEs) Related to Indirect Expo sure to Spray Drift for Triasulfuron for the Dermal Route of Exposure
Crop/Rate

Group Spray Type/ Nozzle Configuration Application Rate (lb ai/A) Estimated or Adjusted TTR (ug/cm2) Edge-of-Field

Dermal MOE

Wheat
Aerial Fine to Medium
0.027 0.00300105 3,800

Groundboom High Boom Very fine to Fine 5,300

Table 6.1.2. Children (1 < 2 years old) Risk Esti mates (MOEs) Related to Indirect Exposure to Spray Drift for Triasulfuron for Combined Route of Exposure
Crop/Rate

Group Spray Type/ Nozzle Configuration Application Rate (lb ai/A) Estimated or Adjusted TTR t (ug/cm2) Edge-of-Field

Combined MOE 1

Wheat
Aerial Fine to Medium 0.027 0.00300105 1,900

Groundboom High Boom Very fine to Fine 2,600

1. Dermal and incidental oral risks were co mbined for children 1 to < 2 years old.

6.2 Residential Bystander Post-Application Inhalation Exposure

Volatilization of pes ticides may be a source of post-ap plication inhala tion exposure to individuals nearby pesticide app lications. The agency sought expert advice and input on issues

3 AgDrift ® allows for consideration of even finer spray patterns characterized as very fine to fine. However, this spray pattern was not selected as the common screening basis since it is used less commonly for most agriculture. If assessors identify this use pattern, then it should be used as the screening criteria and deposition values associated with it ae provided in Table 1 below. Justification for including this spray quality should be included in any assessment based on specific label directions for its use.Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 13 of 29 related to volatilization of pesticides from its Federal Insec ticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (S AP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/ SAP/meetings/2009/120109meeting.html). The agency has evaluated the SAP report and has de veloped a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis. 4 During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is required for triasulfuron.

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 a nd all other exposures for which there is reliable information. In the case of triasulfuron, aggregate expos ure and risk estimates are equivalent to the dietary (food and water) exposure and risk estimates in Section 5, above, and are below HED’s LOC.

8.0 Cumulative Exposure/Ri sk Characterization

In 2015, EPA’s Office of Pesticide Programs rele ased a guidance document entitled, Pesticide Cumulative Risk Assessment: Fram ework for Screening Analysis [http://www.epa.gov/oppfead1/cb/csb_page /updates/2015/framework-for-screeninganalysis.html]. This document provides guidance on how to screen groups of pesticides for cumulative evaluation using a two-step approach beginning with the evaluation of available toxicological information and if necessary, follo wed 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 [chemical name] is a member (J. D’Agostino; D428798; 9/9/15). Although the SUs share some chem ical and toxicological characteristics, the toxicological database does not support a testable hypothesis for a common mechanism of action. No further mechanistic data are required and no further cumulative evaluation is necessary.

9.0 Occupational Exposure/ Risk Characterization

9.1 Occupational Handler Exposure/Risk Estimates

Based on current labeling, types of equipment, a nd techniques that can potentially be used, occupational exposure associated with handler activities (i.e., mi xing, loading, and applying) is expected from the registered use on wheat, ba rley, pastures, and range land. The quantitative exposure/risk assessment developed for occupationa l handlers is based on the scenarios listed in Table 9.1.1. Based on the use patterns (i.e., 1 application per season) and resistance management practices, occupational exposure from the registered food uses is expected to be short-term (1-30 days) and intermediate-ter m (1-6 months) and in duration. Long-term

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

. 5 Guidance For Identifying Pesticide Chemicals and Other S ubstances 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)Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 14 of 29 exposures (greater than 6 months ) are not anticipated. The regist ered labels require handlers to wear baseline attire and chemical resistant gloves.

Occupational Handler Exposur e Data and Assumptions

Application Rate : The highest application rate of the registered us es is listed in Table 3.2.

Unit Exposures: It is the policy of HED to use the best av ailable data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, include PHED 1.1, the AHETF database, the Outdoor Residential Exposure Task Force (ORETF) database, or other registrant-submitted occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended for use in pred icting handler exposure that are used in this assessment, known as “unit exposures”, are outlin ed in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 7 ” which, along with additional information on 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 area treated or amo unt handled is based on HED ExpoSAC Policy No. 9.1. Refer to Table 9.1.1. for these assumptions for each scenario.

Risk Estimate Equations : The algorithms used to estimate non-cancer exposure and dose for occupational handlers can be found in Appendix C.

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

The short- and intermediate-term dermal and inhalation risk estimates for the occupational handlers are greater than HED’s LOC (i.e., MOEs ≥ 100) at baseline for all scenarios, with MOEs ranging from 2,400 to 15,000. Table 9.1.1. pr ovides the worst-case scenarios for the registered uses for triasulfuron.

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

8 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.htmlTriasulfuron Human-Health Risk Assessment DP No. 425587

Page 15 of 29 Table 9.1.1. Occupational Sho rt-term/Intermediate-term Handler Ex posure and Risk Estimates for Triasulfuron.

Exposure Scenario Crop or Target 1 Baseline Dermal

Unit Exposure 2 Baseline Inhalation Unit Exposure 2 Maximum Application Rate 3 Area Treated

or Amount Handled Daily 4 Baseline Dermal Baseline Inhalation Total

Dose 5 MOE 6 Dose 5 MOE 6 MOE 7

μ g/lb ai μ g/lb ai lb ai/A Acres mg/kg/day LOC = 100 mg/kg/day LOC = 100 LOC = 100
Mixer/Loader Water dispersible granule in

watersoluble packet for

aerial application Wheat 9.8 (EC) 0.24 0.027 1,200 0.00398 2,500 0.0000973 100,000 2,400

Waterdispersible granule in

watersoluble packet for groundboom application Wheat 9.8 (EC) 0.24 0.027 200 0.000661 15,000 0.0000163 610,000 15,000

Applicator Aerial Application Wheat 2.08 (EC) 0.0049 0.027 1,200 0.000843 12, 000 0.00000199 5,000,000 12,000

Groundboom Application Wheat 78.6 0.34 0.027 200 0. 0053 1,900 0.000023 430,000 1,900
Flagger Flagger Wheat 11 0.35 0.027 350 0.0013 7,700 0.0000414 240,000 7,500 1 The worst-case scenarios for th e registered uses for triasulf uron are listed in this table. 2 “Based on the “Occupational Pesticide Handler Unit Exposure Surr ogate Reference Table”; Level of mitigation = Baseline except for aerial applicator which includes engineering controls. 3 Based on the currently registered labels (See Table 3.2). 4 Exposure Science Advisory Council Policy #9.1. 5 Dermal Dose = Dermal Unit Exposure ( μ g/lb ai) ) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre) × Area Treated or Amount Handled Daily (A or gal/day) x DAF (%) ÷ BW (80 kg). Inhalation Dose = Inhalation Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 kg). 6 Dermal MOE = Dermal NOAEL (10 mg/kg/day) ÷ Dermal Dose (mg/kg/day). Inhalation MOE = I nhalation NOAEL (10 mg/kg/day) ÷ Inhalation Dose (mg/kg/day). 7 Total MOE = NOAEL (10 mg/kg/day) ÷ Dermal Dose + Inhalation Dose.
9.2 Occupational Post-Application Dermal Exposure/Risk Estimates

Occupational post-application expo sure is expected based on the registered agricultural products for triasulfuron. In accordance with 40 CFR Part 158, dislodgeable foliar residue (DFR) data are required for all occupational (e.g., crop, nurser y, greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post-application exposure to foliage. HED developed a waiver policy for DFR studies. The MOEs from the assessment, using default values are evaluated. If those are 2 times higher than the LOC the DFR studies can be waived.

Since the highest estimated occupational post-application exposure using default DFR values for triasulfuron is minimal in comparison to the LO C (i.e., the calculated MOE is greater than 2Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 16 of 29 times higher than the LOC, MOE = 1,200 compared to the LOC of 100); EPA is waiving the 40 CFR Part 158 DFR data. In this instance, it is unlikely that chemical-s pecific DFR data would be needed to further refine exposure assessmen ts or would add appreciably to our overall understanding of the availabil ity of dislodgeable foliar pes ticide residues for triasulfuron.

Table 9.2.1 provides a summary of the anticipated post-applicati on activities and associated transfer coefficients for the worst-case scenar ios for the registered uses for triasulfuron.

Table 9.2.1. Anticipated Po st-Application Activities and Dermal Transfer Coefficients.

Proposed Crops Policy Crop Group Category Crop Height Foliage Density Transfer Coefficients (cm 2 /hr ) Activities

Wheat Cereal Grain Low Min/Full 70 Hand Weeding

Wheat Cereal Grain Low Min/Full 1,100 Scouting

Occupational Post-Application Non-Cancer Dermal Risk Estimates

The short- and intermediate-term post-application exposure scenario s associated with the highest uses for triasulfuron are summarized in Table 9.2.2. All scenarios resulted in MOEs greater than the LOC of 100 (ranging from 1,200 to 19,000) on day 0 (12 hours after application); and, therefore, are not of concern to HED. The re stricted entry interval (REI) specified on the registered labels is 4 hours. Table 9.2.2 provi des MOEs reflecting the worst-case scenarios for the registered uses for triasulfuron.

Table 9.2.2. Occupational Post-Application Non-Canc er Exposure and Risk Estimates for Triasulfuron.

Crop/Site Activities Transfer Coefficient

(cm 2 /hr) Application Rate (lb ai/A) DFR 1 Dermal Dose (mg/kg/day) 2 MOE 3

Short- and Intermediate-term Wheat Hand Weeding 70 0.027 0.08 0.001 19,000
Wheat Scouting 1,100 0.027 0.08 0.008 1,200

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 (80 kg). 3 MOE = POD (mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR (μg/cm 2 ) × TC × 0.001 mg/μg × 8 hrs/day × dermal

absorption factor (100 %)]  BW (80 kg).

9.3 Occupational Post-Application I nhalation Exposure/Risk Estimates

There are multiple potential sources of post-app lication inhalation exposure to individuals performing post-applicati on activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulat es that contain pesticides. The agency sought expert advice an d input on issues relate d to volatilization of pesticides from its Federal Insecticide, Fungicide , and Rodenticide Act Scie ntific Advisory Panel (SAP) in December 2009, and received th e SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SA P/meetings/2009/120109meeting.html). The agency has evaluated the SAP report and has developed a Vo latilization Screening Tool and a subsequentTriasulfuron Human-Health Risk Assessment DP No. 425587

Page 17 of 29 Volatilization Screening Anal ysis (http://www.regulations .gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the agen cy will utilize this analysis to determine if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is required for triasulfuron.

In addition, the Agency is continuing to eval uate the available post- application inhalation exposure data generated by the Ag ricultural 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 expos ure into the agency's risk assessments.

Although a quantitative occupational post-applic ation inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resultin g from application of pesticides outdoors is likely to result in higher exposure than post -application exposure. Therefore, it is expect ed that these handler inhalation exposure estimates would be protec tive of most occupatio nal post-application inhalation exposure scenarios.

Restricted Entry Interval

Triasulfuron is classified as Toxicity Category III or IV ba sed upon data for acute dermal toxicity, acute inhalation toxi city, primary skin irritation, a nd primary eye irritation. Upon review of the criteria for the ac tive ingredient only, it appears that triasulfuron is consistent with the criteria in PRN 95-3 that allow for a 4-hour REI. Note : The PR Notice also includes similar criteria for the end-use product. These criteria have not been evaluated by HED. Based solely on the active ingredient criteria, HED w ould recommend for reduction of the REI for triasulfuron.

10.0 Public Health and Pesticide Epidemiology Data

The OPP Incident Data System (IDS), the Center s for Disease Control and Prevention/National Institute for Occupational Safety and Health (C DC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) database s were consulted for pesticide incident data on the active ingredient tria sulfuron (S. Recore, 12/08/2011, D 396006). In Aggregate IDS and Main IDS, from January 1, 2006 to June 6, 2011 th ere was 1 incident i nvolving triasulfuron. Upon review of these incidents, it was concluded that “Based on the low frequency and severity of incident cases, there does not appear to be a concern at this time that would warrant further investigation.” An IDS analysis was conducted from June 2011 to February 25, 2015; no incidents (Aggregate or Main IDS) were reporte d for triasulfuron. Triasulfuron is not included in the Agricultural Health Study (AHS), and ther efore this study does not provide information for this report. The Agency will continue to mon itor the incident information and if a concern is triggered, additional analysis will be included in the risk assessment.

11.0 Literature References

A literature search was performed for triasulfuron. The search did not reveal information that would impact the current risk assessment.Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 18 of 29 12.0 References

Author Barcode Date Title P. Yvonne Barnes, M. Hawkins, Y. Yang D394284 2/28/2012 Triasulfuron: Human Health Assessment Scoping Document in Support of Registration Review

S. Recore D396006 12/13/2011 Triasulfuron: Review of Human Incidents D. Smegal, P. Hurley, M. Nelson, M. Collantes D244111 7/10/1998 Triasulfuron: Human Health Risk Assessment for Use on Grasses.

P. Barnes et al. D394284 02/28/2012 Triasulfuron: Registration Review Scoping Document for Human Health Assessments. R. Schmitt

-- 06/22/1989 New Chemical Review of Triasulfuron

G. Kramer D193754 02/16/1994 PP#3F04225. Triasulfuron in or on grass forage, fodder, and hay group. Evaluation of residue data and analytical methods. MRID#s 427716-01, 428519-01 and -02. Barcodes D193754 & D193756. CBTS#s 12818 & 12319. G. Orrick D427429 8/12/15 Drinking Water Exposure Assessment for the Registration Review of 22 Sulfonylurea HerbicidesTriasulfuron Human-Health Risk Assessment DP No. 425587

Page 19 of 29 Appendix A. Toxicology Data Requi rements and Toxicology Profile

The toxicology requirements (40 CFR 158.340) fo r triasulfuron are presented below.

Table A.1. Toxicology Data Re quirements for Triasulfuron

Test Technical
Required Satisfied
870.1100 Acute Oral Toxicity ....................................................... 870.1200 Acute Dermal Toxicity .................................................. 870.1300 Acute In halation Toxicity .............................................. 870.2400 Primar y Eye Irr itation

.................................................... 870.2500 Primar y Dermal Irr itation

.............................................. 870.2600 Derm al Sensiti zation ..................................................... yes yes yes yes yes yes yes yes yes yes yes yes

870.3100 Oral Su bchronic (rodent) ............................................... 870.3150 Oral Su bchronic (nonr odent) ......................................... 870.3200 21-Day Dermal .............................................................. 870.3250 90-Day Dermal .............................................................. 870.3465 90-D ay Inhala tion .......................................................... yes yes yes

no CR yes yes yes

- waived 1
870.3700a Developmental Toxicity (rodent) .................................. 870.3700b Developmental Toxicity (nonrodent) ............................ 870.3800 Reproduc tion ................................................................. yes yes yes yes yes yes

870.4100a Chronic T oxicity (rodent) .............................................. 870.4100b Chronic Toxi city (nonrodent) ........................................ 870.4200a Oncoge nicity (ra t) .......................................................... 870.4200b Oncogenicity (mouse) ................................................... 870.4300 Chroni c/Oncogeni city ................................................... yes

no yes yes yes yes

- yes yes yes 870.5100 Mutagenicity—G ene Mutation - bacterial ..................... 870.5xxx Mutagenicity—Struc tural Chromosomal Aberrations ... 870.5xxx Mutagenicity—O ther Genotoxic Effects ....................... yes yes yes yes yes yes 870.6100a Acute Delaye d Neurotox. (hen) ..................................... 870.6100b 90-Day Neurotoxicity (hen) .......................................... 870.6200a Acute Neurotox. Screening Battery (rat) ....................... 870.6200b 90-Day Neuro. Screening Batte ry (rat) ......................... 870.6300 Develop. Neuro ............................................................. no

no yes yes

no -

- waived 1 waived 1

-
870.7485 Gene ral Metabo lism ...................................................... 870.7600 Derm al Penetr ation ........................................................ 870.7800 Immunotoxicity............................................... yes

no yes yes

- Waived 1

1 HASPOC recommends that the 21-day dermal, subchronic inhalation toxicity , immunotoxicity, and neurotoxi city battery studies are not required at this time (TXR# 0055323, TXR# 0056723, TXR# 0052986).Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 20 of 29 A.2. Toxicity Profiles

Table A.2.1. Acute Toxicity Profile for Triasulfuron

OPPTS Guideline Study Type MRID
Number Results Toxicity Category

870.1100 Acute oral toxicity in Rats 40271931
40271930 LD 50 >5000 mg/kg IV

870.1200 Acute dermal toxicity
in Rats 40271932 LD 50 >2000 mg/kg III

870.1300 Acute inhalation toxicity
in Rats 40271933 LC50 >5.185 mg/L/4 hrs IV

870.2400 Acute eye irritation
in Rabbits 40271937 Mild conjunctival irritation, subsided by day 7 III

870.2500 Acute dermal irritation

In Rats 40271935 Very slight erythema and edema. IV

870.2600 Skin sensitization In Guinea Pigs 40271938 Negative NA

NA = Not applicable because a Toxicity Category is not assigned for this particular type of acute study.

Table A.2.2. Subchronic, Chronic and Ot her Toxicity Study for Triasulfuron

Guideline No./ Study Type MRID No. (year) Doses / Classification Results

870.3100 90-Day oral toxicity
rats 40271947 (1985) Acceptable/guideline NOAEL: 10 mg/kg/day LOAEL: 500 mg/kg/day based on decreased weight gain and food intake in both sexes. 870.3200 21-Day dermal toxicity rabbits 41585801 (1986) Acceptable/guideline NOAEL for irritation: 1,000 mg/kg/day NOAEL for systemic effects: not identified LOAEL for systemic effects: 10 mg/kg/day based on dyspnea, and ruffled fur that were not considered appropriate endpoints for human risk assessment. 870.3700a Prenatal developmental
rats 40271948 (1986) Acceptable /guideline Maternal NOAEL: 100 mg/kg/day Maternal LOAEL: 300 mg/ kg/day based on decreased body weight and decreased body weight gain during gestation. Developmental NOAEL: 300 mg/kg/day Developmental LOAEL: 900 mg/kg/day (HDT) based on reduced ossification of ve rtebrae, metatarsals and phalanges. 870.3700b Prenatal developmental rabbits 40271949 (1986) Acceptable/guideline Maternal NOAEL: 120 mg/kg/day Maternal LOAEL: 240 mg/ kg/day based on reduced maternal weight gain during gestation. Developmental NOAEL: >240 mg/kg/day (HDT) 870.3800 Reproduction and fertility effects
rats 40728317 (1987) Acceptable/guideline Parental NOAEL: 50 mg/kg/day Parental LOAEL: 250 mg/kg/ day based on significant decreases in premating and total body weight gain for F0 and F1 parental animals. Reproductive NAOEL: 50 mg/kg/day Reproductive LOAEL: 250 mg /kg/day (HDT) based on reduced F1a pup weights at birth and during lactation. 870.4100b 40271965 and 40542401(1986) NOAEL: 2.5 mg/kg/dayTriasulfuron Human-Health Risk Assessment DP No. 425587

Page 21 of 29 Table A.2.2. Subchronic, Chronic and Ot her Toxicity Study for Triasulfuron

Guideline No./ Study Type MRID No. (year) Doses / Classification Results

Chronic toxicity dogs Acceptable/guideline LOAEL: 25 mg/kg/day based on increased prostate cystic hyperplasia. 870.4300 Combined Chronic / Carcinogenicity

rats 40728318 and 41585802 (1987) Acceptable/guideline NOAEL: 32.1 mg/kg/day LOAEL: 220.8 mg/kg/day based on decreased mean body weight and decreased body weight gain. Negative for carcinogenicity.

870.4300 Carcinogenicity mice 40728316 (1988) Acceptable/guideline NOAEL = 1.2 mg/kg/day LOAEL: 129 mg/kg/day based on centrilobular hepatocytomegaly in males. There was no evidence of oncogenicity. Reverse gene mutation - Salmonella typhimurium 870.5100 40271951 (1983) Acceptable/guideline Strains TA 98, 100, 1535, 1537, 1538 tested at 0, 4, 16, 64, 256 μg/0.1 ml in absence and presence of metabolic activation. Negative up to cytotoxic concentrations, 64 and 256 μg/0.1 ml. Reverse gene mutation, recombination and gene conversion in Saccharomyces cerevisiae 870.5300 40271952 (1984) Provisionally Acceptable Strain D7 exposed to test article at 0, 46.9, 187.5,750, 3000 μg/ml in absence and presence of metabolic activation. Negative up to 3000 μg/ml. Deficiency: not tested up to limit concentration for negative study: 5000 μg/ml. Provisionally accep table pending toxicity test and new study at 5000 μg/ml. Forward gene mutation in mammalian cells: L5178Y/TK 870.5375 40271953 (1986) Acceptable Cells tested with and without metabolic activa tion at 0, 260, 520, 1040, 1560, 2080, 2340, 2600 μg/ml and 0, 300, 600, 1200, 1800, 2400, 2700, 3000 μg/ml, respectively. Negative up to levels of moderate cytotoxicity. In vivo cytogenicity study (micronucleus/Chinese hamsters) 40271954 (1984) Acceptable Administered orally to Chinese hamsters at 0, 625, 1250, 2500 mg/kg/day on each of 2 consecutive days. Negative for induction of micronuclei and/or other nuclear anomalies at doses reaching the limit dose: 5000 mg/kg (2500 mg/kg/day X 2). UDS study: DNA damage and repair in vitro in rat hepatocytes 40271955 (1984; 1986) (supplement) Acceptable Rat hepatocytes exposed to test substance at 0, 2, 10, 50, 250 μg/ml. Negative up to limit of solubility (250 μg/ml) for inducing UDS.

870.7485 Metabolism and pharmacokinetics 40728319 (1988) Acceptable/guideline Metabolism of [(U- 14 C)Phenyl]triasulfuron was studied in 5/sex Wistar rats. Material administered orally as a single low dose (0.5 mg/kg) & high dose (300 mg/kg), single low dose after daily doses of unlabeled material for 14 days (0.5 mg/kg/day) or single i.v. dose of 0.5 mg/kg. 92-109% of dose recovered within 96 hours: 74- 99% in urine & 2-14% in feces. Elimination rates after repeated oral dosing faster th an after single dose. Residue levels in tissue < 0.1%. Levels in tissues higher after single high dose than after single low dose. Even after repeated administration at low dose, no radioactivity retained by animals. Metabolite patterns in urine, fecal and liver extracts show main ly parent compound. Variety of minor metabolites: 12 urinary (6.6-8.1%), 10 fecal (1.2-2.9%) of the administered radioactivity, respectively. No significant differences in metabolite patterns between sexes.Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 22 of 29 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 receiv ed that review, and are complia nt 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/scien ce/post-app-exposure-data.html.Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 23 of 29 Appen dix C. Occupational Non-cancer Algorithms

Occupational Non-cancer Handler Algorithms

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

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

where:

E = exposure (mg ai/day), UE = unit exposure (μg ai/lb ai), AR = maximum application rate according to label (lb ai A or lb ai/gal), and A = area treated or amount ha ndled (e.g., A/day, gal/day).

The daily doses are calculated using the following formula:

ADD= E * AF
BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day), E = exposure (mg ai/day), AF = absorption factor (der mal and/or inhalation), and BW = body weight (kg).

Margin of Exposure: Non-cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), whic h is a ratio of the to xicological endpoint to the daily dose of concern. The daily dermal and inhalation dose received by occupational handlers are compared to the a ppropriate POD (i.e., NOAEL) to a ssess the risk to occupational handlers for each exposure route. All MOE values are calculated using the following formula:

MOE= POD
ADD

where:

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

Occupational Non-cancer Post -application Algorithms

Potential daily exposures for occupational post- application workers are calculated using the following formulas:Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 24 of 29 DFR t =AR * F* (1-D) t * ቀ 4.54E8 ug lb ቁ * ൬ 2.47E-8 A

cm 2 ൰

where:

DFR t = dislodgeable foliage residue on day "t" (μg/cm 2 ), AR = application rate (lb ai/acre), F = fraction of ai retained on foliage or 25% (unitless), D = fraction of residue that dissipa tes daily or 10% (unitless), and t = number of days afte r application day (days).

E=TC * DFR t * ET * 0.001 mg

ug

where: E = exposure (mg ai/day), TC = transfer coefficient (cm 2 /hr), DFR t = dislodgeable foliar re sidue on day “t” (μg/cm 2 ), and ET = exposure time (hours/day).

The daily doses are calculated using the following formula:

ADD= E * AF
BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day), E = exposure (mg ai/day), AF = absorption factor (der mal and/or inhalation), and BW = body weight (kg).

Margin of Exposure: Non-cancer risk estimates for each sc enario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxico logical endpoint to the daily dose of concern. The daily dermal dose received by occupational po st-application workers is compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational post-application workers. All MOE values are calculated using the following formula:

MOE= POD
ADD

where:

MOE = margin of exposure: value used by HE D 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).Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 25 of 29 Appendix D. Dietary Exposure/Ri sk Modeling Input and Output

DEEM-FCID Chronic Inputs File Filename: C:\Users\jlangsda\Documents\Chemicals\SUs\Triasulfuron\Dietary Assessment\Triasulfuron_Chronic.r08 Chemical: Triasulfuron RfD(Chronic): .01 mg/kg bw/day NOEL(Chronic): 0 mg/kg bw/day RfD(Acute): 0 mg/kg bw/day NOEL(Acute): 0 mg/kg bw/day Date created/last modified: 05-07-2015/10:31:54 Program ver. 3.16, 03-08-d

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

---------- ---- ------------------------------- ---------- ------ ------ ------- 1500025000 15 Barley, pearled barley 0.020000 1.000 1.000 1500025001 15 Barley, pearled barley-babyfood 0.020000 1.000 1.000 1500026000 15 Barley, flour 0.020000 1.000 1.000 1500026001 15 Barley, flour-babyfood 0.020000 1.000 1.000 1500027000 15 Barley, bran 0.020000 1.000 1.000 1500381000 15 Triticale, flour 0.020000 1.000 1.000 1500381001 15 Triticale, flour-babyfood 0.020000 1.000 1.000 1500401000 15 Wheat, grain 0.020000 1.000 1.000 1500401001 15 Wheat, grain-babyfood 0.020000 1.000 1.000 1500402000 15 Wheat, flour 0.020000 1.000 1.000 1500402001 15 Wheat, flour-babyfood 0.020000 1.000 1.000 1500403000 15 Wheat, germ 0.020000 1.000 1.000 1500404000 15 Wheat, bran 0.020000 1.000 1.000 3100044000 31 Beef, meat 0.100000 1.000 1.000 3100044001 31 Beef, meat-babyfood 0.100000 1.000 1.000 3100045000 31 Beef, meat, dried 0.100000 1.920 1.000 3100046000 31 Beef, meat byproducts 0.100000 1.000 1.000 3100046001 31 Beef, meat byproducts-babyfood 0.100000 1.000 1.000 3100047000 31 Beef, fat 0.100000 1.000 1.000 3100047001 31 Beef, fat-babyfood 0.100000 1.000 1.000 3100048000 31 Beef, kidney 0.500000 1.000 1.000 3100049000 31 Beef, liver 0.100000 1.000 1.000 3100049001 31 Beef, liver-babyfood 0.100000 1.000 1.000 3200169000 32 Goat, meat 0.100000 1.000 1.000 3200170000 32 Goat, meat byproducts 0.100000 1.000 1.000 3200171000 32 Goat, fat 0.100000 1.000 1.000 3200172000 32 Goat, kidney 0.500000 1.000 1.000 3200173000 32 Goat, liver 0.100000 1.000 1.000 3300189000 33 Horse, meat 0.100000 1.000 1.000 3400290000 34 Pork, meat 0.100000 1.000 1.000 3400290001 34 Pork, meat-babyfood 0.100000 1.000 1.000 3400291000 34 Pork, skin 0.100000 1.000 1.000 3400292000 34 Pork, meat byproducts 0.100000 1.000 1.000 3400292001 34 Pork, meat byproducts-babyfood 0.100000 1.000 1.000 3400293000 34 Pork, fat 0.100000 1.000 1.000 3400293001 34 Pork, fat-babyfood 0.100000 1.000 1.000 3400294000 34 Pork, kidney 0.500000 1.000 1.000 3400295000 34 Pork, liver 0.100000 1.000 1.000 3500339000 35 Sheep, meat 0.100000 1.000 1.000 3500339001 35 Sheep, meat-babyfood 0.100000 1.000 1.000 3500340000 35 Sheep, meat byproducts 0.100000 1.000 1.000 3500341000 35 Sheep, fat 0.100000 1.000 1.000 3500341001 35 Sheep, fat-babyfood 0.100000 1.000 1.000 3500342000 35 Sheep, kidney 0.500000 1.000 1.000 3500343000 35 Sheep, liver 0.100000 1.000 1.000 3600222000 36 Milk, fat 0.020000 1.000 1.000 3600222001 36 Milk, fat-baby food/infant formu 0.020000 1.000 1.000 3600223000 36 Milk, nonfat solids 0.020000 1.000 1.000 3600223001 36 Milk, nonfat solids-baby food/in 0.020000 1.000 1.000 3600224000 36 Milk, water 0.020000 1.000 1.000 3600224001 36 Milk, water-babyfood/infant form 0.020000 1.000 1.000 3600225001 36 Milk, sugar (lactose)-baby food/ 0.020000 1.000 1.000 3800221000 38 Meat, game 0.100000 1.000 1.000Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 26 of 29 3900312000 39 Rabbit, meat 0.100000 1.000 1.000 8601000000 86A Water, direct, all sources 0.019000 1.000 1.000 8602000000 86B Water, indirect, all sources 0.019000 1.000 1.000

DEEM-FCID Chronic Results File

U.S. EPA Ver. 3.16, 03-08-d DEEM-FCID Chronic analysis for TRIASULFURON NHANES 2003-2008 2-day Residue file name: C:\Users\jlangsda\Documents\Chemicals\SUs\Triasulfuron\Dietary Assessment\Triasulfuron_Chronic.r08 Adjustment factor #2 used. Analysis Date 05-07-2015/10:33:20 Residue file dated: 05-07-2015/10:31:54 Reference dose (RfD, Chronic) = .01 mg/kg bw/day

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

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

Total Exposure

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

-------------------------------------- ------------- ---------------- **Total US Population 0.000677 6.8%** Hispanic 0.000706 7.1% Non-Hisp-White 0.000684 6.8% Non-Hisp-Black 0.000574 5.7% Non-Hisp-Other 0.000749 7.5% Nursing Infants 0.000461 4.6% Non-Nursing Infants 0.001718 17.2% Female 13+ PREG 0.000595 6.0% Children 1-6 0.001389 13.9% Children 7-12 0.000778 7.8% Male 13-19 0.000573 5.7% Female 13-19/NP 0.000522 5.2% Male 20+ 0.000592 5.9% Female 20+/NP 0.000587 5.9% Seniors 55+ 0.000561 5.6% **All Infants 0.001330 13.3%** Female 13-50 0.000580 5.8% **Children 1-2 0.001716 17.2% Children 3-5 0.001250 12.5%**  **Children 6-12 0.000824 8.2% Youth 13-19 0.000547 5.5%**  **Adults 20-49 0.000604 6.0% Adults 50-99 0.000570 5.7%**  **Female 13-49 0.000581 5.8%**

-------------------------------------------------------------------------------Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 27 of 29 Appendix E. Nomenclature and Physical/Chemical Properties

Table E.1. Triasu fluron Nomenclature. Compound

Common name Triasulfuron Company experimental name Not Applicable IUPAC name 1-[2-(2-chloroethoxy)phenylsulfonyl] -3 - (4-methoxy-6- methyl-1,3,5-triazin-2- yl)urea, [3-(6-methoxy-4-methyl-1,3,5-triazin-2-yl)-1-(2-(2- chloroethoxy)phenylsulfonyl)urea] CAS name 2-(2-chloroethoxy)-N-[[(4 -methoxy-6-methyl-=1,3,5-triazin-2- yl)amino]carbonyl], benzenesulfonamide CAS registry number 82097- 50 - 5

Table E.2. Physicochemical Properties of the Technical Grade Triasulfuron. Parameter Value Reference Melting point/range 178°C/ Not Applicable Material Safety Data Sheet pH 6.0 -7.0 Density 0.50 – 70.0 g/cm3 Water solubility (mg/L) pH 5: 32 mg/l at 25 °C pH 7: 815 mg/l at 25 °C pH 8.4: 13500 mg/l at 25 °C Solvent solubility (mg/L) at room temperature N hexane 0.04 mg/l toluene 300 mg/l acetone 14 g/l n octanol 0.13 g/l ethyl acetate 4.3g/l dichloromethane 36g/l Vapor pressure < 1.5 x 10 (-8) mmHg @ 25°C (77°F) Dissociation constant, pK a 4.64 Octanol/water partition coefficient pH 5: log Pow =1.1 (at 25 °C) pH 6.9: log Pow = - 0.59 pH 9.0: log Pow = - 1.8 UV/visible absorption L mol -1 cm -1 223.4 nm ε 26051 l . mol -1 . cm -1 (purity 99.5 %) 282.8 nm ε 3415 l .mol -1 .cm -1 shoulder between 240nm - 250nm no absorption after 340 nmTriasulfuron Human-Health Risk Assessment DP No. 425587

Page 28 of 29 Appendix F. Spray Drift Detailed Description

Off-target movement of pesticides can occur vi a many types of pathways and it is governed by a variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly cont act. They can also deposit on surfaces where contact with residues can eventually lead to exposures (e.g

. , children playing on lawns where residues have deposited next to treated fields). Th e potential risk estimates from these residues can be calculated using drif t modeling coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorp orating spray drift into risk assessment include assessing exposures for children (1 to 2 years old) and adults w ho have contact with turf where residues are assumed to have deposited via spray drift thus resulting in an exposure scenario. Aside from the predicted residues available for transfer, the routes of exposure and assessment methodology is analogous to how exposures to turf products are considered in risk assessment.

In order to evaluate the drift potential and associ ated risks, an approach based on drift modeling coupled with techniques used to evaluate residential uses of pest icides was utilized. Essentially, a residential turf assessment based on exposure to deposited residues has been completed to address drift from the agricultural applications of triasulfuron. In the spray drift s cenario, the deposited residue value was determined based on the amount of spray drift that may occur at varying distances from the edge of the treated field using the AgDrift ® (v2.1.1) model. Exposures were considered for 50 feet wide lawn s where the nearest side of the property was directly adjoining the treated field (at field edge) and at va ried distances up to 300 feet downwind of a treated field. Once the deposited residue values were determined, the remainder of the spray drift assessment was based on the algorithms and i nput values specified in the recently revised (2012) Standard Operating Procedures For Residential Risk Assessment (SOPs)

. A screening approach was developed for situ ations where specific label guidance for application parameters is not available. 9,10 AgDrift ® is appropriate for use only when applications are made by aircraft, airblast sprayers , and groundboom sprayers. When AgDrift ® was developed, a series of screening va lues (i.e., the Tier 1 option) we re incorporated into the model and represent each equipment type and use unde r varied conditions. The screening options specifically recommended in this methodology were selected because they are plausible and represent a reasonable upper bound le vel of drift for common applic ation methods in agriculture. In all cases, each scenario is to be evaluated unl ess it is not plausible ba sed on the anticipated use pattern (e.g., herbicides are not t ypically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are not allowed). Section 6.1.1 provides th e screening level drift related risk estimates.

In many cases, risks are of concern when the screen ing level estimates for spray drift are used as the basis for the analysis. In order to account for this issue and to provide additional risk

9 http://www.agdrift.com/

10 Note that for many cases the scenarios outlined in the screenin g approach represent actual use practice so risk assessors shou ld be aware and characterize these appropriately.Triasulfuron Human-Health Risk Assessment DP No. 425587

Page 29 of 29 management options additional spray drift depositi on fractions were also considered. These drift estimates represent plausible options ba sed on the available pesticide labels.

Appendix G. Analytical Standards Summary

Analytical reference standards for triasulfuron are currently available in EPA’s National Pesticide Standards Repository (NPSR) and have an expiration date of 6/30/2017 (email communication between G. Verdin and J. Van Alstin e, 5/7/2015). The regi strant is required to maintain reasonable amounts of the reference sta ndards for triasulfuron in the NPSR as long as tolerances remain published in 40 CFR §180.459. Wh en 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 s hould be sent to the atte ntion of either Theresa Cole or Thuy Nguyen at the address listed be low, along with a letter of transmittal. Please note that the full 9-digit ZIP Code is required, or the mail will be returned to the registrant.

USEPA National Pesticide Standards Repository Analytical Chemistry Branch/BEAD/OPP 701 Mapes Road Fort George G. Meade, MD 20755-5350

The letter of transmittal should include the assay of the standard, name of the analytical method used, a statement of principal impurities, purification procedures employed, storage requirements, and special precautions for safe handling. Replacement of standards, or updated COAs, may be required periodically if supplies are exhausted, if the standards expire, or if decomposition occurs during storage. Material Safety Data Sheets (MSDSs) must accompany all analytical standards as specified by the Occupa tional Safety and Health Administration (OSHA) in 29CFR §1910.1200.