EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER (11/19/2010) EPA Registration Division contact: [Ho pe Johnson (PM-21) 7 03-305

-5410)



# ~ INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In cases where the outline element does not apply, please insert "NA-Remove" and maintain the outline. Please do not change the margins, font, or format in your pesticide petition. Simply replace the instructions that appear in green and brackets , i. e., "(ins ert company n ame]," with the information specific to your action. 

### TEMPLATE: (Sy ngenta Cro p Protection] [l nscrt petition n um ber] I"P A has

**r~ccived** a pe sticide petition (!in s ert petition num ber]) from [S yngenta C rop Prote ct io n] , (P
. 0. B ox 18300 , Green sboro, NC 2 74091 propo s ing, pursuanr to sec tion 408(J) ofthc Federal Food. Drug. and Cosme t ic Act (ffD CA), 21 U
. S.C
.

**~46a(d** ). to umend 40 CFR p art 180.532. (Options (pick one) 1
. by establishing the tolerances 

### C o r residues 

## or [cyp r odinil: 4 -cyclop ro pyl-6-me thyl-N-ph eny l

- 2-py rimid inamine] in or on the raw agric ult ura l L:om mo dity (] at 

### 11 Nut, Tree, G roup 14-12; at 0.04 ppm with the exceptions of almo nd and pi stach io whi ch will retain their cu rrently esta bli sh ed tolerances of 0.02 ppm and 0.10 ppm, r espe cti vely EPA ha!:> tk tcrmincd that the petition contains data or inf ormatio n regarding the elem ents set rorth in section 408 (d)(2) of FD DCA: htmcver. EPA has not tu lly evaluated the suflicicncy 

## or the suhmitted data at thi s time or "' hcther the data s uppo rts granting of the petitio n. AdJitional data may be needed

**bd'or ~**  EPA rules on the petition
. A. Residue ( 'hemislry I

. Plant meluhuhsm
. Th e metabolism of cyprodinil is adequately understood for the purpo se of the proposed tolerances. Th e metaboli sm of cyprod ini l has been



# - • • 

# SSI2 c har acte rize d in pl an t s an d anima ls. N o to xic olo gic a U y significant metab o lit es have bee n ident i fie d. T he metab o li s m p r o fil e suppo rt s th e us e of an ana l yt ical e nfo rc em en t me thod that ac c ount s for only parent cypro dinil. 2 . A naZvti c al me t h o d. Sy ngenta C r op Pro tect ion has develo ped and va li da ted ana l yti cal meth odolo gy f o r enf orc em ent purpose s . This me t h od ( Synge n ta C rop P rote cti on Me tho d A G -631B) b as pas sed an Age ncy pet it io n meth od validati on fo r severa l co mm odit i es and i s current l y t he enforc emen t method fo t · cypr odinil. A n ext en si v e dat abase o f meth od v alidat ion da ta u sin g this me tho d on va r ious cro p c ommo di t ies i s availa b l e. 3 . M a g nit ude (J.fresidues. Comp lete residue da ta to support the r eq uested to l erances have bee n su bmit ted. The requested to l erances are adequately supported. In support of the r equ est ed tolerance, S yng enta has conducted the necessary t r i als in ac cord anc e w ith t h e r equirem en t s of the E PA Resi du e Che mist ry Guid eline s 860 .150 0 to dete rmine the magnitu de of res idue o f cy p rod inil in or on re ques t ed commo d it i es . 13. Toxicological Profile EP A ha s eva l u at ed the av aila b l e tox . i city dat a a nd c onsi dered its validity. c om pleteness . an d reliab ilit y as wd.l as the rel ati o nshi p of the results of the s tudies to h uman ri sk . .EP A

h as als o c o n s id er ed av ai lable inf ormat i o n co n ce rnin g the variabi li ty of t h e sens i t i vit i es of m a j o r id e n tifia ble subgr o up s of c ons u me r s , in clu ding infant s an d chil d ren . Spec ifi c

i nforma t i on on t he st udi es receive d and the nature of the to x i c eJTec t s caused by cy p rodi n i l as we ll as the no-observ ed- adverse-effect -l eve l (NO AEL ) fro m lh e t oxic i ty st u dies c an be found at the fo ll o wing we b site: http: //e d o ck et. a cc e ss . g po. g ov / 2 0 12/ 2 0 1 2- 20 23 5.h t m. A su mmary of the t oxi colo gic al e nd p oint s for cyprod inil us ed fo r h uman ri s k asses s ment is disc u s sed in l Jnit fli . A an d B. of the f in al r u l e published i n the Federal R egister oC A ug ust 17.20 1 2 (7 7 FR p ag es 4 9732-49738) (F RL- 9359-7). 1 . A cute**tox ici** **~~· .** **[In~er t**  t ex t. ] 2. Genotoxicty. [Ins ert text.] 3. Reprodu cti ve and developme uta l**toxici~ v.**  [ Inser t text.] 4 . Suhcllronic**toxici~r .**  [Ins ert text.] 5 . Chr o 1tic to xicity . [Ins ert tex t.] 6 . Anima/metabolism. [ Ins ert tex t .] 7. Me taboli te toxicolog y . [Ins ert text . ] 8 . Endocrine dis r uption . [ Insert text . I3

1. Dierury exposutl!. Tier II acute and chronic dietary exposure evaluations were perf ormed for cyp rodinil using the Dietar-y Exp osure Evaluation Model (DEEM

FCIDn• Version 3
. 16) fro m Exponent and consumption data fro m the USDA NHANES "What We Eat in America" survey, 2003-2008. T he se cypro din il exposure asse ssments included all regis te red uses (including almond and pistachio), all pending uses, and proposed n ew uses on Tree Nuts Crop Group 14-12 {p ec an and filb ert)
. Thes e as sessme nts utilized residue data f r om field trials where cyp rodinil was applied at the maximum intended use rate and samp le s were harve sted at the minimum pre-harvest interval (PHI) to obtain maximum re sidues. Em pirically derived processing factors were used in the s e assessments when av ailable; all other processing factors used the

**DEEM-FCID'~'" 1**  Version 7.87 defaults. The percent of crop treated value was assu med to be 100% for all commodities. Secondary residues in beef liver and kidney were estimated based on " maxi m um reasonably balanced diets" and transfer inf ormation fro m feeding stu dies. Drin king water estimates were incorp orated directly into the acute and ch ronic dietary exposure as sessments usin g the highes t estim ated drinki ng water concentratio ns (EDWCs) for surface and ground wa ter. i. 

### Food. Acure ex1w.wre. Th e acute dieta ry (food only) ris k asses sme nts for cyprodinil were performed for all population subgroups using an acute reference dose of 2.0 mg/ l<g- bw/ day based up on an acute neurotoxicity stu dy in r ats with a no observed adverse effect level (NOA EL) of 200 mg/kg-b\Y/ day and an uncertainty factor of 1 

### OOX to account for intra- and inter-s peci es variations. No additional FQ PA safety factor was ap plied. Fo r the purpose of the ac ute aggreg ate risk assessments, the exposure value s were expressed in terms of ma r gin of exp osure (MOE), which was calculated by dividing the NOAEL by the exposure for each population subgro up. In ad dition , exposure was expres sed as a percent of the acute reference do se (%aRID). At the 99
. 9 1h percentile, acute (food only) exposure to the U.S. population resulted in a MOE of 3,154 (4.2% of the aRfD of 2.0 mg/kg-bw/day). The most exposed s ub-population was all infants <1 year old with a MOE of 1,537 (8.7% of the aRID of 2.0 mg/kg-bw/day). Since the Benchmark MOE for this assessment wa s 100 and since the EPA generally has no concern for exposures above the Benchmark MOE or below 100% of the aRID, S yngenta beli eve s that there is a reasonable certainty that no harm will result from dietary (food only) exposure to residues arising from all curr ent, pending , and proposed uses of cyprodinil. ( 'hron ic t>xposure. Th e chronic reference dose (Rf'D ) for cyprodinil is 0.027 mg/kg-bw/day, based on a chronic rat study with a NOAEL of 2.7 mg/kg

bw/da y and an uncertainly factor of 

### lOOX for intra- and inter-species variations. No additional FQJ>A safety factor was applied. For the pu rp ose of the ag gregate risk assessment, the exposure values were express ed in terms of ma rgin of exposure { MOE), which was calculated by dividing the NOAEL by the expos ure for each population subgrou p. In add ition, exposure was expressed as a percent of the4 chronic referen ce dose (%c RfO ) . C hr o nic (food o nly ) ex posure to the U . S.

popul a tion resulted in a MO E of 797 (12. 5 % of the cRID of 0 . 027 mglkg- bw/ day ).

The m ost exposed su b - pop ulat i on w as chil dren 1 - 2 years old with a MOE of 274 (36.5% of the cR fO of 0.027 mg!kg -bw/ da y). Sin ce the Benc hmark MOE fo . r this as ses sment w as 100 an d since the EP A generally has no concern for exposures above the Benc hma rk MOE or below 100% of the c RfD , Syngenta belie ves that there is a reasonable cert ain ty that no ha rm w ill result fro m d ieta ry (food on ly ) exp osure to residues arisi ng from all current, pending, and proposed uses of cyprodin il . Cancer. Cyprodinil is cla ssifie d as 44 not likely " to be ca rcin ogenic to hum ans . Therefore, a cancer risk assessment was not performed for cyprodinil . ii. Dri nkin g water. The Estimated Drinking Water Conc en tration s (ED WCs) of cypro di nil and its dcgradate CGA249287, reported as combi n ed tota l resi dues (cypro dinil plus CGA249287), were det er mine d for currently r egist ered uses (incl u ding almon d an d pi stachi o), all pend in g use s, an d proposed us es for

rep res entative crops of Tree Nut Crop Group 14-12. The Tier I SCI-GROW (version 2.3) m ode l was used to es tima te gro und water concentratio ns , an d the Tier II Surf ace Water Concentration Calcul at or (v. 1..106) was use d to es timat e su rfa ce water concentrations. For ground water, the cu rr ently registered uses on a lm ond and gr apes provided a co mbin ed ED WC of ().086 ppb ( ac ute an d ch roni c) . For s urface water, the registered us e on grapes provided a co mbine d acute ED WC of 48.2 ppb and a com bine d chronic ED WC of 25 . 5 ppb. No Percent Cropped Area adjustm ents were ma de to the sur fa ce water EOWCs. Sin ce the sur face water ED WCs exceed the gro und water ED WC, surface water values were tls ed for ri sk ass essme nt purposes and considered protect i ve for any ground water exposure con cerns.

Ac ute Erposurefi·om Drinking /-Vater: The acu te surface water ED WC of 48.2 ppb was inp ut directly int o the DEEM-FCJDTM software as " water, direct and indir ect,

all sou r ces" to mo de l the acute dri nking water exp osu res . The acute dr inking water · exposure contributio ns at the 99.9 1 h percentile of exposures was det er mine d by taking the d ifferenc e betwee n the aggregate (food + drinking water) exposures and the food (only) expo sures for each popul at ion subg r o up . Ac u te drinking water exposure to the U . S. popu lat ion re sult ed in a MOE of 144,404 (0.1% ofthe aR ID of 2.0 mglkg

- bw/ day ). The most sensitive subpopu l ati on was chil dren 6 - 12 y ear s old, wit h a MO E of 143,266 (0.1 (Yo of the a RID of 2.0 mglkg-b w/day) . Since the Benchmark MOE for this assessment was 100 and since the EP A generally has no conc er n for exp o sur es above the Benchmar k MOE or below 100% of the a RID , Sy ng en ta b eli eves tha t the re is a re as onabl e cer taint y tha t no har m will result from acute dri nking water exposure to residues ari sing from alJ curre n t, pendin g, and proposed uses of cypro dinil.

Chronic E'-C posurefrom Drinking J · Vater: The chr o nic surface water ED WC of 25 . 5 ppb was in put dir ect ly int o the D E EM . -F CIDTM software as Hwater, direct and indirect, all sou r ces" to mo del th e chr o ni c dr inl<in g water exposures. C hronic5 d rinking water expo su r e to th e U.S
. populat ion resulted in a MOE of 5,057 (2.0% of the cRfD of 0.027 m glkg- bw/day). The mo st sensi tive subpopulat ion w as a ll infants (< 1 year o ld), w ith a M.OE of 1 ,96 1 (5. 1 % of the cRfD of 0.027 mg/kg

- bw/day). Since the Benchm arli. MOE for thi s asses sm ent was 100 a nd since th e EPA generally h a s no concern for exp osu r es above the Benchmark M OE or below 1 00% of the cRfD, Syngenta believes th at there is a r easonable certainty that no harm will res ult from chronic drin k ing water ex p o sure to residues ar is in g f ro m all c ur rent, pen din g, an d propo sed uses of cypr ·odinil. 2
. N on-die tary exposur e . Cyprodin il is not cu rrently r egister ed fo r any uses th a t w ould result in residential handler (mixer/loa d er/applicator) expo sure. The product labe l for Palladi um®, containing cy prodin il and .fludioxonil , allows p r ofessional appl ications to orna me nta l plan ts in residen tial settings . No post-applicat ion re sidential expo su r e asses s men t is required because post
-application exp osure to a d u lts and chi ldren fro m orn amenta l app lications is negligible
. Resi d ent ial exposure as s es s m en ts we r e p erform ed for cy p rodin il to evaluate expo sure s resu lting from off

site drift of a gric u ltural p r od u cts in to residential areas. Incidental exp osure to consumers fro m spray d rift from non-resid en t ial u ses wer e not included in the a ggreg ate cons u mer ris k ; this approach a grees with th e EPA's cur r ent po licy and practice. D. Cwmr/ative ljfi:cts 

### Cumu lative E x

posure to Substances W ith a Common Mechanism ofToxicity. Secti on 408(b)(2){D)(v) requ ires tha t, when cons id erin g w hether to establish , mod if y, or revoke a tolerance, t he Agency consider "available info rmation" concer ning the cumul at ive ef fec ts of a partic ular p esticide's r esidues and "other substances th at have a common mechan ism of toxicity"
. Th e EPA d oes not have, at this time , availab le da ta to dete rmine wh ether cyp rodinil has a com m on m echanism of toxicity with other su bstan ces or how to include this pesticide in a cumu la t ive r isk asses sme nt. F or the pu rp oses of thi s tolerance action, the EPA has not a ss umed that cyprod in il has a co mmo n mec han ism of toxicity with other substan ces . 

### E Sc{ /etv Dc: ta mino/ ion . 1. (

_ !.S. pop ula t io n. T h e acute dieta ry exposure ana lysis (food plus w ater) sh ow ed that exposure fro m a ll cu rrent, pe nd ing, and proposed uses of cyp rod inil w ou ld r esult in a MOE of 3,086 (4
. 3% of the aRID of 2.0 mg/kg- bw/ day) for the genera l U .S. population, which exceeds th e Benc hm ark M OE of 100. Th e chro n ic dietary expo sure ana lys is (food p lus wa ter) show ed tha t ex p os ure f rom a ll c urrent, pending, a nd p r oposed u ses of cypro dinil r es u lted i n a MOE of 688 ( 1 4
. 5% of the cRf D of 0
. 027 mg/kg-bw/day) for the general U.S
. population, wh ich also exceeds the Ben ch ma rk M O E of 100
. A cancer expo sur e analys is w as not p erf ormed , si n ce th ere is no evidence of h u ma n carcinogenic poten tial for cy prod in il
. B ased on th e completeness and r eli a bility of the toxicity data supporti ng th ese petiti ons, Syngenta believ es that th ere is a reasonable certainty that no h arm will re sul t from aggreg a te6 expos ur e to residues a r i sin g from a ll cu r rent, pendi ng, a nd proposed us es of cypro d inil . 2 . lnjhnt s aiUl children . The acute dietary exposure an alysis (food plus water) showed that exposure from all current, pending, a nd proposed uses of cyprod inil resulted in a MOE of 1 , 523 (8.8% of the a RID of 2 . 0 mg/l<g

- bw /da y) for the m ost sensitive population subgroup, a ll in fants <1 ye a r o ld , w hi ch exceeds the Benc hmark MOE of 100. The chronic a gg reg at e die tar y (food p l u s water) exposure analysis showed that e xp o sur e fro m all current, p ending , and proposed us es of cyprod in il wou l d resu lt in a 2 5 4 (39.4 ( % of the c RfD of 0.027 m g/ l< g

- bw/ da y) for the m ost sensit ive pop ulat ion subgroup, c hil dren 1-2 years old, which e x c e eds th e Benchmark MOE of 100 . A can ce r ex posure ana lysis was not perfor me d, since there is no eviden ce of h uman carci n oge n ic potential for cypro dinil . Ba s ed on the co m plet enes s an d r eliability of

the t oxicity data supporting thes e petitions, Syngcnta b elieves t hat there is a r ea sonab l e certa in ty tha t no harm will result to infant s and c hil dren f rom ag gregat e expo s u r e to resi d ues ar i sin g fr om all current, pendi n g, and proposed u ses of cyprodin i l. 3 . F e mal es J 3 - 4 9 y ear s of a g e. The acute ag g r egate exposure ana lys i s showed that expos ur e to all c u n·ent and proposed cyprod inil u ses would res ult in a MO E o f 3,185 (4 . 2% of the aR ID of2 . 0 m glk g -bw /da y) for fe ma les 13-49 y ea rs old, which exceeds t h e Benc hma rk MOE of l 00. T h e chr oni c a gg re ga te e xp os ur e an al ysis sho wed tha t ex pos ur e to all c ur rent and proposed c y p r o dinil u ses would res ult i n a MOE of 769 (13.0% of the c RfD of 0 . 027 mg/kg-bw/day) for females 13 - 4 9 years old, w hich exce eds the B enc hmark MOE of 100 . A c anc er exposure analysis was not perfor med , sin ce there is no evidence of h uma n carci n og en ic potential for

cypro d in il . B ase d on the comple tenes s and r e liability of the toxicity data supporting these petiti ons , S yng en ta believes that there is a r eas onable certa inty that no har m w ill res ult from aggr egate exposure fr o m all curr ent , pen din g , and proposed us e s of cyprodinil. F . lnfern a fi olla l T ol er on ces Codex Alim e n tarius Co mmis sion est ablis hed Ma xim um R esi due Limit s ( MRL s) for cyprod inil in or on various a gri cult ural co mm odities in clu ding almond b ulls , almonds, apple, barley , b e a ns (except broad bean an d soy be an ), cucumber, dried g ra pes (curr ant s , rai sin s , and s ult an . as), e d ible offa l , e gg plant, grapes, lettuce (head and le af) , bu lb o nion , pear, sw e et peppers, pr une s, raspberries (red an d bla ck) ,

su mm er squ ash , stone f rui ts, straw and fodder of cereal g rai ns, strawberry, to ma to, wheat, and various m e a t, milk, and eg g c omm odities .