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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS 

PUBLISHED IN THE FEDERAL REGISTER

EPA RegistrationDivision contact:[Tony Kish,703-308-9443]

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In cases 

where the outline element does not apply,please insert 11NA-Remove" and maintain 

the outline.Please do not change the margins,font,or format inyour pesticide

petition.Simply replace the instructions that appear ingreen,i.e.,

11

[insert

company name]," withthe informationspecific to your action.

TEMPLATE:

[Syngenta Crop Protection LLC),PP# 4F8231]

EPA has received a pesticide petition PP# 4F8231from [Syngenta Crop 

Protection LLC., P.O. Box 18300, Greensboro,NC 27419-8300] proposing, pursuant to 

section 408(d) of the FederalFood,Drug,and Cosmetic Act (FFDCA), 21U.S.C. 346a(d), 

to amend 40 CFR part 180.475.

1 by estab'ishing tolerance for res·dues of [Difenoconazole :1[2-[2-chloro-4-

(4-chlorophenoxy)]phenyl-4-methyl-1,3-dioxolan-2-ylmethyi]-1H-1,2,4,- 

triazole) ] in or on the raw agriculturalcommodity [Pea and bean, dried 

shelled, except soybean,subgroup 6C] at [0.2] (ppm); [pea,vine] at [10]

(ppm ;[pea,hay] at [40] (ppm); [Bushberry, subgroup 13-07B) at [3.0] (ppm).

2. By removingtolerance for chickpeas at [0.08] (ppm).

EPA has determined that the petition contains data or information regarding the 

elements set forth in section 408 (d)(2) of FDDCA;however,EPA has not fully evaluated 

the sufficiency of the submitted data at this time or whether the data supports granting 

of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The nature of the residues in plants is understood for the 

purpose of the proposed tolerance. The metabolism of 14C-difenoconazole has been 

studied using both phenyl and triazole labels in wheat,tomatoes,potatoes,grapes,and 

spring rape. The metabolic pathway was the same in these four separate and distinct
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crops. Therefore,the metabolism of difenoconazole is considered to be adequately 

understood for all crops,per EPA Test Guideline 860.1300.

2.Analytical method. Syngenta Crop Protection,Inc. has submitted a practical 

analytical method (AG-5758, master record identification (MRID) No. 428065-04) for 

detecting and measuring levels of difenoconazole in or on food with a limit of 

quantitation (LOQ) that allows monitoring of food with residues at or above the levels 

set in the proposed tolerances. EPA has validated this method and copies have been 

provided to FDA for insertion into pesticide analytical manual (PAM) II. Method REM

147.08 {MRID 46950222) is also available for enforcement method,for the 

determination of residues of difenoconazole in crops. Residues are qualified by liquid 

chromatography (LC)/mass spectrometry (MS)/(MS) The method is available to anyone 

who is interested,and may be obtained from the Field Operations Division,Office of 

Pesticide Programs.

ii. Livestock. Syngenta Crop Protection,Inc.has submitted a practical analytical method 

(AG-544A,MRID-43292401) for detecting and measuring levels of difenoconazole in or 

on cattle tissues and milk and poultry tissues and eggs, with a LOQthat allows 

monitoring of food with residues at or above the levels set in the proposed tolerances. 

EPA has validated this method and copies have been provided to FDA for insertion into 

PAM II. The method is available to anyone who is interested,and may be obtained from 

the Field Operations Division,Office of Pesticide Programs. Tolerances in meat,milk, 

poultry or eggs were established for enforcement purposes.]

3. Magnitude of residues. Syngenta conducted adequate magnitude of residue 

trials under OPPTS 860.1500 to support the requested uses of difenoconazole. These 

residue trials satisfy the requested tolerance on legumes,subgroup 6C and bushberry 

subgroup 13-078.

B. Toxicological Profile

EPA has evaluated the available toxicity data and considered its validity, completeness, 

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 sensitivities 

of major identifiable subgroups of consumers, including infants and children. Specific 

information on the studies received and the nature of the toxic effects caused by 

difenoconazole as well as the no-observed-adverse-effect-level (NOAEL) from the 

toxicity studies can be found at the following website: 

http://edocket.access.gpo.gov/2010/2010-9759.htm A summary of the toxicological 

endpoints for difenoconazole used for human risk assessment is discussed in Umt III.A 

and B. of the final rule published in the Federal Register of April 28, 2009 (75 FR pages

22256-22263) (FRL-8817-3}.

1. Acute toxicity [Insert text.]
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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.]

7. Metabolite toxicology. [Insert text.]

8.Endocrine disruption.[Insert text.]

C. Aggregate Exposure

1.Dietary exposure. Tier Illacute, short-term and chronic dietary exposure evaluations 

were performed for difenoconazole,1-[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-

dioxolan-2-ylmethyi]-1H-1,2,4-triazole,using the Dietary Exposure Evaluation Model(DEEMFCIDTM Version 3.16) from Exponent and consumption data from the USDA NHANES "What We 

Eat in America" survey, 2003-2008. These difenoconazole exposure assessments included all 

current and pending (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 6C), 

artichoke,ginseng, greenhouse cucumbers,and blueberries (Crop Groups 13-07B). These 

assessments utilized residue data from field trials where difenoconazole was applied at the 

maximum intended use rate and samples were harvested at the minimum pre-harvest interval 

(PHI) to obtain maximum residues. Empirically derived used the DEEM-FCIDTMVersion 7.87 

defaults. Secondary residues in beef liver and kidney were estimated based on "maximum 

reasonably balanced diets" and transfer information from feeding studies. Percent crop treated 

(%CT) values were estimated based upon economic,pest, and competitive pressures. Drinking 

water estimates were selected using the higher of the estimated drinking water concentrations 

(EDWCs) for surface and ground water.
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h

i Food. Acute exposure. Acute (food only) risk assessments for difenoconazole were 

performed for all population subgroups using an acute reference dose (aRfD) of 0.25 mg/kgbw/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 lOOX.The 100X safety factor

includes intra- and inter-species variations;no additionalFQPA safety factor was applied. For 

the purpose of the aggregate risk assessment,the 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 of the acute

reference dose {%aRfD). At the 99.9

1

percentile,acute (food only) exposure to the U.S.

population resulted in a MOE of 715 {14.0% of the aRfD of 0.25 mg/kg-bw/day). The most 

exposed sub-population was children (1-2 years old) with a MOE of 347 (28.8% of the aRfD of

0.25 mg/kg-bw/day). Since the Benchmark MOE for this assessment was 100 and since the EPA 

generally has no concern for exposures above the Benchmark MOE or below 100% 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 current,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 0.01mg/kg-bw/day,based on

a combined chronic toxicity/carcinogenicity study in rats with a no observed adverse effect level

{NOAEL) of 0.96 mg/kg-bw/day and an uncertainly factor of 100X. The 100X safety factor 

includes intra- and inter-species variations;no additional FQPA safety factor was applied. For 

the purpose of the aggregate risk assessment,the exposure values were 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 of the chronic

reference dose (%cRfD). Chronic (food only) exposures to the U.S.population resulted in a MOE

of 1,305 (7.4% of the cRfD of 0.01mg/kg-bw/day). The most exposed sub-population was 

children (1-2 years old) with a MOE of 393 {24.5% of the cRfD of 0.01mg/kg-bw/day). Since the 

Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for 

exposures above the Benchmark MOE or below 100% 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 current,pending,and proposed uses for difenoconazole.

Cancer. A cancer dietary assessment was not conducted. Difenoconazole is classified 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 difenoconazole

{CGA169374) determined as totaltoxic residues of difenoconazole and its degradate 

(CGA205375) were determined using Tier Imodels SCI-GROW {Screening Concentration in 

Ground Water) to estimate pesticide concentrations in ground water and Tier II model 

PRZM/EXAMS (Pesticide Root Zone Model/Exposure Analysis ModelingSystem) to estimate 

pesticide concentration in surface water. All registered and proposed uses on artichoke, 

ginseng,green-house cucumbers and blueberries were assessed. Based on the SCI-GROW 

modeling,the currently registered golf course turf use provided a ground water acute and
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chronic EDWC of 0.0136 ppb. Based on the PRZM/EXAMS 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. Since the surface water EDWCs exceed the ground water 

EDWC,the surface water values were used for risk assessment purposes and willbe considered 

protective for any ground water exposure concerns.

Acute Exposure from Drinking Water. The acute surface water EDWC of 20.0 ppb was input 

directly into the DEEM-FCID'M software as "water,direct and indirect,all sources" to model the 

acute drinking water exposures. Exposure contributions at the 99th percentile of exposures 

were determined by taking the difference between the aggregate (food+ drinking water)

exposures and the food (alone) exposures for each population subgroup. Acute drinking water 

exposure U.S.population resulted in a MOE of 30,084 (0.3% of the aRfD of 0.25 mg/kg-bw/day). 

The most exposed sub-population was children 1-2 years old with a MOE of 19,592 (0.5% of the 

aRfD of 0.25 mg/kgfday). Since the benchmark MOE for this assessment was 100 and since EPA 

generally has no concern for exposures below 100% of the aRfD,Syngenta believes that there is 

a reasonable certainty that no harm will result from acute drinking water exposure to residues 

arising from all registered and proposed uses for difenoconazole.

Chronic Exposure from Drinking Water. The chronic surface water EDWC of 13.5 ppb was input 

directly into the DEEM-FCID software as "water,direct and indirect,all sources"to model the 

chronic drinking water exposures. Chronic drinking water exposure to the U.S.population 

resulted in a MOE of 3,396 (2.8% of the cRfD of 0.01mgfkg-bw/day). Chronic drinking water 

exposure to the most exposed sub-population (all infants,<1year old) resulted in a MOE of

1,317 (7.3% of the cRfD of 0.01mg/kg-bw/day). Since the Benchmark MOE for this assessment 

was 100 and since EPA generally has no concern for exposures below 100% of the cRfD, 

Syngenta believes that there is a reasonable certainty that no harm will result from chronic 

drinking water exposure to residues arising from all registered and proposed uses for 

difenoconazole.

2. Non Dietary Exposure: The use of difenoconazole on ornamentals and flower 

gardens (Inspire•,Ready-to-Use spray) and golf courses (Quadris Top'M,Heritage TopTM, 

Briskway'M) may result in residentialhandler or post-application exposures to selected 

subgroups. A short-term toxicological dermal and inhalation endpoint of 1.25 mg/kg-bw/day 

was selected based upon the no observed adverse effect level (NOAEL) from a 2-generation

reproductive study in rats with an uncertainty factor of lOOX,which includes intra- and interspecies variations;no additionalFQPA safety factor was applied. Exposure values were

expressed in terms of margin of exposure (MOE),which was calculated by dividing the NOAEL by 

the exposure for each subgroup. Adult gardeners 19+ years old had a short-term residential 

MOE of 249 and youth gardeners had a short-term residentialMOE of 363;there were no other 

exposed subgroups. Since the Benchmark MOE for this assessment was 100 and since the EPA 

generally has no concern for exposures above the Benchmark MOE,Syngenta believes that

there is 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
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Cumulative Exposure toSubstances with a Cammon Mechanism of Toxicity. Section

408(b)(2)(D)(v) requires that,when considering whether to establish,modify,or revoke a 

tolerance,the Agency consider "available information" concerning the cumulative effects of a 

particular pesticide's residues and "other substances that have a common mechanism of 

toxicity". An ongoing series of studies being conducted by the U.S.Triazole Task Force (USTTF) 

are designed to provide the Agency with more complete toxicological and residue information 

for 1,2,4 triazole and two conjugates,triazolylalanine and triazolylacetic 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 

databases. For the purposes of this tolerance action,the EPA has not assumed that 

difenoconazole has a common mechanism of toxicity with other substances.

E. Safety Determination

1.U.S. population. The acute dietary exposure analysis (food plus water) showed that 

exposure from all current,pending and proposed uses of difenoconazole would result in a MOE 

of 699 (14.3% of the aRfD of 0.25 mg/kg-bw/day) for the general U.S.population,which exceeds 

the Benchmark MOE of 100. For the short-term aggregate exposure analysis the corresponding 

food,water and residentialMOEs were aggregated using the inverse MOE approach. The shortterm aggregate (food,drinking water,and residential) MOE was 207 for the generalU.S. 

population,which exceeds the Benchmark MOE of 100. The chronic dietary exposure analysis 

(food plus water) showed that exposure from all current,pending, and proposed uses of 

difenoconazole resulted in a MOE of 943 {10.2% of the cRfD of 0.01mg/kg-bw/day) for the 

generalU.S.population,which also exceeds the Benchmark MOE of 100. Based on the 

completeness and reliability of the toxicity data supporting these petitions,Syngenta believes 

that 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-occupational exposures.

2. Infants and children. The acute dietary exposure analysis (food plus water) showed 

that exposure from all current,pending and proposed uses of difenoconazole would result in a 

MOE of 341{29.3% of the aRfD of 0.25 mg/kg-bw/day) for the most sensitive population 

subgroup, children 1-2 years old,which exceeds the Benchmark MOE of 100. For the short-term 

aggregate exposure analysis the corresponding food,water and residential MOEs were 

aggregated using the inverse MOE approach. The short-term aggregate (food,drinking water, 

and residential) MOE was 438 for children (1-2 years),which exceeds the Benchmark MOE of

100. The chronic dietary exposure analysis (food plus water) showed that exposure from all 

current,pending, and proposed uses of difenoconazole resulted in a MOE of 337 {28.6% of the 

cRfD of 0.01mg/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 reliability 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 other types of non-occupational exposures.

F. International Tolerances
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Codex Alimentarius Commission established Maximum Residue Limits (MRLs) for 

difenoconazole invarious agriculturalcommodities including asparagus, banana,beans,except 

broad bean and soya bean, broccoli,Brussels sprouts, cabbages, head, carrot,cauliflower, 

celeriac, celery, cherries,edible offal (mammalian),eggs,garlic, ginseng, grapes,leek, lettuce, 

head,lettuce,leaf,mango,meat,milks,nectarine,olives,papaya, passion fruit,peach,peas

(pods and succulent/immature seeds),plums (including prunes), pome fruits,potato,poultry

meat,poultry,edible offal of, rape seed,soya bean (dry),sugar beet,sunflower seed,tomato, 

tree nuts, wheat, and wheat straw and fodder,dry.