EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS 

PUBLISHED IN THE FEDERAL REGISTER (1/18/2011)

EPA Registration Division contact:[Rosemary Kearns,(703)305-5611]

[Syngenta Crop Protection LLC.]

[Insert petition number]

EPA has received a pesticide petition ([insert petitionnumber]) from [Syngenta 

Crop Protection],[P.0.Box 18300,Greensboro,NC 27409] prop ng. pt u t to 

s.._.to..408 -. ter-ece a Foo ug,an_ osmet c .._t ,FFDCA),21U.S.C. 346a(d), 

to amend 40 CFR part 180.180.

(Options (pick one)

1. o c·eas·-- .....e estab '-'ied tote ce fo · ues o [Difenoconazole :1[2-

[2-chloro-4-(4-chIorophenoxy)]phenyl-4-methyl-1,3-dioxolan-2-ylmethyl]-1H1,2,4,-triazole)] in or ot he rav.. r.cultural commodtty [vegetables,

 ro [0.01] [4.0]

2. by removtn •· e es _.... t·hed •ole ce r ne raw agncultl.ra:

commodit [potatoes, processed waste] a [0.04] parts per mtll:on (p m).

EPA has determined that the petitton contains data or information regarding the elell'e'lts set 

forth m sectton 408 (d)(2} ofthe FDDCA;however,EPA has not fully evaluated the :u:fn..• ncy of 

the submitted data at thts time or whether the data supports granting of the pet1t1r•. Additton'll 

data may be needed before EPA rules on the petition.
A. Residue Chem1stry

Pia 1 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 

phenyland triazole labels in wheat,tomatoes,potatoes,grapes,and spring rape. The metabolic

pathway was the same in these four separate and distinct crops. Therefore, the metabolism of 

difenocoanzole is considered to be adequately understood for all crops,per EPA Test Guideline

860.1300.

"10 .. i. Food. Syngenta Crop Protection,Inc. has submitted a practical 

analytical method (AG-575B,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 monitoringof 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,forthe 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.

11. 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 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 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 Mogmtude of res1dues. Sixteen potato residue trials were completed in Canada to 

determine the magnitude of the residues of fludioxonil,difenoconazole,and CGA 205375 in or 

on potato tubers after a seed treatment application of Difenoconazole/Fiudioxonil FS (a 

Canadian combinationend-use product containing 19.4 g/l(0.16 lb/gal) difenoconazole and

19.4 g/l(0.16 lb/gal) fludioxonil).Site Selection was determined according to the geographic

Canadian Major and Minor Crop Field TrialRegions for potatoes in Zones 1,5,7A,12,and 14. At 

all sites,Difenoconazole/FiudioxonilFS was applied at 2.5 g Difenoconazole and 2.5 g Fludioxonil 

per 100 kg (220 lb) of potato seed pieces. At two sites additional samples were collected to 

demonstrate residue decline. Potatoes were harvested 75-129 days after the plandng ot the 

treated potato seed pieces.

The residue of Difenoconazole in these samples ranged from no detect to 0.036 ppm except or.e 

sample which had residues of 0.096 ppm. The residues of CGA-295375 varied from n'ldetect to
0.043 ppm. Therefore,Syngenta is proposing that difenoconazole tolerance on tuberous and 

corm to be increased to 0.07 ppm to cover this use.

B.Toxicologtcal Profile

EPA has evaluated the ava1lable tox1c1ty data and cons1dered 1ts validity, completeness. and 

rellabrllty as well as the relat1onshrp of the results of the stud1es to human nsk EPA has also 

considered available rnformat1on concernrng the vanab1hty of the sens1tiv1t1es of major

1dentif1able subgroups of consumers,rncludmg rnfants and children. Specific mformation on the 

stud1es recerved and the nature of the tox1c effects caused by difenoconazole as well as the noobserve· ac r e-effe "JO;..EL n the to( :.tud1es can be found at the followmg 

website http://edocket.access.gpo.gov/2008/E8-15.htm A summary of the toxicolog1cal 

endpoint to difenocon ole Jsed tor h man ns L e_s.nent rs d1scussed In Un1t III.B. of the 

frnalrule published in the FederalReg1ster of January 09,2008 (73 FR 1503) (FRL-8343-5).

1. Acute toxtcl (NA-Remove]

2.Genotoxicty [NA-Remove]

3 Reproductive and developmental tOXIC/t} (NA-Remove)

4.Subchromc toxiC/ [NA-Remove]

5.Chrome toxiC/ (NA-Remove]

6.Ammo/ metaboltsm [NA-Remove]

7 Metabolite toxiCology [NA-Remove]

8.Endocrine disruption (NA-Remove]

C. Aggregate Exposure
h

P " Tier III/IV acute,short-term,and chronic aggregate exposure evaluations were 

performed for difenoconazole ([(2$,4R)/(2R/4S)]/[(2R/4R)/(2S,4S) 1-(2-[4-(4-chlorophenoxy)-2-

chlorophenyl)-4-methyl-1,3-dioxolan-2-yl-methyi)-1H-1,2,4-triazole) using the Dietary Exposure 

Evaluation Model(DEEM-FCIDTM),version 2.16 from Exponent. These exposure assessments 

included all current and pending uses as well as an increased domestic tolerance to 

accommodate the proposed new seed treatment use on imported potatoes grown in Canada 

from potato seed pieces treated with Maxim DTM brand fungicide product containing 

difenoconazole. Difenoconazole is currently registered for seed treatment uses on barley, 

canola,sweet corn,wheat, and imported rye,and for foliar uses on bananas (imported),

Brassica vegetables (Crop Group 5),bulb vegetables (Crop Group 3),canola,citrus (Crop Group

10),cotton,cucurbit vegetables (Crop Group 9),fruiting vegetables (CropGroup 8),grapes, 

mango (imported),papaya (imported),pome fruit (CropGroup 11),sugar beets,tree nuts (Crop 

Group 14),tuberous and corm vegetables (Crop Group 1C),and wax apple (imported). Pending 

uses include carrots, chick peas,soybeans,stone fruit (Crop Group 12),strawberries,and a seed 

treatment use on all smallgrains such as wheat, barley,buckwheat,millet,oats,rye, and

triticale. For the proposed use on potato seed pieces,an amended difenoconazole tolerance of

0.07 ppm was assumed for all potatoes in the dietary assessments. Residue values used in these 

assessments were obtained from residue field trials conducted at the maximum labeled 

treatment rate and harvested at the minimum pre-harvest interval (PHI). Experimental 

processing factors were used for apple juice (0.03x),citrus oil (47x),citrus pulp (4.1x),

cottonseed oil (6.3x),grape juice (0.6x),grape raisins (3.5x),orange juice (0.1x),potato dry

flakes (0.87x),soybean hulls {11.3x),soybean meal (2.2x),soybean oil (12x),sugar beet molasses 

(0.58x),sugar beet sugar (0.33x),tomato paste (1.61x),and tomato puree (0.55x);all other 

processing factors utilized either the DEEMTM (version 7.87) default processing factors or 

theoretical concentration factors listed in OPPT$860.1520. Anticipated residues in meat,milk, 

and eggs were calculated by constructing a theoretical "maximum reasonably balanced diet" 

(MRBD) using the OPPTS 860.1000 Table 1feedstuffs (June 2008 revision). 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. All consumption data for these assessments were taken 

from the USDA's Continuing Survey of Food Intake by individuals (CSFII) with the 1994-1996 

consumption database and the Supplemental CSFII children's survey (1998) consumption 

database.

r ,.. ..u The difenoconazole acute food risk assessment was performed using an 

acute reference dose (aRfD) of 0.25 mg/kg-bw/day based upon an acute neurotoxicity study i11 

rats with a no observed adverse effect level (NOAEL) of 25 mg/kg-bw/day and an unc rtainty 

factor of 100X. The 100X safety factor includes intra- and inter-species variations· .,,., c>cldtiional 

FQPA safety factor was applied. For the purpose of aggregate risk assessment,the t:xposure 

values were expressed in terms of margin of exposure (MOE),which was calculatcc! '::r1 dividing 

the NOAEL by the exposure for each subpopulation. In addition,exposure was ex:')..f'!"Sd 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 1,578 (6.3% of the aRfD of 0.25 mg/kgbw/day). The most exposed sub-population was children (1-2 years old) with a MOE of 628 

(15.9% 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 or below

100% of the aRfD,Syngenta believes that there is a reasonable certainty that no harm will result 

from dietary (food only) exposure to residues arising from all current and pending uses plus the 

proposed use on seed potatoes.

o e The difenoconazole chronic food risk assessment was performed for all 

population subgroups using a chronic reference dose of 0.01mg/kg-bw/day based upon a 

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

(NOAH) of 0.96 mg/kg-bw/day and an uncertainty factor of 100X. The lOOX safety factor 

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

the purpose of 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 subpopulation. In addition, exposure was expressed as a percent of the chronic reference

dose (%cRfD). Chronicfood exposure to the U.S.population resulted in a MOE of 1,774 (5.4% of 

the cRfD of 0.01mg/kg-bw/day). The most exposed subpopulation was children (1-2 years old)

with a MOE of 513 (18.7% 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 or below 100% of the cRfD,Syngenta believes that there is a reasonable certainty 

that no harm will result from dietary (food only) exposure to residues arising from all current 

and pending uses plus the proposed use on seed potatoes.

Concu. 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).

11. Or nJ.-ing W 1 The Estimated Drinking Water Concentrations (EDWCs) of 

difenoconazole were determined using Tier 1screening model SCI-GROW (version 2.3) which 

estimates pesticide concentration in ground water and Tier II PRZM/EXAMS (PE version 5.0) 

which estimates surface water exposures. EDWCs of difenoconazole from the currently 

registered and pending uses and the proposed import tolerance for potatoes were determined. 

For the potato import tolerance,the imported potato is for human consumption only,thus, 

there is no environmentalexposure to ground water and/or surface water. Based on the SCIGROW modeling results,the highest groundwater EDWC for difenoconazole was o.n1

. ppb

(acute and chronic) based on the currently registered citrus use. Based on Tier 1; PRZM/EXAMS 

modeling for surface water conducted by EPA (D367382),the currently registerec! 6: J!.. use 

provided the highest EDWCs of 15.8 ppb and 10.4 ppb for acute and chronic,respect=vely 

(adjusted for 0.87 Percent Cropped Area,PCA). Since the surface water EDWCs e)(t.:...eti t:he

ground water EDWC,the surface water values were used for risk assessment pur u:.cand will 

be considered protective for any ground water exposure concerns.
'"u e "' '·o C'l The peak (acute) EDWC of 15.8 ppb (0.0158 ppm) for 

surface water was input directly into the DEEM-FCIDTM software as "water,direct and indirect, all 

sources"to obtain the acute dietary exposure from water. Drinking water exposures were 

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

and food exposures (food only) for each population subgroup. At the 99.9th percentile,acute 

drinking water exposure to the U.S.population resulted in a MOE of 146,199 (0.1% of the aRfD

of 0.25 mg/kg-bw/day). The most exposed subpopulation was children 1-2 years old,with a 

MOE of 24,728 (0.4% 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 or below 100% of the aRfD,Syngenta believes that there is a reasonable certainty 

that no harm will result from acute exposure to drinking water residues arising from all current 

and pending uses plus the proposed use on seed potatoes.

C o c. re -.o ··(Jl The annualaverage (chronic) EDWC of 10.4 ppb

{0.0104 ppm) for surface water was input into the DEEM-FCIDTM software as "water,direct and 

indirect,all sources" to obtain the chronic dietary exposure from water. Drinking water 

exposures were determined by taking the difference between the aggregate exposures (food+ 

drinking water) and food exposures (food only) for each population subgroup. Chronic drinking 

water exposure to the U.S. population resulted in a MOE of 4,379 (2.2% of the cRfD of 0.01 

mg/kg-bw/day). The most exposed sub-population was all infants <1year old,with a MOE of

1,336 (7.2% 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 or 

below 100% of the cRfD,Syngenta believes that there is a reasonable certainty that no harm will 

result from chronic exposure to drinking water residues arising from all current and pending

uses plus the proposed use on seed potatoes.

- ,e 1 e Difenoconazole is a broad spectrum fungicide used in 

residential applications for landscape ornamentals and materials protection. Difenoconazole is 

formulated in Difenoconazole 2EC for protection of landscape ornamentals and in

DIFENO-Shieldy.. as an additive to paint. For landscape ornamentals,these residentialexposure 

assessments were run in support of registered uses of Difenoconazole 2EC at a maximum single 

application rate of 8.0 oz product/A (0.13 lb ai/A) for prevention of diseases in roses. For paints 

containing DIFENO-Shield.'.,these exposure assessments assumed a maximum application rate 

of 0.01% ai w/w. The toxicological endpoints established by the EPA in the August 2007 HED 

difenoconazole risk assessment were used (NOAEL = 1.25 mg/kg-bw/day). The worse case

short-term margin of exposure (MOE) for all uses assessed was for adults applying paint with ?n

airless sprayer, with a combined (inhalation and dermal) MOE of 387. Since the ;u.iJ.ltiaiiVoOE 

exceeds the EPA's Benchmark MOE of 100,Syngenta believes that there is a rea onablc 

certainty that no harm will result from short-term exposures arising from all current: an1 

pending uses plus the proposed use on seed potatoes.

D.Cumulative Effects
Cumulative Exposure to Substances with a Common 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 (USTIF) 

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 toxicologicaland exposure 

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

difenoconazole has a common mechanism of toxicity with other substances.

E.Safety DeterminatiOn

U 5 Jv,Ju .Using the conservative assumptions described above,and

based on the completeness and reliability of the toxicity data,the acute aggregate exposure

analysis for

all current,pending and proposed uses of difenoconazole resulted in a MOE of 1,561for the U.S.

population. The short-term aggregate exposure analysis for all current,pending and proposed 

uses of difenoconazole resulted in a MOE of 321for adults 50+ years old. The chronic dietary 

exposure analysis for all current,pending and proposed uses of difenoconazole resulted in a 

MOE of 1,263 for the U.S. population. Since the worst case aggregate MOE of 321for shortterm aggregate exposures exceeds the Benchmark MOE of 100,Syngenta believes that there is a 

reasonable certainty that no harm will occur to the U.S.Population from acute,short-term,and 

chronic aggregate exposures arising from all current and pending uses plus the proposed use on 

seed potatoes.

nfa . . Using the conservative assumptions described above,and 

based on the completeness and reliability of the toxicity data,the acute aggregate exposure 

analysis for all current,pendingand proposed uses of difenoconazole resulted in a MOE of 613 

for children 1-2 years old. The short-term aggregate exposure analysis for all current, pending 

and proposed uses of difenoconazole resulted in a MOE of 694 for children 1-6 years old. The 

chronic dietary exposure analysis for all current, pending and proposed uses of difenoconazole 

resulted in a MOE of 437 for children 1-2 years old. Since the worst case aggregate MOE for 

chronic exposures of 437 for children 1-2 years old exceeds the Benchmark MOE of 100, 

Syngenta believes that there is a reasonable certainty that no harm will occur to infants and 

children from acute,short-term,and chronic aggregate exposures arising from all current and 

pending uses plus the proposed use on seed potatoes.

F. lnternatJonal Tolerances

Codex Maximum Residue limits (MRLs) for residues of difenoconazole per se have o;;n 

established on a number of commodities including banana,grapes,meat milk eggs. rnil'<s, 

peach,plums,pome fruit,potatoes,soybeans,tomatoes,and wheat.