Document ID: EPA-HQ-OPP-2012-0575-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-12-19T05:00Z

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 petition number])  from
[Syngenta Crop Protection],[P.0. Box 18300,Greensboro,NC  27409] prop 
ng. pt	u 	t to s.._.to..408 -. 	te r-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 	c1,2,4,-triazole)] in or ot   he rav..	r.cultural commodtty
[vegetables,

                     ro	[0.01]	[4.0]	                   

2.  by removtn 	•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D 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 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.

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 combination end-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 Trial Regions for potatoes in Zones
1,5,7A,12,and 14. At all sites,Difenoconazole/Fiudioxonil 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 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'l detect 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 no

1. Acute toxtcl 	(NA-Remove]

2. Genotoxicty  [NA-Remove]

3 Reproductive and developmental tOXIC/tD (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

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-FCID™),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 (Crop
Group 8),grapes, mango (imported),papaya (imported),pome fruit (Crop
Group 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 small grains 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 B11.3x),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         
                          

percent of the acute reference dose (%aRfD). At the 99.91 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/kg100 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 "'	'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	B0.0104 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 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 toxicologicaland 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

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,pending and 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.