Page 3 of 18

Introduction

HED has evaluated the mo st recent human health risk assessment ( D3 88621 ) for triflusulfuron

- methyl to determine whether sufficient data are available and whether a new human health risk assessment is needed to support Registration Review. HED has considered the most recent risk assessment s for triflusulfuron

- methyl

, updates to its toxicity, exposure and usage databases, and current Agency science policies and risk assessment methods.

Use Profile

Triflusulfuron

- methyl is a sulfonylurea herbicide, registered by E. I. du Pont de Nemours and Company

, that inhibits the biosynthesis of branched

- chain amino acids in plants (via inhibition of the plant enzyme acetolactate synthase). Marketed as UpBeet®, a dry flowable (DF) formulation containing 50% active ingredient (ai), triflusu lfuron

- methyl is currently registered for use on sugar beet commodities, garden beets, and chicory using broadcast (ground

- or aerial

based) or band application methods at seasonal rates of up to 0.078 pounds ai per acre (lb ai/A). UpBeet® is not to be ap plied via any type of irrigation system. The existing label for UpBeet® lists a pre

- harvest interval (PHI) of 60 days for sugar beet, garden beet, and chicory. There are no current or pending residential uses associated with triflusulfuron; therefore, a re sidential exposure assessment was not performed nor required.

The chemical structure and nomenclature of triflusulfuron

- methyl are presented in Table 1. The physicochemical properties of the technical grade of triflusulfuron

- methyl are presented in Append ix 1, Table 1 of the Appendix.

TABLE 1. Triflusulfuron

- Methyl Structure and Nomenclature.

Compound Chemical Structure

Common name Triflusulfuron

- methyl Company experimental name DPX 66037

IUPAC name methyl 2

- [4

- dimethylamino

- 6

- (2,2,2

- trifluoroethoxy)

- 1,3,5

- triazin

- 2

- ylcarbamoylsulfamoyl]

- m

- toluic acid

CAS name methyl 2

- [[[[[4

- (dimethylamino)

- 6

- (2,2,2

- trifluoroethoxy)

- 1,3,5

- triazin

- 2

- yl]amino] carbonyl]amino]sulfonyl]

- 3

- methylbenzoate

CAS # 126535

- 15

- 7

End

- use product/(EP) UpBeet HerbicidePage 4 of 18

Hazard Identification/Toxicology

The primary target organs of toxicity identified for triflusulfuron

- methyl are the liver, testes and red blood cells. Hematological and histopathological changes consistent with mild hemolytic anemia were observed in the rat and the dog. Increased incidence of testicular interstitial hyperp lasia was observed following subchronic or chronic

- term dietary administration to the rat; the incidence of testicular interstitial adenomas was also increased with chronic exposure. In the dog, testicular atrophy and reduced size were observed following subchronic or chronic exposure. Liver effects were observed in the dog (increased weight, altered serum enzyme profile and histopathology) and mouse (increased weight and histopathology), but not in the rat. There was no indication of frank neurotoxicity in the available studies , including the acute and subchronic neurotoxicity studies . Although a statistically significant increase in sciatic nerve myelin/axon degeneration in high dose female rats was observed in the rat combined chronic toxicity/carcino genicity study, the incidence was high in all dose groups , no increases were seen in the interim sacrifice groups or in shorter

- term studies and the lesion is commonly observed in older rats. Therefore, HED did not consider this finding to be evidence of frank neurotoxicity. A developmental neurotoxicity (DNT) study is, therefore, not required. The only potential evidence of immunotoxicity observed for triflusulfuron

- methyl was hemolytic anemia, an effect that is associated with exposure to some sulfony lurea compounds as an immune

- mediated cytotoxicity. However, there are currently no data demonstrating that hemolytic anemia from triflusulfuron

- methyl is immune

- mediated. No effects of treatment were reported in a 21

- day repeated application dermal toxi city study in the rabbit. Dermal absorption studies were not submitted.

Triflusulfuron

- methyl is of low acute toxicity when administered orally (Toxicity Category IV), dermally (Category III), or via inhalation (Category IV). It is not a dermal sensitiz er or irritant (Category IV) and causes only minor transient irritation to the eye (Category III).

There was no quantitative or qualitative evidence of increased pre

- and/or post

- natal susceptibility in rat or rabbit developmental toxicity studies or in t he rat reproductive study . No developmental effects were seen in the rat developmental stud y, whereas maternal toxicity (decreased body weight gain, food consumption and feed efficiency) was observed at the highest two doses. Abortions were observed in t he rabbit developmental toxicity study at a dose that also caused significant maternal toxicity, including mortality, clinical signs, sharply reduced food consumption and decreased weight gain. In the rat reproductive toxicity study, decreased parental bo dy weight/weight gain and F1 pup weight during lactation were observed at the mid and high doses. No reproductive effects were observed.

In metabolism studies conducted in the rat, triflusulfuron

- methyl was well

- absorbed and extensively metabolized; howe ver, at high doses, the extent of absorption was somewhat lower and the parent compound was the major radiolabeled component. The majority of the administered radioactivity was excreted in the urine at low doses, but at high doses, the major route of excr etion was the feces. The major urinary metabolite was N

- desmethyl triflusulfuron

methyl.Page 5 of 18

Triflusulfuron

- methyl was classified as a “Group C” (possible human) carcinogen under the 1986 Agency Guidelines for Carcinogen Assessment. The classification was b ased on an increased incidence of testicular interstitial cell adenomas in male rats at two doses and evidence of clastogenicity in some in vitro genotoxicity studies. A special mechanistic study that evaluated hormonal changes in male rats provided insuf ficient information to establish a nonlinear mode of action for the formation of these tumors. Although the incidence of hepatocellular adenomas was increased in mice, it was within historical control range and not considered as part of the weight

- of

- evid ence for determination of cancer classification. Cancer risk was not quantified using a cancer potency factor because the tumors were benign and seen only in one species; the use of the reference dose (RfD) in risk assessment was therefore considered to b e protective of potential carcinogenicity.

Studies available for the risk assessment of triflusulfuron

- methyl include acute lethality (oral, dermal and inhalation routes); primary eye and dermal irritation, dermal sensitization, subchronic oral toxicity ( rat, mouse and dog), rabbit 21

- day dermal toxicity, dog chronic toxicity, rat chronic toxicity and combined chronic toxicity/carcinogenicity, mouse carcinogenicity, developmental toxicity (rat and rabbit), rat two

- generation reproductive toxicity, genotoxi city, rat metabolism and acute and subchronic neurotoxicity studies in the rat. An in vitro mode of action study on hepatic aromatase activity and testosterone/estradiol levels in Leydig (interstitial) cells was also submitted. Summaries of these studies and endpoint selection are provided in Tables 3, 4 and 5 of Appendix 1

. Toxicity Data Requirement s

The immunotoxicity study is a new data requirement under 40 CFR Part 158 as a part of the data requirements for registration of a pestici d e (food and non

- food uses). A subchronic inhalation study is not available but is not required due to low use rates, low vapor pressure and high Margins of Exposure ( MOEs ) attained using an oral POD for assessing risks with handler
exposure ( HASPOC memo, TXR No. 00562 91 ).

Hazard Conclusions

E ndpoint selection and uncertainty factors may need to be re

- evaluated to ensure that points of departure reflect current policy. The Agency believes the existing database is adequate for risk

assess ment

. Dietary and Drinking Water Exposure

The most recent dietary exposure and risk assessment was performed in conjunction with the April 201 1 human

- health risk assessment conducted by HED (D3 88621

, E

. Holman

, et al. ; 13

- APR

- 201 1 ). An acute dietary assessment was not performed be cause no appropriate endpoint was available to determine the aRfD for the general population or any population subgroup. An unrefined chronic dietary exposure and risk assessment was performed using 100% CT for all crops; tolerance

- level residues, and DEE M

- FCID TM software. Dietary risk estimates were determined considering exposures from food plus drinking water using estimated drinking waterPage 6 of 18

concentrations (EDWCs) for ground water sources provided by the Environmental Fate and Effects Division (EFED).

The resulting chronic dietary risk estimates for food and drinking water combined are below HED’s LOC [i.e., <100% of the chronic population

- adjusted dose (cPAD) of 0.02 44 mg/kg bw/day] for the overall U.S. population and all population subgroups. Using DEEM

- FCID

, dietary risk is estimated at <1 % of the cPAD for the U.S. population and all populations subgroups. Potential d ietary cancer risk concerns due to long

- term consumption of triflusulfuron

- methyl residues are adequately addressed by the chronic exposure analysis using the cPAD.

EFED has provided Tier II EDWCs for use in drinking water assessments when triflusulfuron

methyl is used according to registered labeling on sugar beets (Memo, J. Melendez

, 22

- JUL Y

2010; DP# 37 3494 ). Because monitoring data are unavailable, estimates of triflusulfuron

- methyl concentrations were made only with models. The models PRZM/EXAMS were used to conduct surface water exposure assessments and SCI

- GROW for groundwater exposure assessments

. EDWCs were generated for the total residues of concern for risk assessment; parent triflusulfuron

- methyl . The highest estimated drinking water concentration w as associated with the groundwater estimate . Water residues ( ground water EDWC of 0. 0005 ppm) were incorporated in DEEM

- FCID TM into the food categories “water, direct, all sources” and “water, indirect, all sources” for the chronic assessment.

Conclusions The dietary

- exposure database is adequate to support the existing registr ations. HED has assessed dietary exposures. Risks from these exposures, including aggregate exposures, are below the level of concern. However, a new dietary exposure and risk assessment may be required during Registration Review to incorporate potentia l changes to the triflusulfuron

- methyl toxicological PODs and EDWCs

. In addition, the assessment would likely include updated

c onsumption information and utilize the newest version of DEEM

- FCID.

Tolerances and International Harmonization The residue chem istry database is complete to support the currently registered uses. Sugar beet metabolism data are sufficient to support the registered uses of triflusulfuron

- methyl. The metabolism of triflusulfuron

- methyl in ruminants is adequately understood. Confin ed rotational crop studies were conducted using wheat, beetroot (red beet), and lettuce, using triflusulfuron

methyl labeled in each ring (in separate studies). The tolerance expression should include only the parent compound, triflusulfuron

- methyl. The current tolerance expression is in concert with recent guidance ( Knizner, 2009 1 )

. At this time, no tolerances are required for residues of triflusulfuron

- methyl in livestock commodities. Suitable analytical methods are available to enforce tolerances for residues of triflusulfuron

- methyl. The residue definition of triflusulfuron

me thyl is presented in Table 2 of the Appendix. T he tolerance expression is up to current standards

.

1 Knizner, S. 2009. “Interim Guidance on Tolerance Expressions.” EPA Memorandum, May 27, 2009.Page 7 of 18

Occupational and Residential Exposure

The most recent occupational and residential exposure (ORE) assessment was performed in conjunction with the April 2 01 1 human

- health risk assessment for use on garden beet (D3 88621

, E

. Holman

, et al. ; 13

- APR

- 201 1 ). Triflusulfuron

- methyl is currently registered for use on sugar beet commodities, garden beets, and chicory, marketed as UpBeet®, a dry flowable (DF) formula tion containing 50% active ingredient. UpBeet® is labeled to be applied as broadcast (ground

- or aerial

- based) or band application methods at seasonal rates of up to 0.078 pounds ai per acre (lb ai/A) with applications made in 5

- 10 day intervals; not to b e applied via any type of irrigation system. The existing label for UpBeet® lists a pre

- harvest interval (PHI) of 60 days for sugar beet, garden beet, and chicory. For sugar beet, UpBeet may be broadcast applied via ground or air equipment at up to 0.032 lb ai/A/application. For chicory, the maximum single application rate is 0.024 lb ai/A, with a maximum seasonal application rate of 0.048 lb ai/A. For garden beets, the maximum single application rate is 0.0156 lb ai/acre.

Non

- Cancer Inhalation Handler and Post

- Application Exposure Results The i nhalation handler exposure assessment resulted in MOEs greater than 1 00 which is the level of concern (LOC) for this chemical based on its toxicologic database, and, therefore, is not of

concern. A quantitative post

- application inhalation exposure assessment was not performed for triflusulfuron

- methyl because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure ( less than 1.0 x 10 - 7 mm Hg), and the low application rate (0. 032 lb ai/A). However, there are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resus pension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in Decem ber 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data gene rated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for triflusulfuron

- methyl

. Spray drift is always a potential source of exposure to residents nearby to spraying operations. This is particularly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from ground

– based applications of triflusulfuron

- methyl. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the Agency’s Spray Drift website for more information at http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by chemical basis, the Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling. Othe r potential sources of residential exposure include volatilization of pesticides and re

- suspension of dusts and/or particulates that contain pesticides.Page 8 of 18

Non

- Cancer Dermal Handler and Post

- Application Exposure Results No systemic toxicity was seen at the limit dose (1000 mg/kg/day) of a 28

- day dermal toxicity study in the rabbit. Therefore, neither a quantitative dermal handler nor post

- application exposure assessment was performed.

Residential Exposure There are no current or pending residential uses associated with triflusulfuron; therefore, a residential exposure assessment was not performed nor required.

Cancer Risk Triflusulfuron

- methyl is a Group C (1986 Cancer Guidelines

- possible human carcinogen) chemical, based on increased incidence of tes ticular cell adenomas in rats . The study on which the chronic reference dose (RfD) is based is considered to be adequately protective of these effects.

Restricted Entry Interval T he restricted entry interval (REI) is based on the acute toxicity of triflusulfuron

- methyl technical material . T riflusulfuron

- methyl is classified as Toxicity Category III by the dermal route, Toxicity Category IV for eye irritation potential, and Toxicity Category IV for skin irritation potential

. Under the Worker Protec tion Standard for Agricultural Pesticides, active ingredients classified as acute toxicity categories III or IV for these routes are usually assigned a 12

- hour REI. However, triflusulfuron

- methyl meets the criteria in PR Notice 95

- 3 for low risk pesticide s that are permitted to have a 4

- hour REI. Therefore, HED has no objections to the 4

- hour REIs on the existing registered label (for sugar beet and chicory uses) and the proposed supplemental label for garden beet. In addition, no dermal endpoints were i dentified, therefore

, dermal post

- application risks are not anticipated.

Conclusions for Residential and Occupational Exposure Since there are no currently registered residential uses for triflusulfuron

- methyl, it is not anticipated that a residential ass essment will need to be conducted during registration review. Due to recent occupational exposure science policy updates, existing occupational scenarios may have to be reassessed . These updates include changes to data sources and default assessment inpu ts for both occupational handler and post

- application assessments. In addition, the assessment may need to be updated to reflect any potential changes to the points of departure (PODs) or uncertainty factors for triflusulfuron

- methyl.

Aggregate Exposure

Since there are no residential exposures to triflusulfuron

- methyl

, a ggregate exposure is equal to the dietary exposure from food and water.

Incident Report

The OPP Incident Data System (IDS) was utilized to retrieve pesticide incident data on the active ingredient triflusulfuron

- methyl

. Based on the low frequency and severity of incident cases reported for triflusulfuron

- methyl , there does not appear to be a concern at this time that wouldPage 9 of 18

warrant further investigation (D399193) . The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be included in the risk
assessment.

Endocrine Disruption

As req uired by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, de velopmental, 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, fe rtility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part o f its reregistration decision

, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), triflusulfuron

- methyl is subject to th e endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

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

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estr ogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which , if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

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

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

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

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 in ert ingredients. T riflusulfuron

methyl is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call

- ins, requiring th e submission of EDSP screening assays for triflusulfuron

methyl

. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

.

C umulative

EPA does not have, at this time, available data to determine whether triflusulfuron

- methyl has a common mechanism of toxicity with other substances. EPA has not made a commonPage 10 of 18

mechanism of toxicity finding for triflusulfuron

- methyl and any other substances and, triflusulfuron

- methyl does not appear to produce a toxic metabolite produced by other substances which have tolerances in the U. S. Therefore, EPA has not assumed that triflusulfuron

- methyl has a common mechanism of toxicity with other substances.

Human Studies

The occupa tional exposure and risk assessment for triflusulfuron

- methyl relied in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These studies required a review of their ethical conduct and have received the appropriate review by the Human Studies Review Board (HSRB). Many such studies, involving exposure to many different pesticides, comprise generic pesticide exposure databases such as the PHED and the Agricultural Reentry Task Force (ARTF) Dat abase. EPA has reviewed all the studies in these multi

- pesticide generic exposure databases, and on the basis of available evidence has found them to have been neither fundamentally unethical nor significantly deficient relative to standards of ethical re search conduct prevailing when they were conducted. There is no regulatory barrier to continued reliance on these studies, and all applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in the human

- health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations,” (http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). The OPP typically considers the highest potential exposures from the legal use of a pesticide when conducting human

- health risk a ssessments, including, but not limited to, people who obtain drinking water from sources near agricultural areas, the variability of diets within the U.S., and people who might be exposed when harvesting crops. Should these highest exposures indicate pote ntial risks of concern, OPP further refines the risk assessments to ensure that the risk estimates are based on the best available information. Conclusions/Future Actions Needed

T he actions needed in the future Registration Review for triflusulfuron

- methy l are listed below

. Hazard Identification and Endpoint Selection

Based on the additional toxicity studies that are required , the toxicity database for triflusulfuron

methyl may need to be re

- evaluated. Specifically, endpoint selection and uncertainty factors
may need to be re

- evaluated to ensure that points of departure reflect current policy.

Dietary and Drinking Water Exposure and Risk The dietary and drinking water exposur e assessment s are adequate based on current methodologies. However, an updated assessment may be required during the registration review process to include any new data submitted as conditions of registration, revised points ofPage 11 of 18

departure (PODs) or uncerta inty factors or new drinking water data. The revised assessments should be conducted using the newest version of DEEM

- FCID which includes up dated consumption information.

Residential Exposure and Risk There are no current or pending residential uses associated with triflusulfuron

- methyl

. If residential uses are identified, then a r isk assessment needs to be conducted in accordance with current policies and SOPs

. Aggregate Exposure and Risk Since there are no residential exposures to triflusulfuron

- methyl

, a ggregate exposure is equal to the dietary exposure from food and water.

Occupation al Exposure and Risk The occupational exposure assessment may need to be updated to reflect current SOPs and to incorporate any new endpoints or uncertainty factors selected based on the required toxicity studies

. Incident Report Based on the absence of incident cases with triflusulfuron

- methyl , 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, additional analysis will be included in the risk assessment.

Data Requirements

Toxicity Data Requirements

The immunotoxicity study is a new data requirement under 40 CFR Part 158 as a part of the data requirements for registration of a pesticide (food and non

- food uses).

Residue Chemistry Data Requireme n ts

The residue chem istry database is complete to support the currently registered uses.

References

D388621: Triflusulfuron

- methyl: Revised Human Health Risk Assessment for Use in Garden Beet . April 13, 2011.

D 260076: Triflusulfuron

- methyl: Human Health Risk Assessment for the Section 3 Registration on Sugar Beets (PP#4F4278) and Chicory (PP#0E6214). Fe bruary 12, 2002.

D399193: Triflusulfuron

- methyl: Review of Human Incidents. May 3 , 2012

.

HASPOC memo. April 12, 2012. TXR No. 0056291

.Page 12 of 18 

### Attachments : Appendix 1Page 13 of 18

TABLE 1 Physicochemical Properties of the Triflusulfuron

- Methyl.

Parameter Value Reference

Melting point/range 155

- 158 o C Petition Administrative Materials

pH Not indicated

Density (g/mL) 1.45 absolute 0.56 (Bulk)

Water solubility ( 25°C) pH ppm 3 1.0 5 2.7 7 110 9 11 000 Low solubility at pH3 and pH 5; soluble at pH 7; very soluble at pH 9. Solubility increases with increasing pH.

Solvent solubility (mg/L) solvent mg/L hexane <0.0016 octanol 0.026 toluene 2.0 methanol 7.0 ethyl acetate 27 acetonitrile 80 acetone 120 chloroform 160 methylene chloride 580 Vapor pressure at 25°C <1 x 10 - 7 mm Hg
A relatively non

- volatile compound; low potential for losses due to volatilization.
Dissociation constant (pK a ) 4.4
This compound will dissociate and exist in its anionic form at most environmentally relevant pHs. Octanol/water partition coefficient (K OW ) pH K ow at 25°C 5 220 7 9.2 9 0.86 Low potential for bioaccumulation in biota.

UV/visible absorption spectrum λ max = 395 nm absorption at λ>400 nm is not anticipated
Potential to absorb sunlight in the UV/visible range of 290

- 400 nm.Page 14 of 18

Table 2. Residue Definition for Triflusulfuron

- methyl

Matrix Risk Assessment Tolerance

Plants Primary Crop Triflusulfuron

- methyl Triflusulfuron

- methyl

Rotational Crop Not applicable at this time Not applicable at this time

Livestock Ruminant Not applicable at this time Not applicable this time (under 40 CFR 180.6 (a)(3)) Poultry Not applicable at this time Not applicable at this time (under 40 CFR 180.6 (a)(3)) Drinking Water Triflusulfuron

- methyl Not ApplicablePage 15 of 18 Table 3. Toxic ity Data

Test Triflusulfuron

- methyl, Technical
Required Satisfied
870.1100 Acute Oral Toxicity

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

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

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

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

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

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

yes yes yes yes yes 870.3100 Oral Subchronic (rodent)

................................ ............... 870.3150 Oral Subchronic (nonrodent)

................................ ......... 870.3200 21

- Day Dermal

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

- Day Dermal

................................ .............................. 870.3465 90

- Day Inhalation

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

no

no yes

yes yes

-

- 870.3700a Developmental Toxicity (rodent)

................................ ... 870.3700b Developmental Toxicity (nonrodent)

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

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

yes yes 870.4100a Chronic Toxicity (rodent)

................................ .............. 870.4100b Chronic Toxicity (nonrodent)

................................ ........ 870.4200a Oncogenicity (rat)

................................ .......................... 870.4200b Oncogenicity (mouse)

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

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

yes yes yes yes 870.5100 Mutagenicity

— Gene Mutation

- bacterial

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

— Gene Mutation

- mammalian

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

— Structural Chromosomal Aberrations

... 870.5550 Mutagenicity

— Other Genotoxic Effects

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

yes yes yes 870.6100a Acute Delayed Neurotoxicity (hen)

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

- Day Neurotoxicity (hen)

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

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

- Day Neurotoxicity Screening Battery (rat)

............... 870.6300 Develop. Neurotoxicity

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

no yes yes

no --

-- yes yes

--
870.7485 General Metabolism

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

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

no ye s

no 870.7800 Immunotoxicity series

......................................................... yes no Special Studies for Ocular Effects

Acute Oral (rat)

................................ ........................... Subchronic Oral (rat)

................................ .................. Six

- month Oral (dog)

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

no

no --

--

--Page 16 of 18

Table 4 . Summary of Toxicological Doses and Endpoints for Triflusulfuron

- Methyl for Use in Dietary and Non

- Occupational Human Health Risk Assessments

Exposure/ Scenario Point of

Departure Uncertainty/FQP

A Safety Factors RfD, PAD,

Level of Concern for Risk Assessment Study and Toxicological Effects

Acute Dietary, General Population ( including Infants and Children and Females age 13 to 49) Not required. A n a ppropriate endpoint for this risk assessment w as not identified.

Chronic Dietary (All Populations) NOAEL=

2

. 44 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Chronic RfD =

0. 0244 mg/kg/day

cPAD = 0.0 244 mg/kg/day Chronic oral toxicity/carcinogenicity in

the rat LOAEL = 30.6 mg/kg/day, based on decreased body weight/weight gain, hematological changes (primarily males) and increased interstitial cell hyperplasia (males). Cancer (oral, dermal, inhalation) Classification: Group C (1986 Cancer Guidelines), based on increased incidence of testicular

interstitial cell adenomas in rats

. The RfD is considered adequately protective of these effects and a quantitative assessment of cancer risk using a cancer potency factor is not required. Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no obs erved adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a NOAEL. UF S = use of a short

- term study for long

- term risk assessment. UF DB = to account for the absence of key dat a (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.Page 17 of 18

T able 5. Summary of Toxicological Doses and Endpoints for Triflusulfuron

- Methyl 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 Short

Term (1 to 30 days) and Intermediate

Term (1 to 6 months) Not required. No toxicity was observed in the rabbit 21

- day dermal toxicity study up to the limit

dose of 1000 mg/kg/day.

Dermal Long

Term (> 6 months) Not required. Long

- term dermal exposure is not anticipated from current and proposed uses.

Inhalation Short

- Term (1 to 30 days) and Intermediate

Term (1 to 6 months) NOAEL =

6.56 mg/kg/day

(inhalation absorption
rate = 100%) UF A =10x

UF H =10x Occupational LOC

for MOE = 100 90

- day oral toxicity in the rat

LOAEL = 133 mg/kg/day (males)/153 mg/kg/ day (females), based on decreased body weight gain (observed after the first week of dosing) and body weight, and in females, extramedullary hematopoiesis.

Inhalation Long

- Term (> 6 months) Not required. Long

- term inhalation exposure is not anticipated from current and proposed uses.

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

interstitial cell adenomas in rats

. The RfD is considered adequately protective of these effects and a quantitative assessment of cancer risk using a cancer potency factor is not required. Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolat ion to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecie s). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a NOAEL. UF S = use of a short

- term study for long

- term risk assessment. UF DB = to account for the absence of key dat a (i.e., lack of a critical study). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.Page 18 of 18

T olerances and International Harmonization

International Residue Limits

No CODEX MRLs have been established for triflusulfuron

- methyl. The U.S. is in harmony with Canadian MRLs.

Triflusulfuron

- Methyl (PC Code 129002; Date of Request 4/12/12)

Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 40 CFR 180.492 Plant: triflusulfuron

- methyl (methyl 2

- [[[[[4

- (dimethylamino)

- 6

- (2,2,2

- trifluoroethoxy)

- 1,3,5

- triazin

- 2

- yl]amino]carbonyl]amino]sulfonyl]

- 3

- methylbenzoate) Livestock: NA methyl 2

- [4

- dimethylamino

- 6

- (2,2,2

- trifluoroethoxy)

- 1, 3,5

- triazin

- 2

- ylcarbamoylsulfamoyl]

- m

toluate None

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex Beet, garden, roots 0.01 Beet, garden, tops 0.02 Beet, sugar, roots 0.05 0.05 sugar beets Beet, sugar, tops 0.05 0.05 sugar beets Chicory, roots 0.05 0.05

MRLs with NO US equivalent Molasses 0.05 Sugar 0.05 Completed: M. Negussie; 04/1 3 /2012

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CC PR and the CAC.