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EPA REGISTRATION DI V I SIO N COMPANY NOTICE OF FILING FOR PESTICIDE PETITIC I N:S PUBLISHED IN THE FEDERAL REGISTER

EPA Registratio n Division contact : [Tony Kish , 703-308-9443] 

### INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In C il : ! i c s where the outline element does not apply, please insert 1 1 NA- Remove" and main t iliin the outlin e . Please do not change the margins ,font, or format in your pesticide petition

. Simply replace the instructions that appear in gree n , i. e . , 1 1[insert compan•• r na me] , " with the information specific to your action. 

### TEMPLATE: [Syngenta Crop Protection LLC] [Syngenta Crop Protection LLC. PP#] EP • has received a pes+icide petition PP# fro n [Syngenta Crop Protectio r LLC. , P.O. Box 18300 , Greensboro, NC 27419-8300] proposing. pursuant to section 408{d) ofthe Federa l

. .ood , Drug , anJ Cosmetic Act ( FFDCA) , 2 1 U.S.C. 346a(d), to amend 40 CFR part 180.475. 1. by hrreasing t'le establisred tolerance for residueof [Difenoconazole ::. { 2 - [2-chloro-4 - (4-chlorophenoxy)]phenyl-4- methyl - 1,3-dioxolan -2-ylmethyl] -l.H 1,2,4, -triazole) ] n or on toe raw agricultura l co m 11Hy [Fruit , pome , gr oup 11 - 10] tro n [1] lPPm) to [3] ppm an [apple , wet pomace] 'rom [4.5] (p, ' ) 

### to [7.5] ppm. EPA has determined that the petition contains data or inform tion regarding the elements set forth in section 408 (d)(2) of FDDCA; however,EPA has not fully evalu ted the sufficiency of the submitted data at this time or whether the data supports gran mg of the petition. Additional data may be needed before EPA rules on the petition. 

### A. 

### Residue Chemistry

### 2 1. Plant metabolism. The nature of the residues in plants is understood for the purpose of the pro pc sed tolerance. The metabolism of 1 4 C-difenoconazole has been studied using both p 'te nyl and triazole labels in wheat, tomatoes, potatoes, grapes, and spring rape . The metabolic pathway was the same in these four separate and distinct crops. There b re, the metabolis m of difenoconazole is considered to be adequately understood f : 1·· all crops , per EPA Test Guideline 86 0

. 1300. 2 Anal·,tical '71ethod. 

### i

. **Food** [Syngenta Crop Protectio n , Inc. has submitted ;; practical analytical method (AG-5758 , master record identification (MRID) No. 428065-04) for detecting and measuring levels of difenoconazole in or on food with t limit of quantitation (LOQ) that allows monitoring of food with residues at or above th e levels set in the proposed tolerances. EPA has validated this method and copies h a'd: ! been provided to FDA for insertion into pesticide analytical manual (PAM) II. Meth od REM 147.08 (MRID 46950222) is also available for enforcement method , for the determination of residues of difenoconazole in crops . Residues are qualified by liq u ic' chromatography (LC)/mass spectrometry (MS)/(MS) The method is available to any : t ne who is interested , and may be obtained from the Field Operations Division, Office o l Pesticide Programs. 

### ii. **Livestock.** Syngenta Crop Protection , Inc. has submitted a practica l analytical met h od (AG-544A, MRID-43292401) for detectin g and measuring levels of difenoconazole in or on cattle tissues and milk and poultry tissues and eggs , with a LOQ that allows monitoring of food with residues at or above the levels set in the proposed toleran u •s . EPA has validated this method and copies have been provided to FDA for insertion i n to PAM II. The method is available to anyone who is interested , and may be obtained ' r om the Field Operations Division , Office of Pesticide Programs. Tolerances in meat , mil k

. poultry or eggs were established for enforcement purposes.] 3 MC!gn•tude of 'esidues [Syngenta conducted adequate magnitude of resi d u t trials on Fruit, pome,group 11 - 10 under OPPTS 860.1500 to support the requested Jse of difenoconazole. These residue trials satisfy the requested tolerance on Fruit, po r · 1 !,. group 11 - 10.] B. Toxicological Profile EPA has evaluated the available toxicity data and considered its validity, complete '•:!SS, and reliability as well as the relationship of the results of the studies to human risk EPA has also considered available information concerning the variability of the sensiti• ties of major identifiable subgroups of consumers, including infants and children. Sp r.ific

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information on the studies received and the nature of the toxic effects cause by difenoconazole as well as the n o- observed -adverse-effect- level (NOAEL} from the toxicity stu ...1: -- ... '"'c at the following we .ite: http: / /edocket.access.gpo.gov/2010/2010-9759.htm . A summary of the toxicolc ,ical endpoints for l.:

.................... - e . .:;eu iO• m... . a .. , - ,sk assessment is discussed in Unit III.A and B. of the final rule published in the Federal Registe r of April 28, 2009 (75 FR 

## r: ges 22256-22263} (FRL-8817-3}. 1

. Acute toxicity. [Insert text.]

2

. Genotoxicty. [Insert text.]

3. Reproductive and developmental toxicity. [Insert text.]

4

. Subchronic toxicity. [Insert text.]

5

. Chronic toxicity [Insert text.]

6. Animal metabolism

. [Insert text.]

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. Metabolite toxicology [Insert text.]

8. Endocrine disruption . [Insert text.]

C. Aggregate Exposure 1. Dietary exposure [Tier Il l acute , short-term and chronic dietary exposure evaluations were performed for difenoconazole , 1 - [2- [2-chloro-4- (4- 

### ch lorophenoxy)phenyl] -4- methyl- 1,3-dioxolan -2-ylmethyl] - 1H - 1,2,4-triazole , using 

### t e Dietary Exposure Evaluation Model (DEEM- FCIDTM Version 3.16} from Exponent and

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consumption data from the USDA NHANES 'W hat We Eat in America" survey, 2003- 2008. These difenoconazole exposure assessments included all current and pendin · (rapeseed, Crop Group 20) uses plus proposed new post- harvest uses on pome fruit (Crop Group 11 - 10) and foliar application on dried legumes (Crop Group 

### GC). These assessments utilized residue data from field trials where difenoconazole was applie: at the maximum intended use rate and samples were harvested at the minimum preharvest interval ( PHI) to obtain maximum residues. Empirically derived processing factors were used in these assessments when available ; all other processing factors

_sed the DEEM - FCID TM Version 7.87 defaults. Secondary residues in beef liver and kidne• 1 were estimated based on "maximum reasonably balanced diets" and transfer information from feeding studies. Percent crop treated (%CT) values were estimate:! based upon economic, pest, and competitive pressures. Drinking water estimates v• . •re selected using the higher of the estimated drinking water concentrations (EDWCs) fn · surface and ground wate r. 

### i. Food [Acute exposure. Acute (food only) risk assessments for difenoconazole we · e performed for all population subgroups using an acute reference dose (aRfD) of 0.25 mg/kg - bw/day, based upon a neurotoxicity study in rats with a no observed adverse effect level (NOAEL) of 25 mg/kg - bw/day and an uncertainty factor (UF) of 100X. The 

### lOOX safety factor includes intra- and inter-species variations ; no additioP 

### =1 1 FQPA safety factor was applied. For the purpose of the aggregate risk assessment, 

### ·:t, e exposure value was expressed in terms of margin of exposure (MOE), which was calculated by dividing the NOAEL by the exposure for each population subgroup. In addition, exposure was expressed as a percent ofthe acute reference dose (%aRfD). At the 99.9th percentile , acute (food only) exposure to the U.S. population resulted in cl MOE of 702 (14.2% of the aRfD of 0.25 mg/kg - bw/day). The most exposed subpopulation was children (1 -2 years old) with a MOE of 344 (29.0% of the aRfD of 0.2.3 mg/kg - bw/day). Since the Benchmark MOE for this assessment was 100 and since 

### t ' e EPA generally has no concern for exposures above the Benchmark MOE or below 1 0 0% of the reference dose , Syngenta believes that there is a reasonable certainty that no harm will result from acute dietary (food) exposure to residues arising from all curn n t, pending, and proposed uses for difenoconazole]. Chronic Exposure. Chronic (food only) risk assessment for difenoconazole were performed for all population subgroups using a chronic reference dose (cRfD) of 0.0 1 mg/kg - bw/day, based on a combined chronic toxicity/carcinogenicity study in r ts with a no observed adverse effect level (NOAH) of 0.96 mg/kg - bw/day and an uncertainly factor of 

### lOOX. The 

### lOOX safety factor includes intra- and inter-species variations; no additional FQPA safety factor was applied. For the purpose of the

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aggregate risk assessment, th e exposure values were expressed in terms of margin col exposure ( MOE ) , which was calculated by dividing the NOAEL by the exposure for e n ; h population subgroup. In addition , exposure was expressed as a percent of the chror ic reference dose ( %cRfD )

. Chronic (food only) exposures to the U

. S. population resu i 1"E!cl in a MOE of 1,20 1 (8.0% of the cRfD of 0.0 1 mg/kg - bw/day). The most exposed sub· population was children (1 -2 years old) with a MOE of 366 {26.2% of the cRfD of 0. 0 1 mg/kg - bw/day). Since the Benchmark MOE for this assessment was 100 and since t h e EPA generally has no concern for exposures above the Benchmark MOE or below 1 0C% of the reference dose , Syngenta believes that there is a reasonable certainty that no harm will result from chronic dietary (food) exposure to residues arising from all curren t , pendin g , and proposed uses for difenoconazole. **Cancer.** A cancer dietary assessment was not conducted

. Difenoconazole is classifi ( d as a Group C , "possible human carcinogen," with a non - linear (MOE) approach for human risk characterization (CPRC Document, 7/27/94 , Memo , P. V. Shah, March 3, 2007, HED Doc. No. 0054532)

. 

### ii. **Drinking water.**  [The Estimated Drinking Water Concentrations (EDWCs) of difenoconazo

, le (CGA169374) determined as tota l toxic residues of difenoconazole 21 

### 1d its degradate (CGA205375) were determined using Tier I models SCI -GROW (Screen 

### 1 g Concentration in Ground Water) to estimate pesticide concentrations in ground wa' : f't and Tier II model PRZM/EXAMS (Pesticide Root Zone Model/Exposure Analysis Mode ing System) to estimate pesticide concentration in surface water. All registered and proposed uses on pome fruit and legumes were assessed. Based on the PRZM/EXM /I S modeling , the currently registered grape use provided a surface water acute EDWC of 20.0 parts per billion (ppb) and a surface water chronic EDWC of 13.5 ppb. Based o · the SCI -GROW modeling , the currently registered golf course turf use provided a ground water acute and chronic EDWC of 0.0136 ppb. Since the surface water EDWCs excetd the ground water EDWC , the surface water values were used for risk assessment purposes and will be considered protective for any ground water exposure concern:. **Acute Exposur** 

**e from**  **Drinking Water:**  The acute surface water EDWC of 20.0 ppb \ II ' .as input directly into the DEEM - FCIDT"' software as "water, direct and indirect , all sources" to model the acute drinking water exposures. Exposure contributions at the 99.9th percentile of exposures were determined by taking the difference between the aggregate (food +drinking water) exposures and the food (alone) exposures for eac b population subgroup. Acute drinking water exposure U.S

. population resulted in a l vl OE of 28 , 902 {0.3% ofthe aRfD of 0.25 mg/kg - bw/day). The most exposed sub- populat : o n was children ( 1 - 2 years old) with a MOE of 18,81 1 (0.5% of the aRfD of 0.25

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mg/kg/day)

. Since the Benchmark MOE for this assessment was 100 and since EPA generally has no concern for exposures above the Benchmark MOE or below 100% o .; the aRfD, Syngenta believes that there is a reasonable certainty that no harm will re ! itJ It from acute drinking water exposure to residues arising from the registered , pending 11nd proposed uses for difenoconazol e . 

### Chronic **Exposure from**  **Drinking Water.**  The chronic surface water EDWC ·)f 13.5 ppb was input directly into the DEEM - FCID sof tware as "wate r, direct a nt 1 indirect, all sources" to m odel the chronic drinking water exposures. Chronic drinking water exposure to the U. S

. population resulted in a MOE of 3,396 (2 b % of the cRfD of 0

.01 mg/kg - bw /day)

. Chronic drinking water exposure to the most exposed sub- population (all infants, <1 year old) resulted in a MOE of 1,317 (7.3% of the cRfD of 0

.01 mg/kg - bw /day)

. Since the Benchm ark MOE for thiH assessm ent was 100 and since EPA generally has no concern for exposures above the Benchm ark MOE or below 100% of the cRfD, Syngenta believes tl ' 1 t 

### there is a reasonable certainty that no harm will result from chronic drinking W<tter exposure to residues arising from all registered , pending and proposed uses 

### r or d ifenoconazole.] 2. Non Dieta

-

y Exposure The use of difenoconazole on ornamentals and flov

.' 'l' gardens ( Inspire® , Ready-to- Use spray) and golf courses (Quadris ToprM, Heritage To p·· " , BriskwayTM) may result in residentia l handler or post-application exposures to selecte :1 subgroups. A short-term toxicological dermal and inhalation endpoint of 1.25 mg/k g bw/day was selected based upon the no observed adverse effect level (NOAEL) fro n · a 2-generation reproductive study in rats with an uncertainty factor of 

### lOOX, which includes intra- and inter-species variations; no additional FQPA safety factor was applied. Exposure values were expressed in terms of margin of exposure (MOE), whi· :' was calculated by dividing the NOAEL by the exposure for each subgroup. Adult gardeners 19+ years old had a short-term residentia l MOE of 249 and youth garde nr:. 1 s had a short-term residentia l MOE of 363; there were no other exposed subgroups. Since the Benchmark MOE for this assessment was 100 and since the EPA generally h as no concern for exposures above the Benchmark MO E , Syngenta believes that there i, a reasonable certainty that no harm will result from short-term residential exposure to residues arising from all current, pending , and proposed uses for difenoconazole.



### D. Cumulative Effects

### 7 

### [Cumulative Exposure to Substances with a Common Mechanism of Toxicity. Section 408(b)(2)(D)(v) requires that, when considering whether 

### to establish , modif t, or revoke a tolerance , the Agency consider "available information" concerning the cumulative effects of a particular pesticide's residues and "other substances that h ave a common mechanism of toxicity". An ongoing series of studies being conducted by t hE! U.S. Triazole Task Force (USTIF) are designed to provide the Agency with more complete toxicological and residue information for 1,2,4 triazole and two conjugate :•. .. triazolylalanine and triazolyl acetic acid, metabolites common to most of the triazole fungicides. Upon completion of review of those data,EPA will prepare a more sophisticated assessment based on the revised toxicological and exposure database·:; For the purposes of this tolerance action , the EPA has not assumed that difenocona ; • , )le has a common mechanism of toxicity with other substances.] E. 

### Safety Determination

1 

### US roo " 1

a 

### i n. [The acute dietary exposure analysis (food plus water) showed that exposure from all current, pending and proposed uses of difenoconazo ' :! would result in a MOE of 685 (14.6 % of the aRfD of 0.25 mg/kg - bw/day) for the ge n1:-ral U.S

. population, which exceeds the Benchmark MOE of 100. For the short-term aggregate exposure analysis the corresponding food, water and residentia l MOEs w1:. re aggregated using the inverse MOE approach. The short-term aggregate (food , drinl:ing water, and residential) MOE was 205 for the general U.S

. population , which exceed.: ·t he Benchmark MOE of 100. The chronic dietary exposure analysis (food plus water) showed that exposure from all current, pending , and proposed uses of difenoconazo e resulted in a MOE of 887 (10.8% of the cRfD of 0.0 1 mg/kg - bw/day) for the general 

### J .S. population , which also exceeds the Benchmark MOE of 100. Based on the complet 1: 1 1ess and reliability of the toxicity data supporting these petitions , Syngenta believes th a · : there is a reasonable certainty that no harm will result from aggregate exposure to residues arising from all current, pending , and proposed uses of difenoconazole, including anticipated dietary exposure from food , water, and all other types of non·· occupationa l exposures.] 2 

### 'nfonts and children [The acute dietary exposure analysis (food plus wate r: showed that exposure from all current, pending and proposed uses of difenoconazol:? would result in a MOE of 338 (29.5% of the aRfD of 0.25 mg/kg - bw/day) for the mo :1 sensitive population subgroup , children 1 -2 years old , which exceeds the Benchma rk MOE of 100. For the short-term aggregate exposure analysis the corresponding fooc , water and residentia l MOEs were aggregated using the inverse MOE approach

. ThE! short-term aggregate (food, drinking water, and residential) MOE was 413 for child "( n

### 8



### (1

-2 years) , which exceeds the Benchmark MOE of 

### 100. The chronic dietary exposu analysis (food plus water) showed that exposure from all current , pending , and proposed uses of difenoconazole resulted in a MOE of 

### 317 (30.3% of the cRfD of 

### 0.0 1. mg/kg - bw/day) for the most sensitive population subgroup, children 

### 1 -2 years old, which exceeds the Benchmark MOE of 

### 100. Based on the completeness and reliabili :y of the toxicity data supporting these petitions , Syngenta believes that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to residues arising from all current , pending , and proposed uses of difenoconazole , including anticipated dietary exposure from food, water, and all ot · r types of non -occupational exposures.] F

. International Tolerances [Codex Alimentarius Commission established Maximum Residue Limits ( MRI

.-) for difenoconazole in various agricultura l commodities including asparagus , banan a , beans , except broad bean and soya bean, broccoli , Brussels sprouts, cabbages , heac

. carrot, cauliflower, celeriac, celery, cherries , edible offal {m ammalian ) , eggs, garlic, ginseng , grapes , leek, lettuce , head , lettuce, leaf, mango, meat, milks , nectarine, olilt•: !s , papaya , passion fruit, peach , peas (pods and succulent/immature seeds) , plums (including prunes) , pome fruits , potato, poultry meat , poultry , edible offal of, rape ! ;.- ed, soya bean (dry), sugar beet, sunflower seed , tomato , tree nuts , wheat, and wheat sl aw and fodder (dry)

.]