### EPA REGISTRATION DIVI S I O N COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS

PUBLISHE D IN THE FEDERAL REGISTER ( 1/18/2011 ) EPA Registration Division contact : [Rosemary Kearns , (703)305 - 561 1 ]



### [ Syngenta Crop Protection LLC

. ] [I ns e rt petitio n number]

EPA has received a pesticide petition ([insert petitio n num be r]) from [Syngenta Crop Protection] , [P . 

### 0 . B o x 18300 , Greensboro , NC 27409] prop ng . pt u t to s. ._.to . . 408 - . te r-ece a Foo ug , an_ osmet c . .



### _ t , FFDCA) , 2 1 U.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-ch I oro phenoxy)] p henyl -4 - meth y l - 1,3-d ioxo la n -2- yl methyl] - 1

H1 , 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: c ommodit [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 pet1t1 r •. 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 1 4 C -difenoconazole has been studied using both phenyl and triazole labels in wheat ,tomatoes , potatoes , grapes , and spring rap e . 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 P rotect i on , Inc. has submitted a practical analytical method (AG - 575B, master record identification (M R ID) No. 428065-04) for detecting and measuring levels of difenoconazole in or on food with a limit of quantitation (LOQ) that allows monitorin g of food with residues at or above the leve l s set in the proposed tolerances. EPA has validated this method and copies have been provided to FDA for i nsertio n into pesticide analytical manual (PAM) II. Method REM 147.08 (MRID 46950222) is also available for enforcem e nt metho d , fo r 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.

11. Livestock. Syngenta Crop Protection , In c . has sub m itted 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 inte re sted , and may be o btained from the Field Operations Divisio n , Office of Pesticide Programs. To l e ra nces 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 combination end - use product contai n ing 19.4 

### g/l (0.16 lb/gal) difenoconazole and 19.4 

### g/l ( 0

. 16 l b

/g a l) fludioxonil )

. Site Select ion was determined according to the geographic Canadian Major and Minor Crop Field Tria l Regions for potatoes in Zones 1 , 5 , 7A , 12 , and 14. At all sites ,Difenoconazole/Fiudioxoni l FS 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 7 5-129 days after the plandng ot the treated potato seed piece s . The residue of Difenoconazole in these sam p les ranged from no detect to 0.036 ppm except or.e sample which had residues o f 0.096 ppm. The residues of CGA-295375 varied from n' l detect to0.043 pp m . Therefore , Syngenta is proposing that difenoconazo l e tolerance on tuberous and corm to be increased to 0

. 07 ppm to cover this us e . 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 vana b1 hty of the sens1tiv1t1es of major 1dentif1able subgroups of consumers , rncludmg rnfants and childre n . Specific mformation on the stud1es recerved and the nature of the tox1c effects caused by difenoconazole as well as the n oobserve· 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 II I . B . of the frna l rule published in the Federa l Reg1ster of January 0 9 , 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 (N A-Remove] C. Aggregate Exposureh P " Tier III/IV a cute , short-term ,and chronic aggregate exposure evaluations were performed for difenoconazo l e ([(2$,4R)/(2R/4S)]/[(2R/4R)/(2S,4S) 1 - (2 - [4 - (4 -chlorophenoxy)-2- chlorophenyl) -4 - methy l - 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 cu rrent and pending uses as we ll 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) , can o la , citru s (Crop Group 10) ,cotton , cucurbit vegetables (Crop Group 9), fruiting vegetables (Crop Group 8) , grapes, mango ( imported ) , papaya (imported) , pome fruit (Crop Group 11) ,sugar beet s , tree nuts (Crop Group 14) , tuberous and corm vegetables (Crop Group 1C) , and wax apple (imported). Pending uses include carrots, ch ick peas , soybeans ,stone fruit (Crop Group 12) , strawberries , and a seed treatment use on all small grains such as wheat, barley , buckwheat , millet, oats , rye, and tritical e . 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) ,soy bean hulls { 11.3x) , soybea n 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 , mil k , and eggs were cal culated by co nstructing a theoretical "maximum reasona b ly bala nced diet " (MRBD) using the OPPTS 860.1000 Table 1 feedstuffs (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 wate r . All consumption data for these assessments were taken from the USDA's Continuing Survey of Food Intake by individuals (CSFII) wi t h the 1994 - 1996 consumption database and the Supplemental CSFII children's survey (1998) consumption databas e . 

### r ,.. . .u The difenoconazole acute food risk assessment was performed using an acute refere n ce dose (aRfD) of 0.25 mg/kg - bw/day based upon an acute neurotoxicity study i 1 1 rats with a no observed adverse effect level (NOAEL) of 25 mg/kg - bw/day and an unc rtainty factor of 100X. The 100X safe ty factor includes intra - and inter-spe cies variations· .,,., c>cldt i io n a l 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. popul a tion resulted in a MOE of 1 ,57 8 ( 6.3% of the a RfD 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 bel ow 100% of the aRfD , Syngenta believes that there is a rea sona b le certainty that no harm will result from dietary (food only) exposure to residues a r ising 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 subgro u ps using a chronic reference dose of 0

. 0 1 mg/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 ri s k assessmen t , the exposure va lues were expressed in terms of margin of exposure ( MOE ) , which was cal culated 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 ex posure to the U.S. population resulted in a MOE of 1,774 ( 5 . 4% of the cRfD of 0.0 1 mg/kg - bw/day). The most exposed s u bpopulation was c h ildren (1 -2 years old) with a MOE of 513 (18

.7% of the cRfD of 0.0 1 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 cRfD , Syngenta believes that there is a reasonable certa inty that no harm will result from dietary (food only) exposure to res idues arising from all current and pending uses plus the proposed use on seed potatoe s . 

### Concu . A cancer dietary assessment was not conducted. Difenoconazole is classified as a Group C, "possi ble human carcinogen/' with a no n- l inear (MOE) approach for human risk characteri zation (CPRC Document , 7/2 7/94 , Mem o , 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 usi ng Tier 1 screening model SCI -GROW (ve r s i on 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 im port to l e rance , th e impo rted potato i s for human consumption o n l y , thus, there is no en v ironmenta l exposure to ground water and/or surface wate r. Based on the SC IGROW modeling results , th e highest groundwater EDWC for difenoconazole was 

## o. n 1

. ppb (acute and chronic) based on the currently registered citrus use . Based on Tie r 

### 1 ; PRZM/EXAMS modeling for surface water conducted b y EPA (D367382) , the currently reg istere c! 6: J!.. use provided the highest EDWCs of 15.8 ppb and 10.4 ppb for acute and chronic , respect=ve ly (adjusted for 0.87 Percent Cropped Area , PCA). Since the surface water EDWCs e)(t. :.. .et i t:he ground water EDWC ,the s urface water values were used for risk assessment pur u:.cand w il l 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 softwa re as "wate r, direct and indirect, all so u rces" 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 subg roup. At the 99.9th percentile ,acute drinking water exposure to the U. S

. population re sulted 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 certa inty that no harm will result from acute exposure to drinking water residues arising from all current and pending uses plus the proposed u se on seed potatoes. 

### C o 

### c. 

### re - .o · ·( Jl The annual average (c h ro n ic) EDWC of 10.4 ppb {0. 0104 ppm) for surface water was input into the DEEM - FCIDTM software as "water , direct and indirect , a ll sources" to obtain the chronic dietary exposure from water. Drinking water exposures were determi n ed by taking the difference between the aggregate exposures (food+ drinking water) and food exposures (food only) for each population s ubgroup. 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- po pulation was all infants < 1yea r ol d , wit h a MOE of 1,336 (7.2% of the cRfD of 0.0 1 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 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 addi t i ve to pain t . For landscape ornamentals , these res ide nti a l exposure 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 pain ts containing DIFENO- Shiel d . ' . , thes e 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 we r e used (NOAEL 

### = 1.25 mg/kg - bw/day). The wor se 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 .ltiaiiVo O E exceeds the EPA's Benchmark MOE of 100 , Syngenta believes t hat there is a rea onablc certainty that no ha rm will result from short-term exposures arising from all current: an1 pending uses plus the proposed use on seed potatoes. 

### D. Cumulative EffectsCumulative Exposure to Substances with a Common Mechanism of Toxicity. Section 408(b)(2)(D)(v) requires that , when considering whether to establish , modif y , or revoke a tolerance , the Agency consider "available informatio n " concerning the cumulative effects of a particular pesticid e's residues and "othe r substances that have a common mecha n ism 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 com p l ete toxicological and residue information for 1,2,4 triazole and two conjugates , triazolylalanine and triazo l yl acetic aci d , 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 toxicologica l 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 . Safet y 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 1,56 1for the U.S. population. The short-term aggregate exposure analysis for all current , pending and proposed uses of difenoconazole resu l ted in a MOE of 32 1 for 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 32 1for 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 , pen d i ng and proposed uses of difenoconazole resulted in a MOE of 613 for children 1 -2 years old. The short-term aggregate exposure ana l ysis for all current, pending and proposed uses of difen oconazole 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 o l d . Since the worst case aggregate MOE for chronic exposures of 437 for children 1 -2 years o l d 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 potatoe s . F. lnternatJonal Tolerances Codex Maximum Residue limits (MRLs) for residues of difenoconazo l e per se have o;;n established on a number of commodities including banana , grapes , meat milk egg s. rnil'<s, peac h , plums , pome frui t , potatoes , soybeans ,tomatoe s , and wheat.