### Page 1 of 39 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDES, AND TOXIC SUBSTANCES 

### MEMORANDUM Date: 7 - AUG - 2009 SUBJECT: Triticonazole. Human Health Risk Assessment for Proposed Seed Treatment

Use on Cereal Grains (Crop Group 15) In cluding B arley , Field Corn, Oats, Popcorn , Rye, Sorghum Grain, Swe et Corn, Triticale, and Wheat (Excluding Rice) ; and Forage, Fodder, and Straw of Cereal Grains (Crop Group 16), Excluding Rice. PC Code: 125620 DP Barcode: 358614 Decision No.: 399232 Registration No. : 7969 - EIT Petition No.: 8F7420 Regulatory Action: Section 3 Registration Risk Assessment Type: Single Chemical/Aggregate Case No.: NA T XR No.: NA CAS No.: 131983 - 72 - 7 MRID No.: NA 40 CFR: 180. 58 3 FROM: N ancy

J. Tsaur, Risk Assessor Amelia Acierto, Chemist My ron Ottley , Toxicologist Risk Assessment Branch 3 (RAB3) Health Effects Division (7509P) THROUGH: Paula Deschamp, Branch Chief

Risk Assessment Branch 3 (RAB3) Health Effects Division (7509P) TO : Tony Kish/Bryant Crowe , Risk Management Team 22

and Cy nthia Giles - Parker, Branch Chief Fungicide Branch (FB) Registration Division (7505P)

### 2 of 39 Table of Contents INTRODUCTION ................................ ................................ ................................ ................................ ....................... 4 1.0 EXECUTIVE SUMMARY ................................ ................................ ................................ ........................... 6 2.0 SUMMARY OF PROPOSED USES ................................ ................................ ................................ ............ 9 3.0 HAZARD CHARACTERIZATION/ASSESSMENT ................................ ................................ .............. 10 3.1 Database Summary ................................ ................................ ................................ ................................ . 11 3.1.1 Sufficiency of studies/data ................................ ................................ ................................ ................. 11 3.1.2 Mode of action, m etabolism, toxicokinetic data ................................ ................................ .............. 11 3.1.3 Toxicological Effects ................................ ................................ ................................ .......................... 11 3.2 FQPA Considerations ................................ ................................ ................................ ............................. 12 3.2.1 Adequacy of the Toxicity Database ................................ ................................ ................................ .. 12 3.2.2 Evidence of Neurotoxicity ................................ ................................ ................................ ................. 13 3.2.3 Developm ental Toxicity Studies ................................ ................................ ................................ ........ 13 3.2.4 Reproductive Toxicity Study ................................ ................................ ................................ ............ 13 3.2.5 Additional Information from the Literature ................................ ................................ ................... 13 3.2.6 FQPA Safety Factor for Infants and Children ................................ ................................ ................ 13 3.3 Hazard Identification and Toxicity Endpoint Selection ................................ ................................ ...... 14 3.3.1 Leve l of Concern for Margin of Exposure/Population Adjusted Dose ................................ .......... 14 3.3.2 Recommendation for Aggregate Exposure Risk Assessments ................................ ....................... 14 3.3.3 Summary of Toxicological Doses and Endpoints for Triticonazole for Use in Hum an Risk Assessments ................................ ................................ ................................ ................................ ...................... 15 3.4 ENDOCRINE DISRUPTION ................................ ................................ ................................ ................ 17 4.0 PUBLIC HEALTH AND PESTICIDE EPIDEMIOLOGY DATA ................................ ........................ 18 5.0 DIETARY EXPOSURE/RISK CHARACTERIZATION ................................ ................................ ....... 18 5.1 Drinking Water Residue Profile ................................ ................................ ................................ ............ 18 5.2 Me tabolismin Primary Crops ................................ ................................ ................................ ............... 19 5.3 Me tabolismin Livestock ................................ ................................ ................................ ........................ 19 5.4 Analytical Methodology ................................ ................................ ................................ ......................... 20 5.5 Food Residue Profile ................................ ................................ ................................ .............................. 21 5.6 International Residue Limits ................................ ................................ ................................ ................. 22 5.7 Dietary Exposure and Risk ................................ ................................ ................................ .................... 23 6.0 RESIDENTIAL (NON - OCCUPATIONAL) EXPOSURE/RISK CHARACTERIZATION ................ 25 7.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION ................................ ..... 25 7.1 Acute Aggregate Risk ................................ ................................ ................................ ............................. 26 7.2 Short - Term and Intermediate - TermAggregate Risk ................................ ................................ ......... 26

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7.3 Long - Term Chronic Aggregate Risk ................................ ................................ ................................ .... 27 7.5 Cancer Aggregate Risk ................................ ................................ ................................ .......................... 27 8.0 CUMULATIVE RISK CHARACTERIZATION/ASSESSMENT ................................ ......................... 27 9.0 OCCUPATI ONAL EXPOSURE/RISK PATHWAY ................................ ................................ ............... 28 9.1 Short -/Intermediate - Term Handler Risk ................................ ................................ ............................ 28 9.2 Short -/Intermediate - Ter m Postapplication Risk ................................ ................................ ................. 31 10.0 DATA NEEDS AND LABEL RECOMMENDAT IONS ................................ ................................ .......... 31 10.1 Toxicology ................................ ................................ ................................ ................................ ............... 31 10.2 Residue Chemistry ................................ ................................ ................................ ................................ .. 32 10.3 Occupational and Residential Exposure ................................ ................................ ............................... 32 Appendix A: TOXICOLOGY ASSESSMENT ................................ ................................ ................................ ...... 33 A.1 Toxicology Data Requirem ents ................................ ................................ ................................ ............. 33 A.2 Acute Toxicity ................................ ................................ ................................ ................................ ......... 34 A.3 Toxicity Profile ................................ ................................ ................................ ................................ ........ 34 Appendix B: INTERNATIONAL RESIDUE LIMIT STATUS ................................ ................................ ........... 37 Appendix C: METABOLISM ASSESSMENT ................................ ................................ ................................ ...... 38

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INTRODUCTION The Health Effects Division (HED) has conducted a human health risk assessment for the fungicidal active ingredient (ai), triticonazole, for the purpose of a registration eligibility decision to establish tolerances for the seed treatment uses (cereal grains, except rice) requested b y the petitioner, BASF Corporation (BASF). Triticonazole is currently formulated for use as a seed treatment on barley

and wheat seeds (for which there are associated tolerances on barley and wheat commodities), as well as on turfgrass. BASF has submitted a petition (PP#8F7420) to register the end use product (EP) Triticonazole HL Fungicide Seed Treatment , a 43.5% ai (4.17 lbs ai/gallon) liquid flowable formulation of triticonazole (1 RS

) - ( E) - 5 - [(4 - chlorophenyl )methyl ene] - 2,2 - dimethyl - 1 - (1 H - 1,2,4 - triazol - 1 - yl methyl)cyclopentanol, for use in/on cereal grains (crop group 15, excluding rice) and forage, fodder, and straw of cereal grains (crop group 16, excluding rice) and proposed the following tolerances: Comm odity Proposed Tolerance (ppm) Grain, cereal, group 15 (except rice) 0.05 Grain, cereal, forage, fodder, and straw, group 16 (except rice) 0.10 

### HED recommends that a revised Section F be submitted to reflect the tolerance recommendation of 0.01 ppm for grain, cereal, group 15 (except rice); to reflect the tolerance recommendation of 0.25 ppm for grain, cereal, forage, fodder, and straw, group 16 (except rice); and to reflect the correct commodity definitions as listed in the tolerance summary below: Tolerance Summary for Triticonazole Commodity Established/Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity

Definition Established tolerances under 180.583(a) Barley, grain 0.05 Remove Barley grain will be covered with the establishment of the cereal grain, group 15 (except rice) tolerance. Barley, hay 0.05 Remove Increase in the tolerance based on residues resulting from new uses. Barley hay and straw and wheat forage will be covered with the establishment of the cereal grain group 16 (except rice) tolerance. Barley, straw 0.05 Remove Wheat, forage 0.05 Remove Wheat grain 0.05 Remove Wheat grain will be covered with the establi shment of the cereal grain, group 15 (except rice) tolerance Wheat, hay 0.05 Remove Increase in the tolerance based on

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Tolerance Summary for Triticonazole Commodity Established/Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity

Definition Wheat, straw 0.05 Remove residues resulting from new uses. Wheat hay and straw and will be covered with the establishment of the cereal grain group 16 (except ri ce) tolerance. Tolerances to be established under 180.583(a) Grain, cereal, group 15 (except rice) 0.05 0.01 NA Grain, cereal, forage, fodder, and straw , group 16 (except rice) 0.10 0.25 NA 

### The most recent prior human heal th risk assessment was conducted in conjunction with a request for use of triticonazole on turfgrass ( S. Winfield, DP#316612, 12/20/2006 ). The following information from the 12/20 /2006 risk assessment can be applied directl y to this action:

 Sections 2.2 - 2.3: Structure and Nomenclature, Physical and Chemical Properties,  Section 3.0: Hazard Characterization/Assessment, and  Sections 5.1.1 - 5.1.8: Pesticide Metabolism and Environmental Degradation. This document contains only those aspects of the risk assessm ent which are affected b y the proposed Section 3 request for use of triticonazole for seed treatments of the cereal grain crop groups (15 and 16), excluding rice. This document provides a summary of the findings from the data evaluation and subsequent as sessment of human health risk resulting from these requests. The hazard assessment and characterization were conducted b y M yron Ottley (RAB3), the residue chemistry data review and dietary

exposure assessment were completed by Amelia Acierto (RAB3), and the occupational residential exposure data review and human health risk assessment were performed by Nancy J. Tsaur (RAB3); additionally , the drinking water assessment was conducted by Cheryl Sutton of the Office of Pesticide Program ’s ( OPP’s ) Environmental Fate and Effects Division (EFED).

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1.0 EXECUTIVE SUMMARY Triticonazole is a triazole fungicide that is proposed for use as a seed treatment on cereal grains, except rice, for the control of various seed - borne plant diseases . As a triazole fungicide, th e contribution of triazole derivatives [1,2,4 - triazole, triazolylalanine, and triazolylacetic acid] from the use of triticonazole on cereal grains must be considered in the aggregate exposure for a triazole human health risk assessment . The requested seed treatment uses of triticonazole do not result in increases in dietary exposure estimates for free triazole or conjugated triazoles and thus, no updated risk assessments are needed for the triazole derivatives . Use Profile Triticonazole is currentl y reg istered and formulated for use as a seed treatment for barley and wheat, and for use in fungicidal products to control certain diseases of residential and commercial turfgrass, gol f courses, and sod farms. The proposed formulated end use product evaluated in this assessment is labeled under the trade name Triticonazole HL Fungicide Seed Treatment (liquid flowable containing 43.5% ai or 4.17 lbs ai/gallon). The proposed use rates for seed treatment range from 0.155 to 1.55 fl oz/100 lbs seed (0.005

– 0.05 lbs ai/100 lbs seed) . The formulation is to be applied once in a commercial seed treatment facility . Toxicity /Hazard Assessment Triticonazole has low acute toxicity, is not a skin, eye, or respiratory irritant, or a dermal sensitiz er . Dermal absorption was reported to be less than 2 %. N on - acute toxicity studies show that the liver (rat, mouse, dog) and adrenals (rat, dog, rabbit) are target organs across species . Adverse body

weight changes (rat, dog, rabbit, mouse) and clinical signs (rat, dog, mouse) also were observed in multiple species. In the developmental and reproductive toxicity studies, adverse effects on the offspring occurred onl y at dose levels which were toxic in the adults, and the offspring were not qualitatively more susceptible compared with adults. Inthe rat subchronic study , decreased thy

mus weight s were reported at a dose level (2309.3 mg/kg/day) two times higher than the limit dose (1000 mg/kg/day) . Triticonazole was negative for mutagenicity , and the cancer classification is “N ot Likely to Be Carcinogenic to Humans” based on a lack of evidence of carcinogenicity in the two guideline studies conducted on rats and mice . The nature and severity of toxicity

from triticonazole exposure are adequatel y characterized, and the no observ ed adverse effect levels (NOAELs ) and lowest observed adverse effect levels ( LOAELs ) established for the studies in the database are judged by HED to be adequately

protective for risk assessment purposes. Food Quality Protection Act (FQPA) Considerations There is a complete toxicity database for triticonazole , with the exception of a required immunotoxicity

study , and exposure is estimated based on data that reasonably account for potential exposures. There is no evidence of increased susceptibility follo wing in utero and/or postnatal exposure in the developmental toxicity studies in rats or rabbits, and in the 2 - generation rat reproduction study . There are no residual uncertainties concerning pre - and post - natal toxicity and no neurotoxicity

concerns. The acute and chronic dietary food and drinking water exposure assessments utilize screening - level and modeled residue values which will not underestimate exposures/risks. Based on these data and conclusions, the FQPA Safety Factor can be reduced to

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1X. Diet ary Exposure/Risk (food + water) Acute and chronic dietary exposure and risk assessments were conducted using the Dietary Exposure Evaluation Model (DEEM - FCID TM 

### , Version 2.03) which uses food consumption data from the U.S. Department of Agriculture’s Continuing Survey s of Food Intakes by Individuals (CSFII) from 1994 - 1996 and 1998. The proposed new uses do affect and add food commodities to the dietary

assessment but they

do not trigger new modeled estimated drinking water concentrations (EDWCs) of the 1 - i n - 10 year annual peak concentration of 75.5 ppb (for acute) and the 1 - in - 10 annual mean concentration of 32.8 ppb (for chronic), which are reflected in this assessment. Both the acute and chronic dietary assessments assumed that tolerance level residues o f triticonazole were found in all commodities and that all commodities consumed were 100% crop treated ( 1 00% CT). The dietary exposures for food and drinking water are well below the level of concern (LOC) for all populations for acute and chronic risk. Combined acute dietary exposure from food and drinking water is <1% of the acute population adjusted dose (aPAD) for the most highly exposed population subgroup, females 13 - 49 years old. For the general U.S. population and for all infants <1 ye ar old, the exposure is also <1% of the aPAD. The chronic dietary

exposure is estimated to be <1% of the chronic adjusted population dose (cPAD) for the general U.S. population and 1.4% of the cPAD for all infants (<1 year old), the population subgroup with the high est estimated chronic dietary exposure to triticonazole. The assessment is conservative and actual exposure is likely to be much lower. Residential Exposure/Risk Based on the proposed label restrictions , non - occupational (residential) handler exposure is not expected. However , exposure is possible during postapplication activities on treated turf (existing use) and such risks have been previousl y assessed ( S. Winfield, DP#316612, 12/20/2006). This document only presents the assessment of the proposed ne w agricultural uses of triticonazole . No residential uses are being requested at this time; therefore, no residential risk assessment has been conducted . Aggregate Risk Acute and chronic aggregate assessments consider dietary (food + drinking water) exp osure only and are therefore, addressed in the dietary risk assessments (dietary risk estimates were not of concern). However, short - and intermediate - term aggregate assessments consider residential postapplication incidental oral exposure for children in addition to background dietary exposure. All aggregate risk assessments indicated risks were not of concern as the margins of exposure (MOEs ) ranged from 740 to 1100 and are greater than the LOC of 100 . Occupational Exposure/Risk Occupational handler exposure is expected for individuals involved in commercial seed treatment (primary

handlers) and planting treated seeds (secondary handlers). The results of the occupational handler exposure and risk assessment indicate that inhalation risks do not exceed HED’s LOC (i.e., MOEs , ranging from 2,200 to 3,200,000 , are greater than the L OC of 100 ) at the baseline level of risk mitigation (i.e., no respirator) for any of the cereal seed treatment scenarios .

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There is the potential for postapplication exposures following the planting of triticonazole treated seeds. Sustained levels of contact with treated seed after it has been placed in the soil or other planting media would not be expected because no routine cultural practice required for the production of agricultural commodities involves such an activity as defined in the no/low contact criteria in the Worker Protection Standard (WPS) . Therefore, no quantitative postapplication assessment is required for exposure to treated seeds that have already been plant ed . The triticonazole ai has been classified in Toxicity Category III for acute dermal toxicity and Toxicity Category IV for primary

eye irritation and primary skin irritation. The Worker Protection Standard (WPS) requires a 12 - hour restricted entry interval (REI) for active ingredients classified as Toxicity Category I II or IV for these routes of exposure. Environmental Justice Considerations 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 L ow - Income Populations," (http://www.eh.doe.gov/nepa/tools/guidance/Volume1/2 - 6 - EO_12898envjustice.pdf). OPP ty pic all y considers the highest potential exposures from the legal use of a pesticide when conducting human health risk assessments including, but not limited to, people who obtain drinking water from sources near agricultural areas, the variability of diets wi thin the U.S., and people who may

be exposed when harvesting crops. Should these highest exposures indicate potential risks of concern, OPP further refines the risk assessments to ensure that the risk estimates are based on the best available information. Review of Human Research This risk assessment relies in part on data from studies (PHED and Seed Treatment S tandard Operating P roce dure s , or SOPs ) in which adult human subjects were intentionally exposed to a pesticide or other chemical. These studies h ave been determined to require a revi ew of their ethical conduct, have received that review, and have been determined ethical. Label Recommendations

- The labeling should state: Seed that has been treated with this product that is then packaged or bagged for future use must contain the following labeling on the outside of the seed package or bag: "Treated Seed - Do Not Use f or Food, Feed, or Oil Purposes. When opening this bag or loading/pouring the treated seed, wear long sleeved shirt, long pants, shoes, socks, and chemical resistant gloves. After the seeds have been planted, do not enter or allow worker entry i nto treated areas during the restricted - entry i nterval (REI) of 12 hours. Exception: Once the seeds are planted in soil or other planting media, the Worker Protection Standard allows workers to enter the treated area without restriction if there will be no worker contact with the treated seeds in the soil or planting media."

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- For directions for u se: The label for Triticonazole HL Fungicide must be amended to include the following rotational crop restrictions: a 120 - day plantback interval for leafy vegetables, a 365 - day plantback interval for root and tuber vegetables, and a prohibition of the planting of all other crops not listed on the label. Tol erance Recommendations

- For t olerances for the cereal grain crop group 15, except rice : A revised Section F must be submitted to reflect the tolerance recommendation of 0.01 ppm for grain, cereal, group 15 (except rice); to reflect the tolerance recommendat ion of 0.25 ppm for grain, cereal, forage, fodder, and straw, group 16 (except rice); and to reflect the correct commodity definitions. Conditions of Registration

- HED recommends conversion of conditional registration to unconditional registration for the cereal grains (except rice) upon adequate resolution of data pertaining to storage stability, field accumulation in rotational crops , and immunotox icity . Deficiencies

- 860.1380 Storage Stability : To support the reported results for 1,2,4 - triazole and the triazole conjugates, the final report of the ongoing storage stability study with free triazole and triazole conjugates in plant commodities must be submitted.

- 860.1900 Field Accumulation in Rotational Crops : Data from limited field accumulation studies on rotational crops are required.

- Biliary

Excretion Study .

- Immunotoxicity

Study . 2.0 SUMMARY OF PROPOSED USES A summary

of the proposed use directions is presented in Table 2 .0 . Information pertaining to the proposed use pattern was obtained from a 2008 sp ecimen label submitted for Triticonazole HLFungicide Seed Treatment (4.17 lb/gal FS). The EP is proposed for the control of various seed - borne diseases in cereal crops , excluding rice. Table 2 .0 shows that Triticonazole HLFungicide Seed Treatment is proposed for seed treatment on cereal grains (except rice) at a maximum rate of 0.05 lb ai/100 lb seed. The EP , Charter® Fungicide Treatment (EPA Reg. No. 7969 - 386; accepted 6/27/2007) , is currently registered on barley and wheat for preplant seed treatment at a maximum rate of 0.005 lb ai/100 lb seed. Table 2 . 0. Summ ary of Proposed Seed Treatment Use of Triticonazole. Application Ty pe Form

ulation [EPA Reg. No.] Seed Treatment

Application Rate fl ozs/100 lbs seed (lb s ai/100 lb s seed) Maximum Seeding Rate 1 (lb seed planted/A) Maximum Equivalent

Field Application Rate 2 (lb ai/A) Barley Seed Treatment 4.17 lb/gal FS

[7969 - EIT] 0.155 - 1.55

(0.005 - 0.050) 96 0.048

### 10 of 39 Field Corn and Popcorn (includes seed production) Seed Treatment 4.17 lb/gal FS

[7969 - EIT] 0.155 - 1.55

(0.005 - 0.050) 15 0.008

Sweet Corn Seed Treatment 4.17 lb/gal FS

[7969 - EIT] 0.31 ( 0.010 ) 15 0.002

Oats Seed Treatment 4.17 lb/gal FS

[7969 - EIT] 0.155 - 1.55

(0.005 - 0.050) 128 0.064

Rye Seed Treatment 4.17 lb/gal FS

[7969 - EIT] 0.155 - 1.55

(0.005 - 0.050) 112 0.056

Sorghum Seed Treatment 4.17 lb/gal FS

[7969 - EIT] 0.31 - 0.62

( 0.010 - 0.020 ) 10 0.002 Wheat and Triticale Seed Treatment 4.17 lb/gal FS

[7969 - EIT] 0.155 - 1.55

(0.005 - 0.050) 150 0.075 General Use Directions and Limitations : To be a pplied as a water -based mixture using standard or mist - ty pe seed treatment application equipment. A colorant must be added to identify the treated seed. The proposed label does not include water amounts needed to provide the mixture or slurry rate for op timum coverage, but recommends consulting a seed - treatment specialist. The product may be tank- mixed with other water -based seed treatments. Use of treated seed for food, feed, or oil processing is prohibited. Planting of any crop not listed on the labe l within 30 days after planting treated seed is not allowed. 1 From Science Advisory Council for Exposure, St andard Operating Procedure, SOP # 15, 3/2/04. 2 Calculated by the study reviewer using the maximum seed treatment rate and maximum seeding rate. 

### 3 .0 HAZARD CHARACTERIZATION/ASSESSMENT References:

- Triticonazole

– Report of the Hazard Identification Assessment Review Committee. A . Assaad , TXR# 014698, 1 0 /1 1 /2001 .

- Triticonazole

– Report of the FQPA Safety Factor Committee . C. Christensen , TXR#00508 01, 06/13/2002 .

- Triticonazole: Report of the Cancer Assessment Review Committee. J. Kidwell, TXR#0054249, 06/15/2006.

- Response to Bayer CropScience Request to Waive the Requirement of a 28 - day Inhalation Toxicity Study for Triticonazole. A. Assaad, TXR#0054207, 0 4/12/2006.

- Triticonazole (PC Code 125620) Developmental Neurotoxicity Study Waiver Request. S. Dapson, TXR#0053 4 24, 11/13/2006 .



### - Triticonazole: HED Human Health Risk Assessment for Proposed Use on Turf. PC Code: 125620, Reg Nos. 264 - ANR, 432 - REAI. S. Winfield, DP#s316612 and 313844, 12/20/2006. 

### With the exception of a new data requirement for immunotoxicity, the hazard characterization, toxicological effects, mode of action, dose response considerations , and absorption, distribution,

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metaboli sm, excretion (ADME) determinations have not changed since completion of the previous risk assessment (S. Winfield, DP#316612, 12/20/2006). A biliary exc retion study

in the rat has been submitted (MRID # 47158901 ) and is currentl y under review. The results of this study are not expected to change the hazard assessment or endpoints selected for risk assessment. Refer to the listed references f or further extensive details. Refer to Appendix A for the toxicity profile of triticonazole . Since no new toxicity data are associated with this action, the hazard characterization and endpoint selection for triticonazole summarized below are supported b y the data evaluations and conclusions from the previous risk assessment which apply directl y to this section. 3.1 Database Summary 3.1.1 Su fficiency of studies/data With the exception of an immunotoxicity study , the toxicology

database for triticonazole is complete . There are acceptable studies available for endpoint selection that include: 1) subchronic oral toxic ity

studies in rats; 2) chronic oral toxicity studies in rats and dogs, and carcinogenicity

studies in rats and mice; 3) developmental studies in rats and rabbits and a reproduction study in rats; 4) acute and subchronic neurotoxicity studies in rats; and 5 ) subchronic dermal toxicity and dermal penetration studies in rats. There is also a complete mutagenicity

battery , and a set of metabolism studies in rats. A waiver for a developmental neurotoxicity (DNT) study has been granted . 3.1 .2 Mo de of action, metabolism, toxicokinetic data Triticonazole is in the class of fungicides known as azoles which commonly inhibit the sy nthesis of ergosterol (specifically C - 14 demethylation). The data show that at higher dose levels the absorption mechanism can become saturated. The extent of absorption following oral dosing was not determined. It was not widely distributed in rat tissue. Excretion was rapid, >90% with in 4 8 hours following a single dose. It was excreted mostly from the GI tract in bile and feces , and also from the kidney . The major metabolites identified were diastereo isomers (acid metabolites) and hydrox ylated derivatives. 3.1.3 Toxicological Effects Toxicity Summary Triticonazole has low acute toxicity, is not a skin, eye, or respiratory irritant, and does not cause dermal sensitization in guinea pigs. Dermal absorption was reported to be less than 2%. Repeated dosing studies show that the liver (rat, mouse, dog) and adrenals (rat, dog, rabbit) are target organs across species. Adverse body we ight changes (rat, dog, rabbit, mouse) and neurotoxic signs (rat, dog, mouse) also were observed in multiple species. The data does not demonstrate susceptibility in the offspring. In the developmental and reproductive toxicity

studies, adverse effects on the offspring (supernumery ribs and cranial

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variations) occurred onl y at dose levels where maternal and parental toxicities were seen. In addition, t oxicity

in the offspring was m ore severe compared with adults (in rabbits, an increase in mortality

wa s obser

ved in both dams and offspring at the same dose ). Triticonazole was negative for mutagenicity , and the cancer classification is “Not Likely to Be Carcinogenic to Humans” based on a lack of evidence of carcinogenicity i n rats and mice up to the limi t dose at 24 and 18 months, respectivel y . Immunotoxicity In the oral subchronic rat study (MRID 44802102) triticonazole was offered in feed for 13 weeks to 10 CD rats/sex at dose levels of 0, 25, 250, 12,500 or 25,000 ppm (males: 0, 2.0, 19.8, 1117.0, or 2309.3 mg/kg body weight/day; females: 0, 2.2, 22.3, 1183.5, or 2368.8 mg/kg/day). In addition to adverse effects on body weight and food consumption, primary target organ effects involved the thy

mus (decreased weight), adrenals (decreased weight, and in creased lesions), liver (hy pertrophy), blood (decreases in hematocrit, hemoglobin, and red blood cells) and skin (hair loss). The decrease in thy

mus weights was reported at the high dose level (2309.3 m g/kg/day). The NOAEL for th ymus weight changes was 1 117 mg/kg/day . The NOAEL for the study was 2 mg/kg/day

(males) and the LOAEL was 19.8 mg/kg/day , based on adverse effects on the adrenals (a statistically

significant increase in the incidence of adrenocortical fatty vacuolation). No other adverse effect s indicative or suggestive or indicative of immunotoxicity were observed in any other studies in the available database. A clear NOAEL for thymus effects has been established , and the points of departure for risk assessment are protective of the adverse thy mus weight change. Additionally , triticonazole does not belong to a class of chemicals that would be expected to be immunotoxic. It is not likel y that conducting a special 870.7800 immunotoxicity study will result in a NOAELless than 17 mg/kg/day whic h is presently

used as the cRfD POD. Therefore, there an additional uncertainty factor (UF DB 

### ) does not need to be applied at this time. 3.2 FQ PA Considerations 3. 2 .1 Adequacy of the Toxicity Database The toxicity

database for triticonazole is considere d complete except for: 1. additional information on absorption. A biliary excretion study

in the rat has been submitted (MRID 47158901) and is currently in review. The results of this study will provide the needed information on the extent of absorption of triticonazole in the rat, but are not expected to change the hazard assessment, endpoints selected for risk assessment, or Uncertainty

Factors for FQPA. 2. the current requirement for an immunotoxicity study .

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3.2 .2 Evidence of Neurotoxicity Neurotoxi city

was observed as transient signs (tremors, hy peractivity or h ypoactivity , convulsions, and ataxia) in the one - ye ar dog study at 150 mg/kg/day . However, no neurological effects were seen in rats, mice , or rabbits at dose levels that ca used death (rabbi ts) or at the limit dose (rats). Increases in motor activity were observed in a rat oral acute neurotoxicity study above the l imit d ose ( i.e., at 2000 mg/kg), but a LOAEL for neurological effects could not establish ed in the rat oral subchronic neurotoxic ity study (NOAEL = 695 mg/kg/day (M), 820 mg/kg/day

(F)). A DNT study waiver was submitted and granted ( S. Dapson , TXR# 0053 4 24 , 11/13/2006 ). Thus , there are no concerns for neurotoxicity associated with exposure to triticonazole at this time. 3.2 .3 Deve lopmental Toxicity Studies In the rat developmental study , extra ribs (unilateral and bilateral supernumerary ribs) were observed at the dose level where maternal toxicity (reduced body weight gain) was observed. The LOAEL was 1000 mg/kg/day and the NOAE L w as 200 mg/kg/day . In the rabbit developmental study , a reduction in maternal body weight and food consumption and increased mortality w as observed at the LOAELof 50 mg/kg/day (NOAEL = 25 mg/kg/day). No effects in the fetus were observed at the maternal LOAEL. At the developmental LOAEL of 75 mg/kg/day cranial variations, abortion and increased pre - and post implantation losses were observed. 3. 2 .4 Reproductive Toxicity Study The multigeneration reproduction study yi elded all NOAELs (parental, reproductive, offspring) occurring at 37.5 mg/kg/day and all LOAELS occurring at 250 mg/kg/day . The parental LOAEL is based on reduced body weights, mortality and microscopic lesions in adrenals. The reproductive LOAEL is based on decreased fertility . The offspring LOAEL is based on decreased pup survival and decreased pup body weights. 3.2 . 5 Additional Information from the Literature A literature search did not reveal information that would impact the risk assessment. 3.2 .6 FQ PA Safety Factor for Infa nts and Children EPA has determined that reliable data show the safety of infants and children would be adequatel y protected if the FQPA SF were reduced to 1X. That decision is based on the following findings:  There is a complete toxicity database for tri ticonazole, with the exception of a required immunotoxicity

study , and exposure is estimated based on data that reasonably account for potential exposures.

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 A clear NOAEL for thymus effects was established in the available database and the PODs for risk ass essment are protective of the se thy mus effects . Therefore, there is no basis for concern for immunotoxicity or for retaining the 10X FQPA factor due to concerns for immunotoxicity at this time.  There is no evidence of increased susceptibility following in utero and/or postnatal exposure in the developmental toxicity studies in rats or rabbits, and in the 2 - generation rat reproduction study .  There are no residual uncertainties concerning pre - and post - natal toxicity and there are no neurotoxicity

concerns.  The acute and chronic dietary food and drinking water exposure assessments utilize screening - level and modeled residue values which will not underestimate exposures/risks. 3. 3 Hazard Identification and Toxicity Endpoint Selection 3. 3 .1 Level of Concern for Margin of Exposure/Population Adjusted Dose Table 3.3 .1 . Summary of Levels of Concern for Risk Ass essment.



### Route Short - Term (1 - 30 Days) Intermediate - Ter m

(1 - 6 M onths) Long - Term (> 6 Months) Occupational (Worker) Exposure 

### Inhalation MOE < 100 MOE < 100 NA Residential Exposure 

### Inhalation MOE < 100 MOE < 100 NA 

### Incidental Oral MOE < 100 MOE < 1 00 NA 

### Dietary (Food and Water) exposure > 100% aPAD (acute, 1 - day

exposure) NA exposure > 100% cPAD (chronic exposure) 

### The LOCs for the inhalation and incidental oral routes (MOEs) are based on the conventional interspecies extrapolation (10X) and intr aspecies variation (10X) uncertainty factors. No additional un certainty factors are necessary . The LOCs for the dietary route are expressed as a percentage of a maximum acceptable dose (i.e., the dose which HED has concluded will result in no unreasonabl e adverse health effects). This dose is referred to as the population adjusted dose ( PAD ) . For acute and non - cancer chronic exposures, HED is concerned when estimated dietary risk exceeds 100% of the PAD. 3.3 .2 Recommendation for Aggregate Ex posure Risk Assessments As per FQPA, 1996, when there are potential residential exposures to a pesticide, aggregate risk assessment must consider exposures from three major routes : oral, dermal and inhalation exposures. No sy stemic toxicity was observed in the rat dermal toxicity study and there are no developmental or neurotoxic concerns; therefore, no hazard was identified via the dermal route that would contribute to aggregate expo sure/risk. However, the toxicity endpoints were selected for short - and intermediate - term incidental oral and inhalation routes of exposure may be aggregated due to the presence of a common toxicity endpoint (short - term: decreased body

### 15 of 39

weight gain, reduc ed food consumption, and mortality ; intermediate - term: decreased body weight gain and liver toxicity). Even though these exposures may be aggregated du e to common toxicity endpoints, residential exposure via the inhalation route is not expected to occur d ue to label restrictions . Therefore, short - and intermediate - term incidental oral exposures were aggregated with background dietary (food and drinking water) exposure and compared to the short - and intermediate - term incidental oral quantitative hazard estimates. Expected sources of exposure for acute and chronic durations are dietary alone (i.e., food and drinking water exposures are aggregated). 3.3 .3 Summary of Toxicological Doses and Endpoints for Triticonazole for Use in Human Risk Assessments Tables 3.3.3.1 and 3.3.3.2 summarize the up - to - date toxicological doses and endpoints for triticonazole for use in dietary and occupational human he alth risk assessments, respectivel y. Table 3. 3 . 3 . 1. Summary of Toxicological Doses and Endpoints for Triticonazole for Use in Dietary and Non - Occupational Human Health Risk Assessments . Exposure/ Scenario Point of

Departure Uncertainty/FQPA

Safety Factor s RfD, PAD,

Level of Concern for Risk Assessment Study and Toxicological Effects Ac ute Dietary (General Population, including Infants and Children) NOAEL=400

mg/kg/day UF A= 10x

UF H=10x FQPA SF= 1x Ac ute RfD =

4 mg/kg/day aPAD = 4 mg/kg/day Ac ute Neuroto xicity - Rat

LOAEL = 2000 mg/kg/day based on increased motor activity in both sexes. Ac ute Dietary (Females 13 - 49 years of age) NOAEL = 50

mg/kg/day UF A= 10x

UF H=10x FQPA SF= 1x Ac ute RfD =

0.5 mg/kg/day aPAD = 0.5 mg/kg/day Developmental - Rabbit

LOAEL = 75 mg/kg/day based on cranial variations, abortion, and increased pre - and post - im plantation losses assumed to occur following a single dose (developmental toxicity). Chronic Dietary (All Populations) NOAEL=

17.4 mg/kg/day UF A= 10x

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

= 0.17 mg/kg/day cPAD = 0.17 mg/kg/day Carcinogenicity - Mouse

LOAEL of ~ 200 mg/kg/day based on decreased body weight gain and liver toxicity. [LOAEL=202/209.5 mkd for males/females] Incidental Oral Short - Term

(1 - 30 days) NOAEL= 25

mg/kg/day UF A= 10x

UF H=10x FQPA SF= 1x Residential

LOC for MOE = 100 Developmental - Rabbit

LOAEL = 50 mg/kg/day based on decreased body weight gain, reduced food consumption, and mortality (maternal toxicity). Incidental Oral Intermediate

- Term (1 - 6 mo nths) NOAE L=

17.4 mg/kg/day UF A= 10x

UF H=10x FQPA SF= 1x Residential

LOC for MOE = 100 Carcinogenicity - Mouse

LOAEL of ~ 200 mg/kg/day based on decreased body weight gain and liver toxicity.

### 16 of 39

Table 3. 3 . 3 . 1. Summary of Toxicological Doses and Endpoints for Triticonazole for Use in Dietary and Non - Occupational Human Health Risk Assessments . Exposure/ Scenario Point of

Departure Uncertainty/FQPA

Safety Factor s RfD, PAD,

Level of Concern for Risk Assessment Study and Toxicological Effects Dermal Short - (1 - 30 days) , Intermediate - (1 - 6 months), and Long Term (>6 mo nths) None Dermal absorption is minimal (<2% of the total administered dose) regardless of dose, and rats treated by dermal occlusion for 6 - 7 hours/day for 23 days at doses up to 1000 mg/kg/day (Limit - Dose) did not exhibit any signs of systemic toxicity or dermal irritation, and no treatment - related histopathological effects were noted. Therefore, quantification of dermal risk was not conducted. Inhalation Short - Term (1 - 30 days) NOAEL= 25

mg/kg/day UF A= 10x

UF H=10x FQPA SF= 1x Residential

LOC for MO E = 100 Developmental - Rabbit

LOAEL = 50 mg/kg/day based on decreased body weight gain, reduced food consumption, and mortality (maternal toxicity). Inhalation Intermediate Term (1 - 6 mo nths) and Long- Term (>6 months) NOAEL=

17.4 mg/kg/day UF A= 10x

UF H=10 x FQPA SF= 1x Residential

LOC for MOE = 100 Carcinogenicity - Mouse

LOAEL of ~ 200 mg/kg/day based on decreased body weight gain and liver toxicity. Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant

tumor increases in two adequate rodent carcinogenicity studies as per the CARC report dated June 15, 2006, TXR No.: 005249. Point of Departure (POD) = A data point or an estimated point that is derived from observed dose - response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference do se. MOE = margin of exposure. LOC = level of concern.

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Table 3. 3 .3 .2. Summary of Toxicological Doses and Endpoints for Triticonazole 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 - (1 - 30 days) , Intermediate - (1 - 6 months), and Long Term (>6 mo nths) None Dermal absorption is minimal (<2% of the total administered dose) regardless of dose, and rats treated by dermal occlusion for 6 - 7 hours/day for 23 days at doses up to 1000 mg/kg/day (Limit - Dose) did not exhibit any signs of systemic toxicity or dermal irritation, and no treatment - related histopathological effects were noted. Therefore, quantification of d ermal risk was not conducted . Inhalation Short - Term (1 - 30 days) NOAEL=

25 mg/kg/day UF A= 10x

UF H=10x Occupational

LOC for MOE = 100 Developmental - Rabbit

LOAEL = 50 mg/kg/day based on decreased body weight gain, reduced food consumption, and mortality ( maternal toxicity). Inhalation Intermediate Term (1 - 6 mo nths) and Long - Term (>6 months) NOAEL=

17.4 mg/kg/day UF A= 10x

UF H=10x Occupational

LOC for MOE = 100 Carcinogenicity - Mouse

LOAEL of ~ 200 mg/kg/day based on decreased body weight gain and liver to xicity. Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant

tumor increases in two adequate rodent carcinogenicity studies as per the CARC report dated June 15, 2006, TXR No.: 00 5249. Point of Departure (POD) = A data point or an estimated point that is derived from observed dose - response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspe cies). MOE = margin of exposure. LOC = level of concern. 

### 3.4 ENDOCRINE DISRUPTION EPA is required under the Federal Food, Drug, and Cosmetic Act ( FFDCA ) , as amended b y FQPA, to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) “may have an effect in humans that is similar to an effect produced b y a naturall y occurring estrogen, or other such endocrine effects as the Administrator may designate.” Following recommendations of its En docrine Disruptor and Testing Advisory Committee (EDSTAC), EPA determined that there was a scientific basis for including, as part of the program, the androgen and thy roid hormone sy stems, in addition to the estrogen hormone sy stem. EPA also adopted EDSTA C’s recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may

help determine whether a substance may have an effect in humans, FFDCA authority

to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone s ys tems may be added to the Endocrine Disruptor Screening Program (EDSP).

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When additional appropriate screening and/or testing proto cols being considered under the Agen cy ’s EDSP have been developed, triticonazole may be subjected to further screening and/or testing to better characterize effects related to endocrine disruption. 4.0 PUBLIC HEALTH AND PESTICIDE EPIDEMIOLOGY DATA Refere nces:

- Revie w of

Triticonazole Incident Reports . M. Hawkins , DP# 325380, 9/19/2006. 

### There were no reports and/or cases related to triticonazole i n the OPP Incident Data S ys tem (IDS), Poison Control Centers data, California Department of Pesticide Regulati on data, the National Pesticide Information Center (NPI C) data, and the National Institute of Occupational Safety and Health’s Sentinel Event Notification System for Occupational Risks (NIOSH SENSOR) . Furthermore, no scientific literature was found concer ning human poisoning or other adverse effects from exposure to triticonazole. 5.0 DIETARY EXPOSURE/RISK CHARACTERIZATION References:

- Triticonazole: HED Human Health Risk Assessment for Proposed Use on Turf. S. Winfield, DP#s316612 and 313844, 12/20/20 06.

- Triticonazole Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for a Section 3 Registration Action for Seed Treatment of Cereals. A. Acierto, DP#366041, 06/10/2009.

- MARC Decision Memo. N. Dodd and A. Assaa d, TXR#0050233, 06/04/2001.

- Tier II Drinking Water Assessment for the Triticonazole Proposed Section 3 Registration for Use on Crop Group 15 (Cereal Grains, Except Rice) and Crop Group 16 (Forage Fodder and Hay of the Cereal Grains Group, Except Rice) . C . Sutton, DP#313847, 10/11/2006. 

### The exposure pathway s resulting from use of this chemical are dietary (food and drinking water), residential, and occupational. The residue chemistry data submitted in support of the proposed use and increased existing to lerances were summarized in the HED memorandum by A. Acierto ( DP# 360624 , 0 6 / 12 /20 09). The acute and chronic dietary exposure assessment was completed in a HED memorandum by

A. Acierto (DP# 366041 , 06/10/2009 ). Pesticide metabolism (in primary crops, rotational crops, and livestock), associated analy tical methodology) , and environmental degradation (metabolic profiles of major metabolites and degradates) were previously assessed in a human health risk assessment ( S. Winfield, DP#316612, 12/20/2006 ). See Ap pendix C for the chemical structure and metabolic profile. 5.1 Drinking Water Residue Profile Triticonazole and its transformation products are very persistent and moderatel y mobile in terrestrial and aquatic environments . These fate properties suggest that it has a potential to move

### 19 of 39

into surface water and shallow ground water while undergoing slow degradation. The EDWCs used in the dietary risk assessment were provided by EFED and incorporated directly into the die tary

assessment (C. Sutton, DP# 358625, 03/24/2009). The EDWCs used in the dietary

assessment were modeled using the surface water model PRZM - EXAMS. For the acute point estimate, the PRZM - EXAMS 1 - in - 10 y r annual maximum EDWC was used. For the chronic point estimate, the PRZM - EXAMS 1 - in - 10 ye ar annual mean EDWC was used. PRZM EXAM S EDWCs were used because they were higher (and therefore more protective) than the groundwater model ’s ( SCI - GROW’s ) EDWC. The modeled EDWCs are shown in Table 5.1. Table 5.1. Summ ary of Estimated Surface Water an d Groundwater Concentrations for Triticonazole . Surface Water Conc., ppb a Ground W ater Conc., ppb b Ac ute (1 - in - 10 - year annual concentration) 75.5 5.7 Chronic (non - cancer; 1 - in - 10 - year avg. annual concentration) 32.8 Chronic (cancer; 30 - year avg. annual concentration) 21.4

a From the Tier II PRZM - EXAMS - Index Reservoir model. Based on the FL turf scenario, using the application rate on the CHIPCO brand TRITON label (resubmitted 9/22/06) of 1.15 lb ai/A, applied by ground equipment 3 times with 14 - day inter application intervals. b From the SCI - GROW model assuming a maximum seasonal use rate of 1.15 lb ai/A, a Koc of 533 mL/g, and a half - life considered stable. 

### 5.2 Metabolism in Primary Crops The nature of the residue in plant commodities is con sidered adequately understood only

for the purpose of the proposed/registered seed treatment uses on cereal grain - ty pe crops. Based on the barley and wheat metabolism studies, triticonazole is metabolized primarily via hydrox yl ation of the dimethylcyclopentane moiety to form a series of dihydrox y m etabolites which subsequentl y cleave to form numerous minor polar metabolites. The residue of concern for cereal grain commodities, excluding rice commodities, for risk assessment and tolerance expression is parent only . Although hydrox yl ated metabolites were identified in the plant metabolism studies, they were not included as residues of concern because exposure to metabolites is not significant relative to parent, and exposure is very low from the seed treatm ent uses. No triazole metabolites [1,2,4 - triazole (T), triazol yl alanine (TA), or triazolylacetic acid (TAA)] were detected in barley

or wheat grain. 5. 3 Metabolism in Livestock The nature of the residue in livestock commodities is considered adequatel y understood only for the purpose of the proposed/registered seed treatment uses on cereal grain - ty pe crops, based on marginally

adequate dairy

cattle and laying hen studies with phenyl - labeled triticonazole only . HED has previously

deemed that triticonaz ole is the residue of concern in ruminants and poultry from seed treatment uses on barley and wheat. This determination may be extended to include seed treatment uses for all crop commodities in the cereal grains crop group.

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5.4 Analytical Methodology The contribution of triazole derivatives [1,2,4 - triazole, triazolylalanine, and triazolylacetic acid] from the use of triticonazole on barley and wheat to the aggregate exposure for human health risk assessment was previously considered (M. Doherty , DP# 322215, 0 2/ 0 7/20 06). The requested seed treatment uses of triticonazole do not result in increases in dietary exposure estimates for free triazole or conjugated triazoles. Therefore, the last dietary exposure analy ses for the triazole metabolites have no t changed. Plant Commodity

Methods An adequate L C/MS and LC/MS/MS method (Method 148.02) is available for the enforcement of the proposed tolerances for triticonazole in cereal grain matrices. A similar method, LC/MS/MS method (Method 562/0), was used f or data collection in the cereal grain field trial and processing studies. The method was adequate for data collection based on acceptable method verification and concurrent method recoveries. The validated LOQ was 0.01 ppm for triticonazole in/on all cereal grain crop matrices. Analy tical standards for triticonazole are currentl y available in the EPA National Pesticide Standards Repository. Livestock Commodity

Methods Livestock feeding studies, livestock tolerances, and livestock enforcement methods are not required for the purpose of this petition. Based on the recommended tolerances for triticonazole residues in livestock feedstuffs, the maximum reasonable dietary burdens (MRDB) for livestock were calculated at 0.089 ppm for beef cattle, 0.346 ppm f or dairy cattle, 0.038 ppm for poultry , and 0.042 ppm for swine. The results of the reviewed cow and poultry metabolism studies along with the low levels of residues found in the cereal grain field trials indicate that there is no reasonable expectation that quantifiable residues of triticonazole will occur in livestock commodities [40 CFR §180.6(a)(3)]. HED will re - examine this determination if additional uses on livestock feedstuffs are proposed in the future. Multiresidue Methods The data requirements for testing with multiresidue methods have been fulfilled. Based on the results of the testing, the multiresidue methods are not appropriate for determining triticonazole residues. Storage Stability

Methods Adequate data are available supporting the stability of triticonazole residues during frozen storage of samples collected from the cereal grain crop field trials and processing studies. Adequate storage stability data are also available for the triazole - related metabolites (T, TA, and TAA) to supp ort the storage conditions and durations of wheat, corn, sorghum, and rice grain samples from the field studies, and wheat flour and polished rice from the processing study . The adequacy of the additional triazole storage stability data to support the sto rage durations of cereal

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grain forages, fodders and/or straws, corn kernel plus cob with husk removed (K+CWHR), and sorghum stalks from the cereal grain field trial studies will be determined when the final results of an ongoing triazole storage stability study are submitted to the Agency . According to current Agency policy , storage stability

in the raw agricultural commodity (RAC) can be translated to the processed commodity. 5.5 Food Residue Profile Primary Crops The submitted magnitude of the residue data are adequate to support the requested seed treatment uses for cereal grain crops (except rice). There are adequate data for the representative crops of the cereal grain groups 15 and 16 to establish crop group tolerances. The number and locations o f field trials were conducted according to the OPPTS 860.1500 guidelines. The seed treatment rate (0.05 lb ai/100 lbs seed) used in the field trials reflects the proposed use of Triticonazole HL Fungicide (EPA Reg. No. 7969 - EI T ) on barley , field corn and popcorn, oats, rye, wheat, and triticale . However, the rate reflects 5X and 2.5X the proposed seed treatment rate for sweet corn and sorghum, respectively . The registered uses of triticonazole as a seed treatment on cereal grains, excluding rice, are expected to result in limited residues in the food supply . The field trial data indicate very low and/or non - detectable residues on edible portions of cereal grains, excluding rice. Residues of triticonazole were below the L OQ of 0.01 ppm in treated wheat grain, corn grain, corn K+CWHR, and sorghum grain. Low but quantifiable residues of triticonazole were observed in rice grain. The available data support a tolerance level of 0.01 ppm for cereal grains, group 15 (except rice). The value of 0.05 ppm proposed b y the petitioner is excessive, when rice is excluded. Moreover, the 0.01 ppm level harmonizes with Canada. A revised Section F must be submitted to reflect the tolerance recommendation of 0.01 ppm for cereal grains, group 15 (except rice). The i ndividual tolerances established for barley grain and wheat grain at 0.05 ppm in 40 CFR §180.583(a) should be deleted when the crop group tolerance is established. Residues of triticonazole were also nonquantifiable in treated field and sweet corn forage and stover, and sorghum forage and stover. Quantifiable residues of triticonazole were observed in treated wheat forage, hay and straw, and rice straw. Appropriate tolerance levels were determined statistically according to Guidance for Setting Pesticid e Tolerances Based on Field Trial Data SOP. The residue data for rice straw was excluded from the spreadsheet because the petitioner is not applying for use on rice. The tolerance spreadsheet calculated tolerances of 0.20 ppm for wheat forage, 0.25 ppm f or wheat hay , and 0.20 ppm for wheat straw. HED recommends a crop group tolerance of 0.25 ppm based on the highest calculated value for the representative crop (wheat hay). A revised Section F must be submitted to reflect the tolerance recommendation o f 0.25 ppm for the forage, fodder, and straw of cereal grains, group 16 (except rice). The individual tolerances established for barley

hay and straw, and wheat forage, hay and straw in 40 CFR §180.583(a) should be deleted when the crop group tolerance is established.

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Processed Food and Feed The processing data for field corn, rice, sweet sorghum, and wheat are adequate. The results indicate that residues of triticonazole were nonquantifiable (<0.01 ppm) in the cereal grain RACs (corn, rice, wheat, and sorghum) grown from seeds treated at 250 g triticonazole/100 kg seed (5X the maximum proposed seed treatment rate). Analysis of rice processed matrices showed that residues of triticonazol e may concentrate in hulls (2.8X ) but not significantly in bran (1 .1 X ); residues in polished rice were nonquantifiable. As the petitioner is not seeking to register use on rice at this time, no tolerances are required for rice processed matrices. Rotational Crops The confined rotational crop study is acceptable. The application rate used in the study reflects 1.4 X the equivalent per acre rate for cereal grain crops. The metabolism of triticonazole in rotated crops appears similar to those observed for primary crops, except that triazole - related metabolites were detec ted in the rotated crops. The data indicate that residues of triticonazole may be present at >0.01 ppm in 30 - DAT rotated lettuce (0.017 ppm), radish tops (0.049 ppm) and wheat forage (0.041 ppm), straw (0.133 ppm) and chaff (0.139 ppm); 120 - DAT rotated radish tops (0.016 ppm), and wheat forage (0.019 ppm), straw (0.150 ppm), and chaff (0.114 ppm); and 365 - DAT rotated wheat forage (0.025 ppm), straw (0.086 ppm) and chaff (0.133 ppm). Wheat hay

was not analyzed but forage and straw were analyzed, and residu es of triticonazole were found in forage and straw. The proposed label for the 4.17 lb/gal FS specifies that “planting of any crop not listed on the label within 30 day s after planting treated seed is not allowed”. The results of the submitted confined rotational crop study do not support this restriction. The data from the confined rotational crop study indicate that triticonazole residues greater than 0.01 ppm were detected at the 30 - day

PBI. To support a 30 - day plantback restriction on the label, lim ited field rotational crop data for leafy

vegetables, root and tuber vegetables, foliage of root and tuber vegetables, and a cereal grain are required. Until the requested data are provided, the label must be modified to specify a 120 - day

(4 - month) plantb ack restriction for leafy vegetables, a 365 - day

(12 - month) plantback restriction for root and tuber vegetables, and to prohibit the planting of all other crops not listed on the label. 5.6 International Residue Limits There are no established Codex or Me xican MRLs/tolerances on wheat or barley . In Canada, triticonazole is registered as a seed treatment for oats, barley , and wheat, and established with the following MRLs (expressed as parent only):

Eggs ............................................. 0.05 ppm Meat and meat b yp roducts of cattle, goats, hogs, horses, poultry , and sheep ............ 0.05 ppm Barley .......................................... 0.01 ppm

### 23 of 39 Milk ............................................ 0.01 ppm Oats ............................................. 0.01 ppm Wheat .......................................... 0.01 ppm The Canadian MRL levels at 0.01 ppm on barley , oats, and wheat harmonize with the recommended U.S. 0.0 1 ppm tolerance level. Additionally, no U.S. tolerances have been established on livestock commodities. No harmonization issues exist in connection with the proposed use on turf. See Appendix B for the Internatio nal Residue Limit Status (IRL S). 5.7 Dietary Exposure and Risk Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments were conducted using DEEM - FCID TM 

### (Version 2.03), incorporating food consumption data from USDA’s CSFII from 1994 - 1996 and 1998 . For both acute and chronic dietary exposure assessments, only

the expansion of cereal grain crop group 15 was considered because cereal grain crop group 16 co nsists of livestock feed items which do not contribute to the human diet. Acute Dietary

Exposure/Risk The acute anal ys es assumed that triticonazole residues are present in all registered and proposed food commodities at tolerance levels and that 100% of all commodities are treated. All processing factors were set to 1, based on the results of processing studies indicating that residues of triticonazole in processed commodities would not exceed the RAC tolerances. Drinking water residues were incorporate d directly into the dietary

assessment using the EDWCs for triticonazole in surface water , generated using the PRI SM/EXAMS models. For the acute assessment, the 1 - in - 10 year annual peak concentration of 75.5 ppb was used. The water residues were incorporated in the DEEM - FCID TM 

### into the food categories “water, direct, all sources” and “water, indirect, all sources.” The acute dietary

(food and drinking water) exposure assessment for females 13 - 49 years was performed separatel y, since the acute toxicological endpoint of concern was different from that identified for the general U.S. population . The most highly exposed population subgroup is females 13 - 49 years old. Combined acute dietary exposure from food and drinking water is less than 1% of the aPAD for females 13 - 49 years old . For the general U.S. population and for all infant s <1 year old, the exposure is also less than 1 % of the aPAD. The results of the acute dietary exposure anal ys es are reported in Table 5. 7 , and all exposures are below the LOC. With all included commodities from the expanded use of cereal grains (crop group 15), risk estimates have not increased. Thus, f or all registered and proposed uses, the acute dietary risk estimates do not exceed HED ’s LOC (i.e., <100% a PAD). Chronic Dietary

Exposure/Risk Th e chronic anal ys es assumed that triticonazole residues are present in all registered and proposed food commodities at tolerance levels and that 100% of all commodities are treated. All

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processing factors were set to 1, based on the results of processing s tudies indicating that residues of triticonazole in processed commodities would not exceed the raw agricultural commodity

RAC tolerances. Drinking water residues were incorporated directly into the dietary assessment using the EDWCs for triticonazole in s urface water, generated using the PRI SM/EXAMS models. For the chronic assessment, the 1 - in - 10 annual mean concentration of 32.8 ppb was used. The water residues were incorporated in the DEEM - FCID into the food categories “water, direct, all sources” and “water, indirect, all sources.” With the increased dietary exposure from the expanded use of cereal grains (crop group 15), the chronic dietary

risk estimates have not increased. Currently , for all included commodities for all registered and proposed use s, the chronic dietary risk estimates do not exceed HED ’s LOC (i.e., <100% cPAD). For the general U.S. population the exposure from food and drinking water utilized is still less than 1% of the cPAD. The most highly exposed population subgroup at 1.4% of the cPAD was all infants (<1 year old) and all other population subgroups are at less than 1% of the cPAD. The results of the chronic dietary exposure anal ys e s are also reported in Table 5. 7 , and again, all exposures are below the LOC . Table 5. 7 . Result of Acute and Chronic Dietary Exposure and Risk Estimates for Triticonazole . Population Subgroup Ac ute Dietary (95 th Percentile) Chronic Dietary Dietary Exposure (mg/kg/day) % aPAD* Dietary Exposure (mg/kg/day) % cPAD* General U.S. Population 0.004192 <1.0 0.000865 <1.0 All Infants (< 1 year old) 0.015052 <1.0 (0.38) 0.002431 1.4 Children 1 - 2 years old 0.006674 <1.0 0.001422 <1.0 Children 3 - 5 years old 0.006171 <1.0 0.001376 <1.0 Children 6 - 12 years old 0.004301 <1.0 0.000959 <1.0 Youth 13 - 19 years old 0.003414 <1.0 0.000694 <1.0 Adults 20 - 49 years old 0.003806 <1.0 0.000787 <1.0 Adults 50+ years old 0.003426 <1.0 0.000781 <1.0 Females 13 - 49 years old* 0.003813 <1.0 (0.76) 0.000777 <1.0 * The acute endpoint for females 13 - 49 years old is diff erent than the acute endpoint for all other subpopulations, which is why females 13 - 49 have a lower dietary exposure estimate than all infants, but a higher risk estimate. Note: The bolded values indicate the population with the highest risk estimate for e ach type of risk assessment 

### All dietary

(food with modeled EDWCs) risk estimates were below the LOC . The assessments can be considered highl y conservative as they assume all the subject crops are treated and bear residues at the tolerance level (compounded b y the conservative tolerance). Actual dietary exposure is likely

to be much lower.

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Cancer Dietary

Risk There is no evidence that triticonazole is carcinogenic to humans; therefore, a dietary cancer assessment is not required. 6.0 RESIDENTIAL (NON - OCCUPATIONAL) EXPOSURE/RISK CHARACTERIZATION There is potential for exposure to homeowners in residential settings during the application of existing registered products containing triticonazole, and from entering areas previousl y treated with tritico nazole, such as lawns where children might play , or golf courses and home gardens that could lead to exposures for adults. As a result, risk assessments were previously completed for both residential handler and postapplication scenarios ( S. Winfield, DP# 316612, 12/20/2006 ). The proposed uses of triticonazole on cereal grain crop groups (15 an d 16) do not add any additional residential exposures or risks. S pray drift is not expected to pose a risk to residents as seed treatment does not result in spray a pplications . Residential postapplication has also been previously

assessed and is not of concern with the currentl y proposed action. For aggregate calculations, Table 6 .0 presents the exposure and risk estimates calculated in the previous memo for children’s incidental oral postapplication scenarios (S. Winfield, DP#316612, 12/20/2006 ). Table 6 .0 . Children’s Total Exposure and Risk Estimates fromResidential Lawn s . Children’s Scenarios TTR/GR/SR0 (ug/cm2 or g) 1 PDR0 - norm

(m g/k g/day) 2 Short Term MOE 3 Int - Term

MOE 3 Total MOE 4

Short Term Intermediate Term (1) Hand - to - Mouth 0.64 0.017 1,500 1,000 1,200 800 (2) Mouthing Grass 2.6 0.0043 5,800 4,100 (3) Soil Ingestion 8.6 0.000058 430,000 300,000 1 TTR=turf transferable residue on day “0”; GR=grass residue on day “0”; SR0 =soil residue on day “0”. 2 PDR0norm=potential dose rate on day “0”. 3 MOE = NOAEL/PDR; where Short - and Intermediate - term NOAELs = 25 mg/kg/day and 17.4 mg/kg/day, respectively. 4 Total MOE = S - T or I - T NOAEL/to tal incidental oral exposure (hand - to - mouth + mouthing grass + soil ingestion = 0.021358 mg/kg/day) 

### 7.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure. The aggregate assessments in this document use a deterministic approach, in that point estimates of exposure from each source are added together; and e ach of the point estimates used are deterministic (dietary

exposure estimates use point estimates for food and drinking water residues [tolerance level and modeled values, respectivel y] and the residential SOP scenarios

### 26 of 39

also emplo y point estimates [central to high - end values considered protective]). Exposures are assumed to occur over the same time frame, and no use frequency data are considered. In sum, these aggregate risk assessments are screening - level assessments . 7.1 Acute Aggregate Risk Refer to Section 5. 7 , which discusses dietary exposure (food and drinking water). The dietary route alone is relevant for acute exposure and risk assessment. 7.2 Short- Term and Intermediate - Term Aggregate Risk Short - term aggregate expos ures are compared to the oral NOAEL of 25 mg/kg/day (based on decreased body weight gain and food consumption at the LOAEL of 50 mg/kg/day in the rabbit developmental study) to estimate the risk from short - term exposure. Intermediate - term exposures are co mpared to the NOAEL of 17.4 mg/kg/day (based on decreased body weight and liver toxicity

at the LOAELof ~ 200 mg/kg/day in the mouse carcinogenicity study) to estimate the risk from intermediate - term exposure. The LOC for non - occupational aggregate risk is expressed as an MOE = 100. Over the short - term (1 to 30 day s), both dietary and residential postapplication incidental oral exposure may

co - occur (exposures and risks are shown in Table 7.2. 1 ). The short - term aggregate MOEs do not exceed the LOC and, therefore, are not of concern. Table 7.2. 1 . Short - Term Aggregate Risk Calculations (Incidental oral exposure with background dietary exposure) . Population NOAEL

mg/kg/day LOC 1 Max

Allowable Exposure 2 mg/kg/day Average

Food & Water Exposure mg/kg/day Re sidential

Exposure 3 mg/kg/day Aggregate

Exposure (dietary and residential) mg/kg/day Aggregate

MOE (food and residential) 4 Children 1 - 2 25 100 0.25 0.0014 0.021 0.022 1100 All Infants (< 1 year old) 5 25 100 0.25 0.0024 0.021 0.023 1100 1 The LOC is b ased on standard inter - and intra - species uncertainty factors (10x and 10x, for a total of 100) . 2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC 3 Residential Exposure = Incidental Oral exposure (postapplication inhalation exposure is not expected, and there is no hazard via the dermal route). See S. Winfield, DP#316612, 12/20/2006 for source of residential exposure values. 4 Aggregate MOE = [NOAEL /  (Avg Food & Water Exposure + Residential Exposure)] 5 Highest exposed child subpopulation. Although the incidental oral exposure estimates are calculated with the activities of children 1 - 3 in mind (toddlers), the dietary exposure for the highest exposed child subpopulation is also aggregated with the incidental oral exposure estimate for comparison and characterization purposes. 

### Although less likel y over the intermediate - term (1 to 6 months), both dietary and residential postapplication incidental oral exposure may co - occur (exposures and risks are shown in Table 7.2. 2 ). The intermediate - term aggregate MOEs do not exceed the LOC and, therefore, are not of concern.

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Table 7.2. 2 . Intermediate - Term Aggregate Risk Calculations (Incidental oral exposure with background dietary exposure) Population NOAEL

mg/kg/day LOC 1 Max

Allowable Exposure 2 mg/kg/day Aver age

Food & Water Exposure mg/kg/day Residential

Exposure 3 mg/kg/day Aggregate

Exposure (dietary and residential) mg/kg/day Aggregate

MOE (food and residential) 4 Children 1 - 2 17.4 100 0.174 0.0014 0.021 0.022 780 All Infants (< 1 year old) 5 17.4 100 0. 174 0.0024 0.021 0.023 740 1 The LOC is based on standard inter - and intra - species uncertainty factors (10x and 10x, for a total of 100) 2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC 3 Residential Exposure = Incidental Oral exposure (postapplicatio n inhalation exposure is not expected, and there is no hazard via the dermal route ). See S. Winfield, DP#316612, 12/20/2006 for source of residential exposure values. 4 Aggregate MOE = [NOAEL / (Avg Food & Water Exposure + Residential Exposure)] 5 Highest exposed child subpopulation. Although the incidental oral exposure estimates are calculated with the activities of children 1 - 3 in mind (toddlers), the dietary exposure for the highest exposed child subpopulation is also aggregated with the incidental oral exposure estimate for comparison and characterization purposes. 

### 7.3 Long - Term Chronic Aggregate Risk Refer to Section 5. 7 , which discusses dietary exposure (food and drinking water). The dietary route alone is relevant for long - term/chronic exposure and risk assessment. 7.5 Cancer Aggregate Risk Triticonazole is classified as “not likely to be carcinogenic to humans” based on the absence of significant tumor increases in two adequate rodent carcinogenicity studies ( J. Kidwell, TXR#0054249, 06/15/2006 ) . Thus, no aggregate cancer risk needs to be assessed . 8.0 CUMULATIVE RISK CHARACTERIZATION/ASSESSMENT Triticonazole is a member of the triazole - containing class of pesticides. Although conazoles act similarly in plants (fungi) by

inhibiting ergostero l biosy nthesis, there is not necessarily a relationship between their pesticidal activity and their mechanism of toxicity in mammals. Structural similarities do not constitute a common mechanism of toxicity . Evidence is needed to establish that the chemi cals operate b y the same, or essentially the same, sequence of major biochemical events. In conazoles, however, a variable pattern of toxicological responses is found. Some are hepatotoxic and hepatocarcinogenic in mice; s ome i nduce thy roid tumors in rats; and s ome induce developmental, reproductive, and neurological effects in rodents. Furthermore, the conazoles produce a diverse range of biochemical events including altered cholesterol levels, stress responses, and altered DNA methylation. It is not clearl y understood whether these biochemical events are directly connected to their toxicological outcomes. Thus, there is currentl y no evidence to indicate that conazoles share common mechanisms of toxicity and EPA is not following a cumulative risk app roach based on a common mechanism of toxicity for the conazoles. For information regarding EPA’s procedures for cumulating effects from substances found to have a common mechanism of toxicity, see EPA’s website at http://www.epa.gov/pesticides/cumulative .

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Triticonazole and other triazole - containing pesticides can form the common metabolite 1,2,4 - triazole and two triazole conjugates (triazolylalanine and triazolylacetic acid). To support existing tolerances and to establish new tolerances for triazole - derivative pesticides, including triticonazole, U.S. EPA conducted a human health risk assessment for exposure to 1,2,4 - triazole, triazolylalanine, and triazolylacetic acid resulting from the use of all current and pending uses of any triazole - derived fungic ide. The risk assessment is a highly conservative, screening - level evaluation in terms of hazards associated with common metabolites (e.g., use of a maximum combination of uncertainty factors) and potential dietary and non - dietary

exposures (i.e., high en d estimates of both dietary and non - dietary

exposures). In addition, the Agency retained the additional 10X FQPA safety factor for the protection of infants and children. The assessment includes evaluations of risks for various subgroups, including those comprised of infants and children. The Agency ’s complete risk assessment is found in the propiconazole reregistration docket at http://www.regulations.gov, Docket Identification (ID) Number EPA - HQ - OPP - 2005 - 0497. 9.0 OCCUPATIONAL EXPOSURE/RISK PATHWAY Based upon the proposed use on seeds, occupational handler exposure is expected for individuals involved in commercial seed treatment and on - farm planting. Postapplication exposure to agricultural workers is possible if they perform tasks that involve the soil subsurface following planting of treated seeds. 9.1 Short-/Intermediate - Term Handler Risk Occupational handlers may experience short - and intermediate - term exposure to triticonazole while performing seed treatment activities in commercial settings. In addition, occupational secondary handlers may

experience short - and intermediate - term exposure while planting triticonazole - treated seeds. No chemical - specific handler exposure data were submitted in support of this use pattern. For assessing commercial seed treatment and seed planting activities, unit exposure data were taken from HED ExpoSAC Policy 14: SOPs for Seed Treatment. The amount of ai handled depends on the application rate (lb ai/100 lb seed) and the pounds of se ed treated in a day

(or the pounds of seed that can be planted in a day), all of which vary depending upon the seed type. Values for the amount of seed treated and planted per day were obtained from HED SOP # 15. The results are presented in Table 9.1 . Fo r all cereal seeds, potential occupational exposure scenarios from the use of triticonazole as a commercial seed treatment include: m ixing, loading, appl yi ng liquid formulations; b agging treated seed; s ewing bags; multiple activities; and p lanting treated seed (secondary handler). Ty pically for large - scale commercial seed treatments, workers onl y perform the specific individual tasks listed above; however, it is assumed that workers may also perform multiple activities throughout the day . As a result a “multiple activities” scenario (i.e., where one worker performs all seed treatment tasks such as loading/applying, sewing, bagging, cleaning, calibrating, repairing, forklift driving, etc.) will be addressed. Planting treated seed cons ists of

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the farmer purchasing bags of treated seed, placing the seed in the hopper, and appl yi ng seed to fields. This is considered a secondary handler exposure scenario. HED is currently

in the process of revising ExpoSAC SOP # 15 (Amount of Seed Treated or Planted per Day , 03/02/2004 ) in efforts to update the daily amount of seed treated in commercial seed treatment facilities. With the increasing demand for hybridized treated seeds, there have been modifications not only in the seed treatment equipment, but in the market shares of new and currentl y registered pesticide products. HED understands that d ue to high cost to produce hy brid seeds, direct seeding is done in a precise manner which requires lower volumes of seed per acre. However, this does not provide a direct correlation to the amount of seed which is treated in the commercial seed treatment facilities. The amount of seed treated per day at a commercial facility is summarized below for each crop.  Barley

– 718,000 lbs,  Field Corn and Popcorn

– 550,000 lbs,  Oats

– 718,000 lbs,  Rye – 718,000 lbs,  Sorghum Grain

– 718,000 lbs,  Sweet Corn

– 194,000 lbs,  Triticale

– 718,000 lbs, and  Wheat

– 718,000 lbs. 

### Based on SOP # 15 , the amount of seed planted per day is summarized below for each crop.  Barley

– 19,000 lbs (96 lb seed/A * 200 A/day),  Field Corn and Popcorn

– 3,000 lbs (15 lb seed/A * 200 A/day),  Oats

– 26,000 lbs (128 lb seed/A * 200 A/day),  Rye – 22,000 lbs (112 lb seed/A * 200 A/day),  Sorghum Grain

– 800 lbs (10 lb seed/A * 200 A/day) ,  Sweet C orn – 3,000 lbs (15 lb seed/A * 200 A/day),  Triticale

– 20,000 lbs (100 lb seed/A * 200 A/day), and  Wheat

– 30,000 lbs (150 lb seed/A * 200 A/day). 

### A summary

of the inhalation risks for each exposure scenario is presented below in Table 9.1 for short - term and intermediate - term inhalation exposures. The results of the short - and intermediate - term occupational handler exposure and risk assessment indicate that inhalation risks do not exceed HED’s LOC (i.e., MOEs range from 2,200 to 3,200,000 which are gre ater than the LOC of 100) at baseline level of risk mitigation (i.e., no respirator) for any of the cereal seed treatment scenarios .

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Table 9.1 . Short - and Intermediate - Term Triticonazole Handler Inhalation Exposures and Risks. Crop Exposure Scenario lbs s eed treated or planted/ daya Application

Rate b (lb ai/lb seed) B aseline

Inhal. Unit Exposure c,d (μg/lb ai) Baseline

Inhalation Dose e (mg/kg/day) Baseline Inhalation MOE f

(Target MOE = 100) Short - Term Intermediate Term Barley Loader/Applicator 718,0 00 0.00049 0.34 1.7E - 03 15,000 10,000

Sewer 718,000 0.00049 0.23 1.2E - 03 22,000 15,000 Bagger 718,000 0.00049 0.16 8.0E - 04 31,000 22,000 Multiple Activities 718,000 0.00049 1.6 8.0E - 03 3,100 2,200 Pla nter (Secondary Handler) 19,000 0.00049 3.4 4.5E - 04 55,000 38,000 Corn (field & popcorn) Loader/Applicator 550,000 0.00049 0.34 1.3E - 03 19,000 13,000

Sewer 550,000 0.00049 0.23 8.9E - 04 28,000 20,000 Bagger 550,000 0.00049 0.16 6.2E - 04 41,000 28,000 Multiple Activities 550,000 0.00049 1.6 6.2E - 03 4,100 2,800 Pla nter (Secondary Handler) 3,000 0.00049 3.4 7.1E - 05 350,000 240,000 Corn (sweet) Loader/Applicator 194,000 0.0001 0.34 9.4E - 05 270,000 180,000

Sewer 194,000 0.0001 0.23 6.4E - 05 390,000 270,000 Bagger 194,000 0.0001 0.16 4.4E - 05 560,00 0 390,000 Multiple Activities 194,000 0.0001 1.6 4.4E - 04 56,000 39,000 Pla nter (Secondary Handler) 3,000 0.0001 3.4 1.5E - 05 1,700,000 1,200,000 Oats Loader/Applicator 718,000 0.00049 0.34 1.7E - 03 15,000 10,000

Sewer 718,000 0.00049 0.23 1.2E - 03 22, 000 15,000 Bagger 718,000 0.00049 0.16 8.0E - 04 31,000 22,000 Multiple Activities 718,000 0.00049 1.6 8.0E - 03 3,100 2,200 Pla nter (Secondary Handler) 26,000 0.00049 3.4 6.2E - 04 40,000 28,000 Rye Loader/Applicator 718,000 0.00049 0.34 1.7E - 03 15,000 10,000

Sewer 718,000 0.00049 0.23 1.2E - 03 22,000 15,000 Bagger 718,000 0.00049 0.16 8.0E - 04 31,000 22,000 Multiple Activities 718,000 0.00049 1.6 8.0E - 03 3,100 2,200 Pla nter (Secondary Handler) 22,000 0.00049 3.4 5.2E - 04 48,000 33,000 Sorghum Grain Loader/Applicator 718,000 0.0002 0.34 7.0E - 04 36,000 25,000

Sewer 718,000 0.0002 0.23 4.7E - 04 53,000 37,000 Bagger 718,000 0.0002 0.16 3.3E - 04 76,000 53,000 Multiple Activities 718,000 0.0002 1.6 3.3E - 03 7,600 5,300 Pla nter (Secondary Handler) 800 0.0002 3.4 7.8E - 06 3,200,000 2,200,000 Triticale Loader/Applicator 718,000 0.00049 0.34 1.7E - 03 15,000 10,000

Sewer 718,000 0.00049 0.23 1.2E - 03 22,000 15,000 Bagger 718,000 0.00049 0.16 8.0E - 04 31,000 22,000 Multiple Activities 718,000 0.00049 1.6 8.0E - 03 3,100 2,200 Pla nter (Secondary Handler) 20,000 0.00049 3.4 4.8E - 04 53,000 37,000 Wheat Loader/Applicator 718,000 0.00049 0.34 1.7E - 03 15,000 10,000

Sewer 718,000 0.00049 0.23 1.2E - 03 22,000 15,000 Bagger 718,000 0.00049 0.16 8.0E - 04 31, 000 22,000 Multiple Activities 718,000 0.00049 1.6 8.0E - 03 3,100 2,200 Pla nter (Secondary Handler) 30,000 0.00049 3.4 7.1E - 04 35,000 24,000 a. HED default for lb seed treated per day from HED Science Advisory Council for Exposure Policy # 15. b. A pplication Rates based on proposed uses on label for Triticonazole HL Fungicide. c. Unit Exposures from HED Science Advisory Council for Exposure Policy #14. d. Baseline I

nhalation: No respirator e. I nhalation Dose (mg/kg/day) = daily unit exposure (μg/lb ai) x application rate (lb ai/lb seed) x amount treated or planted (lb seed/day) x conversion factor (1 mg/1,000 μg) x absorption factor (100 %) / body weight (70 kg adult).

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f. I nhalation MOE = NOAEL (25 mg/kg/day for short - term exposure and 17.4 mg/kg/day for intermediate - term exposure) / inhalation daily dose (mg/kg/day). Level of concern = 100. 

### 9.2 Short-/Intermediate - Term Postapplication Risk There is the potential for postapplication exposures following the planting of triticonazole treated se eds. Sustained levels of contact with treated seed after it has been placed in the soil or other planting media would not be expected because no routine cultural practice required for the production of agricultural commodities involves such an activity as defined in the no/low contact criteria in the Worker Protection Standard (WPS) . Therefore, no quantitative postapplication assessment is required for exposure to treated seeds that have already been planted . The restricted entry

interval ( REI ) is based on the acute toxicity of triticonazole technical material. The WPS allows workers to enter treated areas without restriction if there will be no worker contact with the treated seeds in the soil or planting media. Certain tasks, even though they are not routine, may involve contact with the soil subsurface (e.g. repair of certain irrigation equipment) and they

are covered b y the REI. HED recommends that the Registration Division ensure that appropriate language is placed on the product label to require t he label on treated seed to include the REI following the planting of treated seed. Triticonazole technical material which is classified as Category III for acute dermal toxicity and Toxicity Category IV for primary

eye irritation and primary skin irritation. Triticonazole is not a dermal sensitizer. Under the WPS for Agricultural Pesticides, the default REI is 12 hours for active ingredients classified as acute toxicity categories III or IV for these routes of entry . WPS allows workers to enter treated areas without restriction if there will be no contact with any thing that has been treated with the pesticide. 10.0 DATA NEEDS AND LABEL RECOMMENDATIONS 10.1 Toxicology The following deficienc ies should be made condition s of the registration of tritic onazole for use on cereal grains :

 

### A biliary excretion study . The metabolism study in the rat is classified Unacceptable/Guideline and does not satisfy the guideline requirement for a metabolism study [OPPTS 870.7485, OECD 417] because the extent of absor ption of the test material was not determined. It is upgradeable to Acceptable/Guideline if the registrant conducts a biliary excretion study

with the test compound (compound water solubility is too low for intravenous administration). The registrant has submitted this study and the study

is currentl y in review b y HED. These study results will not affect FQPA determinations.

 

### An Immunotoxicity Study [ OPPTS 870.7800, OECD 407 ] is currently required . This guideline is required to provide information on su ppression of the immune sy stem which might occur as a result of repeated exposure to triticonazole, after d osing b y either oral or parent al routes. Results are intended to be used along with data from routine toxicity testing, to provide more accurate info rmation on risk to the immune sy stem.

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10.2 Residue Chemistry 860.1200 Directions for Use

 The label for Triticonazole HL Fungicide must be amended to include the following rotational crop restrictions: a 120 - day plantback interval for leafy vegetables, a 365 - day plantback interval root and tuber vegetables, and a prohibition of the planting of all other crops not listed on the label. 860.1550 Proposed Tolerances

 A revised Section F must be submitted to reflect the tolerance recommendation of 0.01 ppm for cereal grains, group 15 (except rice); to reflect the tolerance recommendation of 0.25 ppm for grain, cereal, forage, fodder, and straw, group 16 (except rice); and to reflect the correct commodity definitions as listed in the introduction . (DATA Requi rement) HED recommends conversion of conditional registration to unconditional registration for the cereal grains (except rice) upon adequate resolution of data pertaining to storage stability and field accumulation in rotational crops. 860.1380 Storage S tability

 To support the reported results for 1,2,4 - triazole and the triazole conjugates, the final report of the ongoing storage stability study with free triazole and triazole conjugates in plant commodities must be submitted. 860.1900 Field Accumulatio n in Rotational Crops

 Data from limited field accumulation studies on rotational crops are required. 10.3 Occupational and Residential Exposure The labeling should state: Seed that has been treated with this product that is then packaged or bagged for future use must contain the following labeling on the outside of the seed package or bag: "Treated Seed - Do Not Use for Food, Feed, or Oil Purposes.” When opening this bag or loading/pouring the treated seed, wear long sleeved shirt, long pants, shoes, socks, and chemical resistant gloves. After the seeds have been planted, do not enter or allow worker entry i nto treated areas during the restricted - entry i nterval (REI) of 12 hours. Exception: Once the seeds are planted in soil or other planting media, th e Worker Protection Standard allows workers to enter the treated area without restriction if there will be no worker contact with the treated seeds in the soil or planting media."

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Appendix A: TOXICOLOGY ASSESSMENT A.1 Toxicology Data Requirements The requirements (40 CFR 158.340) for food and non food for triticonazole are in the table below . Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used. Test Technical Required Satisfied 870.1100 Acute Oral Toxicity ................................ ....................... 870.1200 Acute Dermal Toxicity ................................ .................. 870.1300 Acute Inhalation Toxicity ................................ .............. 870.2400 Primary Eye Irritation ................................ .................... 870.2500 Primary Dermal Irritation ................................ .............. 870.2600 Dermal Sensitization ................................ ...................... yes yes yes yes yes yes yes

yes yes yes yes yes 870.3100 Or al 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 To xicity (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 870.5265 Mutagenicity

—Gene Mutation ................................ ..... 870.5300 Mutagenicity

—Cytogenics ................................ ........... 870.5375 Mutagenicity

—Chromosome Aberration ..................... 870.5395 Mutagenicity

—Micronucleus ................................ ....... yes yes yes yes yes

yes yes yes 870.6100a Acute Delay ed Neurotox. (hen) ................................ ..... 870.6100b 90 - Day

Neurotoxicity (hen) ................................ ........... 870.6200a Acute Neurotox. Screening Battery (rat) ....................... 870.6200b 90 - Day

Neuro. Screening Battery (rat) .......................... 870.6300 Develop. Neuro ................................ .............................. no no yes yes no -

- yes yes

- 870.7485 General Metabolism ................................ ...................... 870 .7600 Dermal Penetration ................................ ........................ 870.78 00 Immunotoxicity ................................ ............................. yes yes yes yes

yes no Special Studies for Ocular Effects

Ac ute Oral (rat) ................................ ........................... Subchronic Oral (rat) ................................ .................. Six - mo nth Oral (dog) ................................ .................. no no no -

-

-

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A.2 Acute Toxicity Table A .2. Acute Toxicity o f Technical Grade Triticonazole. Guideline No. Study T ype MRID No. Results Toxicity Category 870.1100 Ac ute Oral Toxicity 44802028 44802029 LD 50 = > 2000 mg/kg

LD 50 = > 2000 mg/kg III 870.1200 Ac ute Dermal Toxicity 44802030 LD 50 = > 2000 mg/kg III 870. 1300 Ac ute Inhalation Toxicity 44802031 LC 50 = > 2.63 mg/L IV 870.2400 Ac ute Eye Irritation 44802032 Minimally irritating IV 870.2500 Ac ute Dermal Irritation 44802033 Not an irritant IV 870.2600 Dermal Sensitization 46817301 Not a sensitizer in the Buehler test in guinea pigs N/A 

### A.3 Toxicity Profile Table A.3 . Toxicity Profile of Triticonazole Technical. Guideline No. Study Type

(All Studies Acceptable) Results 870.3100 90 - Day

oral toxicity rodents - rat NOAEL = M: 2, F: 22.3 mg/kg/day LOAE L = M: 19.8, F: 1183.5 mg/kg/day based on M : Increases in the incidence of adrenocortical fatty vacuolation in males receiving  250 -ppm (19.8 mg/kg/day). See also 870.6200 and 870.4200 – adrenal vacuolation not seen at low doses . F : Hair loss, decrease d food efficiencies, adrenocortical fatty vacuolation, zona reticularis degeneration, centriacinar hepatocytic fatty vacuolation, and more severe anisocytosis and spherocytosis in females receiving  12,500 ppm. M and F: decreases in hematocrit, hemoglobin , and red blood cells (RBC), and decreased thymus weights, were noted at the high - dose. 870.3150 90 - Day

oral toxicity in nonrodents - dog Study not available. Refer to 870.4100b below . 870.3200 28 - Day

dermal toxicity - rat NOAEL = Dermal and syste mic: 1000 mg/kg/day (limit - dose). LOAELs > 1000 mg/kg/day. 870.3250 90 - Day

dermal toxicity Study not available. 870.3465 90 - Day

inhalation toxicity Request for a waiver granted as per memo from A. Assad dated April 12, 2006 (TXR # 0054207). 8 70.3700a Prenatal

developmental in rodents - rat Maternal NOAEL = 200 mg/kg/day LOAEL = 1000 mg/kg/day based on reduction in mean body weight gain from GD 12 - 16. Developm ental NOAEL = 200 mg/kg/day LOAEL = 1000 mg/kg/day based on increases in unilateral and bilateral supernumerary ribs.

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Table A.3 . Toxicity Profile of Triticonazole Technical. Guideline No. Study Type

(All Studies Acceptable) Results 870.3700b Prenatal

developmental in nonrodents - rabbit Materna l NOAEL = 25 mg/kg/day LOAEL = 50 mg/kg/day based on decreased body weight gain, reduced food consumption, and mortality. Developm enta l NOAEL = 50 mg/kg/day LOAEL = 75 mg/kg/day based on cranial variations, abortion, and increased pre - and post - implantation losses. 870.3800 Reproduction and

fertility effects - rat Parental/Systemic NOAEL = 37.5 mg/kg/day LOAEL = 250 mg/kg/day based on reduced body weights o f the F 0 females and the F 1 males and females, F 0 maternal mortality, and microscopic lesions in the adrenal gland of F 0 and F 1 ma les and females . Reproductive NOAEL = 37.5 mg/kg/day LOAEL = 250 mg/kg/day based on decreased fertility of the F 1 animals, reduced F 1 and F 2 pup survival, and reduced F 1 and F 2 pup body weight . 870.4100b Chronic toxicity dogs NOAEL = 25 mg/kg/day LOAEL = 150 mg/kg/day based on decreased absolute body weights of females, decreased weight gain by males and females, and treatme nt related toxicity to the eye, liver, adrenals, and transient neurological signs (tremors, hyperactivity or hypoactivity, convulsions, and ataxia) 870.43 00 Carcinogenicity

Rats NOAEL = M :  203.6, F : 38.3 mg/kg/day LOAEL = M - Not established. F : 286. 6 mg/kg/day based on decreased body weight and body weight gain, adrenal cortical and liver toxicity. No evidence of compound - induced carcinogenicity as per CARC report June 15, 2006). 870.42 00b Carcinogenicity mice NOAEL = M : 17.4; F : 20.1 mg/kg/day. LOAEL = M : 202.2, F : 209.5 mg/kg/day based on decreased body weight gain and liver toxicity. No significant increase in the incidence of neoplastic lesions. No evidence of compound - induced carcinogenicity as per CARC report June 15, 2006. 870.5265 Gene Mutation There was no evidence of induced mutant colonies over background. 870.5300 Cy

togenetics There was no consistent evidence of chromosomal aberrations induced

over background. 870.5375 Chromosome

aberration There was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any tested triticonazole dose at any harvest time. 870.5395 Micronucleus There was no evidence that unscheduled DNA synthesis, as determined by radioactive tracer proc edures [nuclear silver grain counts] was induced. 870.6200a Ac ute neurotoxicity

screening battery - rat NOAEL = 400 mg/kg/day LOAEL = 2000 mg/kg/day (limit - dose) based on increases in motor activity in both sexes.

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Table A.3 . Toxicity Profile of Triticonazole Technical. Guideline No. Study Type

(All Studies Acceptable) Results 870.6200b Subchronic

neurotoxicity screening battery - rat NOAEL = M : 695; F 820 mg/kg/day ( Highest doses tested) . LOAEL > 695mg/kg/day . 870.6300 Developmental

Neurotoxicity Request for a waiver was granted ( Triticonazole (PC Code 125620) Developmental Neurotoxicity Study Waiver Request . S. Dapson, TXR#0053424, 11/13/2006). 870.7485 Metabolism and

pharmacokinetics - rat This metabolism study in the rat is classified Unacceptable/Guideline and does not satisfy the guideline requirement for a metabolism study [OPPTS 870.7485, OECD 417] because the extent of absorption of the test material was not determined. It is upgradeable to Acceptable/Guideline if the registrant conducts a biliary excretion study or provides data that will help determine the extent of absorption. 870.7600 Dermal penetration

–

rat Dermal Absorption Factor [C 14 ]: 2 %.

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Appendix B: INTERNATIONAL RESIDUE LIMIT STATUS 

# INTERNATIONAL RESIDUE LIMIT STATUS Chemical Name: (1RS) - (E) - 5 - [4 - chlorophenyl) methylene] - 2,2 - dimethyl 1 - (1H - 1,2,4 - triazol 1ylmethyl)cyclopentanol Common Name: Triticonazole X Proposed tolerance □ Reevaluated tolerance □ Other Date: 02/2009 Codex Status (Maximum Residue Limits) U. S. Tolerances X No Codex proposal step 6 or above □ No Codex proposal step 6 or above for the crops requested Petition Number: PP#8F7420 DP# 360624 Other Identifier: Decision #399232 Residue definition (step 8/CXL): N/A Revie wer/Branch: P. Deschamp, A. Acierto/RAB3 Residue definition: triticonazole per se Crop (s) MRL (mg/kg) Crop(s) Tolerance (ppm) Grain, cereal, group 15 (except rice) 0.05 Grain, cereal, forage, fodder and straw, group 16 (except rice) 0.0 1

Limits for Canada Limits for Mexico □ No Limits □ No Limits for the crops requested X No Limits □ No Limits for the crops requested Residue definition: 5 - [(4 - chlorophenyl)methylene] - 2,2 - dimethyl - 1 - (1 H - 1,2,4 - triazol - 1 - yl methyl)cyclopentanol Residue definition: N/A Crop(s) MRL (mg/kg) C rop(s) MRL (mg/kg) Barley 0.01 Wheat 0.01 Oats 0.01 Notes/Special Instructions: S.Funk, 02/19/2009.

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Appendix C : METABOLISM ASSESSMENT Table C. Major Metabolites and Degradates Comm on Name (codes) Chemical Name Structure Matrices Triticonazole (RPA 400727) (1RS) - (E) - 5 - [(4 - chlorophenyl)methylene] - 2,2 - dimethyl - 1 - (1 H

- 1,2,4 - triazol - 1 - yl methyl)cyclopentanol (1RS) - (E) - 2 - (4 - chlorobenzylidene) - 5,5 - dimethyl 1 - (1 H - 1,2,4 - triazol - 1 - ylmethyl)cyclopentan - 1 - ol C H 3 C H 3 N N

N

Cl O H Primary crops : wheat and barley (up to 93% TRR) Rotational crops : lettuce, radish, and wheat Livestock commodities : cow liver (<10% TRR) and kidney (11% TRR), poultry liver (11% TRR), eggs (30% TRR), and peritoneal fat (<10% TRR) Rat feces : up to 74% of applied dose RPA 406341 (E ) - 2 - (4 - chlorobenzylidene) - trans 1,3 - dihydroxy - 5,5 - dimethyl - 1 - (1 H - 1,2,4 - triazol - 1 - yl methyl) - cyclopentane RPA 404766 (Z) - 2 - (4 - chlorobenzylidene) - 5,5 - dimethyl - 1 - (1 H

- 1,2,4 - triazol - 1 - yl methyl) - 1,3 - cyclopentanediol C H 3 C H 3 N N

N

Cl O H

O H Primary crops : wheat and barley (up to 12 - 25% TRR, 37% TRR total) Rotational crops : lettuce and wheat Livestock commodities : poultry eggs (<10% TRR 404766, 16% 406341) and peritoneal fat (<10% TRR 406341); and cow

liver (<10% TRR, both) and kidney (<10% TRR, bo th) Rat urine : 404766 identified at levels too low

to be detected by radio - HPLC, 406341 possibly identified Fate and effects : identified in soil photolysis, aerobic soil and anaerobic soil studies RPA 406780 2 - (4 - chlorobenzylidene) - 1,4 - dihydroxy - 5,5 - d imethyl - 1 - (1 H1,2,4 - triazol - 1 - yl methyl) - cyclopentane C H3 C H3 N N

N

Cl O H

O H Primary crops : wheat and barley (<10% TRR) Livestock commodities : eggs (<10% TRR) and cow

liver (30.8% TRR) Rat urine : identified at levels too low to be detected by radio - HPLC Fate and effects : identified in aerobic and anaerobic soil studies

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RPA 404886 (E) - 2 - (4 - chlorobenzylidene) - 5 - methyl - 5 - hydroxymethyl - 1 - (1 H1,2,4 - triazol - 1 - yl methyl) - 1 - cyclopentanol C H 3 N N

N

Cl O H O H Primary crops : wheat and barley (up to 25% TRR) Rotational crops : wheat Livestock commodities : cow liver (<10% TRR) and kidney (67.8% TRR); and poultry liver (12% TRR), eggs (16% TRR) and peritoneal fat (<10% TRR) Rat urine : identified at levels too low to be detected by radio - H PLC (and RPA 405826) Rat feces : present (and RPA 405826) Fate and effects : identified in aerobic and anaerobic (and RPA 405826) soil studies RPA 406203 z - isomer of parent (Z) - 2 - (4 - chlorobenzylidene) - 5,5 - dimethyl - 1 - (1 H

- 1,2,4 - triazol - 1 - ylmethyl)cyclopentan - 1 - ol C H 3 N N

N

O H C H 3 Cl Primary crops : barley (<10% TRR) Fate and effects : identified in aqueous photolysis and soil photolysis studies

RPA 406972 (E) - 2 - me thyl - 2 - carboxylate - 5 - (4 - chlorobenzylidene) - 1 - (1 H - 1,2,4 - triazol - 1 - ylmethyl) - 1 - cyclopentanol C H 3 N N

N

Cl O H H O O C Livestock commodities : cow liver (<10% TRR), and kidney (<10% TRR), poultry eggs (<10% TRR) and liver (19% TRR). Rat urine : diastereomers up to 25% of applied dose Rat feces : present 1,2,4 - Triazol e or free triazole 

### N N N H Not identified in wheat and/or barley grain Fate and effects: data limited, from <10% to up to 30% of the applied radiolabeled parent remained unidentified in different studies Triazole acetic acid 

### N N N H O O C Not identified in wheat and/ or barley grain Fate and effects: data limited, from <10% to up to 30% of the applied radiolabeled parent remained unidentified in different studies