EP A BIOPESTICIDE S AN D POLLUTIO N PREVENTIO N DIVISIO N

COMPAN Y NOTIC E O FFILIN GFO RPESTICID E PETITION S PUBLISHE D I N TH E FEDERA LREGISTE R EP A Biopesticide s an dPollutio n Preventio nDivisio ncontact : [Lind aHollis . 703

- 308-8733] © 1 INSTRUCTIONS : Pleas e utiliz e thi s outlin e i n preparin g th e pesticid e petition . I n case s wher e th e outlin e elemen t doe s no t apply , pleas e inser t

"NA-Remove " an d maintai nth e outline . Pleas e d o no t chang e th e margins , font , o r forma t i n you r pesticid e petition . Simpl y replac e th e instruction s tha t appea r i n green , i.e. , " j inser t compan y namel, " wit hth e informatio nspecifi c t o you r action . SUBMISSION : E-mai l th e complete dtemplat e to : hollis.iinda@epa.gov . TEMPLATE : [Fin e Agrochemical s Ltd. ] [Inser t petitio n num b er f EP A ha s receive dapesticid e petitio n([inser t petitio nnumber] ) fro m[Fin e Agrochemical s Ltd . c/ o SciReg , Inc. , 1273 3 Director' s Loop , Wo o e l bridge , V A 22192 ] proposing , pursuan t t o sectio n408(d ) o f

th e Federa l Food , Drug , an dCosmeti c Ac t (FFDCA) , 2 ! U.S.C,346a(d) : ' t o amen d4 0 CF Rpar t J80 . . ••• " (Option s (pic k

one ) 2 . t o establis hu nexemptio nfro mth e requiremen t o f atoleranc e fo r (Option s (pic k

one ) 2 , biochemica l pesticid e [Prohydrojasmon ] • Pursuan t t o sectio n 4()8(d)(2)(A)(i ) o f FFDCA , a s amended , [Fin e • Agrochemical s Ltd . c/ o SciReg . Inc. , 1273 3 Director' s Loop , Woodbrktaft.Y ^ •* • * 22192 ] ha s submitte dth e followin g summar y o f information , data , an dcirgjnirJnf e i n* * suppor t o f thei r pesticid e petition . Thi s summar y wa s prepare db > [SciReg . Jiy.^an d iiP Aha s no t

full y evaluate dth e merit s q f th e pesticid e petition . Th e sxinimai^n-Ja y hav e bee nedite db y EP A i f

th e lemiinoloa v use dwa s unclear ; th e summar y coi»i»?iB» d*** . I * —' v "*•"• • extraneou s material , o r

th e summar y unintentionall y mad e th e reade r conc. ! ii*J l> e il >:iat

th e ' . finding s reflecte dEPA' s positio nan dno t th e positio no f

th e petitioner . t ••• •I , (Fin e Agrochemical s Ltd . c/ o SciReg , Inc. , 1273 3 Director' s Loop , Woodbridge ,

V A 22192]'Petitio n Summar y llnser t petitio n number ] A . Produc t

Nam e an dPropone dUs e Practice s I'FA L1800 , a n end-us e produc t containin g 5.25 % prohydrojasmon , i s tblJarl y spraye dont o re dappl e varietie s 7-2 8 day s pre-harves t fo r frui t colo r enhancement. ] ' ft . Produc t

Identity/Chemistr y . ' i . Idenf'U y o f

fhepesticid e an dcorrespondin g residues . |Prohydrojasmq n i s th e syntheti c analo g o f

methy l jasmonate , whic hi s anatura l derivativ e o f jasmoni c acid , anaturally-occurrin g plan t hormone . A petitio n fo r temporar y toleranc e exemptio n accompanie s thi s submission . Residu e dat aar e no t applicable. ] 2 : Magnitud e o f

residue s u i th e tim e o f

harves t an dmetho duse di o determin e th e residue . [N o magnitud e o f residu e (MOR ) studie s hav e bee n conducte dwit h prohydrojasmo n base do n th e lo w toxicit y o f th e activ e ingredien t

(se e Toxicolog y Profile , page s 2-6 ) an dit s structura l similarit y t o anaturally-occurrin g plan t hormone. ] 3 . A statemen t

o f wh y a n analytica l metho do j detectin g an dmeasurin g ilu

- level s o f th e pesticid e residu e arc . no t needed . [SciReg , Inc . i s submittin g apetitio n t o establis ha n exemptio n fro mth e requiremen t o f atoleranc e and , therefore , a n analytica l metho di s no t required. ] «'.' . Mammalia n lexicologica l Profil e ' ' . ? 1 1 h e ful l report s tha t

suppor t thi s petitio n an dwhic har e summarize di nthi s sectio nwer e concurrentl y submitte dt o suppor t th e reques t

fo r a n Experimenta l Us e Permit . ' Prohydrojasmo n Technica l 1 . Acut e toxicit y (oral , dermal , inhalation) ; OPPT S 870.1100 , 870.1200 , 870.130 0 Acut e ora l toxicity , acut e derma l toxicity , an dacut e inhalatio ntoxicit y studie s usin g S D rat s wer e conducte dwit hprohydrojasmo n technica l (PDJ) . Th e acut e ora l Lps o wa s >500 0 mg/k g bod y weigh t i n bot hmal e an dfemal e rats . Th e acut e derma l LDs o o f

PD J i n mal e an dfemal e rat s wa s >200 0 mg/k g body-weight . Th e acut e inhalatio nLCs o o f PD J Ava s >2. 8 mg/ Li nmal e an dfemal e rats .2 . Ey e an dderma l irritation , an dski nsensitization ; OPPT S 870.2400 . 870.2500 ,

870.260 0 Primar y ey e an dderma l irritatio nstudie s wer e conducte dusin g Japanes e whit e rabbits . Sligh t

ey e irritatio n wa s observed . N o irritatio nwa s observe di n th e derma l irritatio n study . Aski n sensitizatio n stud y (Maximizatio nmethod ) wa s conducte dusin g Hartle y strai nguine apigs . N o ski n sensitizatio nwa s observed . 3 . 90-da y subchroni c dietar y toxicit y (rats) ; OPPT S 870.310 0 A 90-da y subchroni c dietar y toxicit y stud y wa s conducte dusin g Fische r rat s (1. 0 male s an d1 0 female s eac hpe r group ) b y administratin g mixe dfoo d(technica l substance ; 0,1000 , 300 0 an d1000 0 ppm , correspondin g t o 0 , 56.9 , 16 8 an d56 6 mg/k g bodyweight/da y fo r males , an d0 , 58.5,17 6 an d58 7 mg/k g bodyweight/da y fo r

females) . I n th e 1000 0 pp mdos e group , bod y weigh t gai nsuppressio nan drelativ e adrena l glan de weigh t

increas e wer e observe di n male s an dfemales ; H b concentratio n decreased ; MC H decreased ; tota l protei ndecreased ; A/ Grati o increased ; relativ e live r

weigh t increased ; an drelativ e kidne y weigh t increase di nmales , i n th e 100 0 pp mdos e groups , foo dintak e decreased ; tota l cholestero l increased ; an dseru mchlorin e decrease di n males . I n females , platele t numbe r decreased ; nitroge na s ure ai nurin e increased ; an drelativ e live r weigh t increased . Th e N o Observe dAdvers e Effec t Leve l (NOAEL ) i nthi s stud y i s considere dt o b e 100 0 pp m(male : 56. 9 mg/k g bodyweight/day ; female : 58. 5 mg/k g bodyweight/day) . 4 . Developmenta l toxicit y (rat) ; OPPT S 870.370 0 Adevelopmenta l toxicit y stud y wa s conducte dusin g S D rat s (2 4 female s eac h pe r group ) vi agavag e administratio n(technica l substance ; 0 , 30 , 12 0 an d50 0 mg/k g bodyweight/day ) durin g day s 6-1 5 o f gestation . I nth e 50 0 mg/k g dos e group , bod y weigh t gai nan dfoo dintak e decrease s wer e observed , an dbod y weigh t gai nwa s suppresse di nth e 12 0 mg/k g clos e group . Fo r fetuses , excessiv e ri b growt hwa s observe dwit hhighe r frequenc y i nth e 50 0 mg/k g dos e group , bu t

skeleta l malformation s wer e no t observed . Malformatio n increase s wer e no t

observe da t

100 0 mg/k g dos e grou p i n apreliminar y study . Therefore , frequenc y o f increas e o f

excessiv e ri b growt hi s no t considere dt o b e a teratogeni c effec t

o f prohydrojasmon . Th e NOAE Li nthi s stud y i s considere dt o b e 8 0 mg/k g bodyweight/da y fo r dam s an d30 0 mg/k g bodyweight/da y fo r fetuses . N o teratogenicit y wa s observed .Genotoxicity ; OPPT S 870.5100 , 870.530 0

A nAme s bacteria l revers e mutatio ntes t an dachromosom e aberratio ntes t usin g Chines e hamste r

lun g cell s wer e conducted . Bot hstudie s wer e negative . (Tabl e 1 ) Prohydrojasmo ni s no t considere dt o b e genotoxic . Tabl e .1 . Summar y o f

result s Tes t

//• / vitr o Revers e mutatio ntes t (±S9 )

Chromosom e aberratio n tes t (±S9 ) Subjec t

S . tvphiiiiuiiii mstrain s TA98 , T A 100 , T A 1535 , TA 1 53 7 E . coli strai n \\P2uvr A

Chines e hamste r

lun g cell s (CHL/IU ) Dos e level s (-S9 ) TA100 . TAJ535 , TA1537 : 2.44 , 4.88 , 9.77 , 19.5,39.1,78. 1 ug/plat e (+S9)TA100 , T A J 535 , T A 1537 : 9.77,19.5,39.1 , 78.1 , 156,313,62 5 ug/plat e (-S9 ) TA98 , WP2/wv4 : 2.44 , 4.88,9.77 , 19.5 , 39.1,78.1 , 15 6 ug/plat e (+S9 ) TA100 . TA1535 , TA J 537 : 39.1,78.1 . 156 , 313 , 625 , 1250 , 250 0 ug/plat e (-S9) : 10 , 20 . 40 , 8 0 ng/m l (+S9) : 1250 , 2500 , 500 0 jig/m l Resul t

Negativ e

Negativ e Note : ±S 9 = wit han dwithou t metaboli c activation . FA L180 0 1 . Acut e toxicit y (oral/dermal/inhalation) ; OPPT S 870.11.00 , 870.1200 , 870.130 0 Acut e ora l toxicity , acut e derma l toxicity , an dacut e inhalatio ntoxicit y studie s usin g S D rat s wer e conducte dwit hFA L180 0 containin g 5.25 % PDJ . Th e acut e ora l LDs o wa s >500 0 mg/k g bodyweigh t i nbot hmal e an dfemal e rats . Th e acut e derma l LDs o o f

FA L180 0 i nmal e an dfemal e rat s wa s >200 0 mg/k g bodyweight . Th e acut e inhalatio nLCs o o f FA L180 0 wa s >5. 0 mg/ Li nmal e an dfemal e rats . 2 . Ey e an dderma l irritation , an dski nsensitization ; OPPT S 870.2400 , 870.2500 , 870.260 0 Primar y ey e an dderma l irritatio nstudie s wer e conducte dusin g Japanes e whit e rabbits . I nth e ey e study , th e maximu mo f th e weighte dmea nscor e accordin g t oth e Drai/ e gradin g metho dwa s 52. 0 i nth e no neye-washe dgroup . Classificatio n

o f irritatio neffect s base do nthi s valu e an daccordin g t o th e Ka y an dCalandr a metho dreveale dtha t

th e degre e o f

irritatio no f

th e tes t substanc e wa s "severel y irritating. " However , i n bot hth e no n eye-washe dgrou p an dth e eye-washe d group , simila r

acut e symptom s wer e observe dafte r administration , bu t

wer e resolve db y da y 7 afte r

administration . I nvie w o f thes e results , i t

wa s conclude d tha t FA L180 0 produce s reversibl e intens e irritatio ni nth e eye s o f rabbit s unde r th e condition s o f

thi s study . N o irritatio nwa s observe di nth e skin . Aski nsensitizatio nstud y (Buehle r method ) wa s conducte dusin g Hartle y strai n guine apigs . N o ski nsensiti/atio nwa s observed. ) /) . Aggregat e Exposur e i . Die/an ' exposui'e . (Th e potentia l fo r non-occupational , dietary , an dnon dietar y exposur e t o Prohydrojasmo nb y th e genera l population , includin g infant s an dchildren , i s likel y throug hingestio no f treate dfruit. ) 1 . Food . [Dietar y exposur e t o Prohydrojasmo nshoul dno t b e o f concer ndu e t o th e lo w toxicit y show nacros s th e entir e toxicologica l profil e (se e above). ] ii . Drinkin g 'water . (Prohydrojasmo ndoe s no t pos e aris k

t o drinkin g water , a s agricultura l practic e prohibit s direc t applicatio no f

th e end-us e produc t

directl y t o water . Further , base do n th e environmenta l fat e studie s submitte dt o suppor t th e Experimenta l Us e Permit , Prohydrojasmo nrapidl y degrade s i nth e environment. | 2 . Nat'.-dittar v exposure . (Non-dietar y exposur e t o prohydrojasmo nwil l b e muc hmor e likel y throug hhandlin g b y formul ator s an dapplicators , bu t i nligh t o f th e subjec t

chemical' s toxicologica l profile , shoul db e o f littl e concern . Ther e ar e n o non-pesticida l use s o f

prohydrojasmon . Ther e ar e n o residential , indoor , schoo l o r cla y car e use s propose dfo r thi s product . Th e propose dus e patter ni s fo r agricultura l foo dcrop s (apples) . Therefore , ther e i s n o potentia l fo r non occupationa l exposur e t o th e genera l population. ) /•' . ("I'liuilativ e Effect s (Sectio n408(b)(2 ) o f

th e FFDC A require s that , whe nconsiderin g \vhethe r t o establis ha nexemptio nfro matolerance , th e Agenc y conside r availabl e informatio n concernin g th e cumulativ e effect s o f th e particula r

ingredient' s residue s an dothe r substance s tha t

hav e acommo nmechanis mo f toxicity . Thes e consideration s includ e th e possibl e cumulativ e effect s o f suc hresidue s o ninfant s an dchildren . Ther e i s th e possibilit y tha t

th e huma npopulatio nma y b e cumulativel y expose dt o othe r plan t hormones ; however , base do nth e ubiquitou s natur e o f thes e hormones , i t

i s unlikel y tha t detrimenta l effect s t o th e huma npopulatio nwil l occu r throug hthei r

use. )1 . U.S . population . [Wit hrespec t t o th e potentia l fo r

harmfu l effect s o f prohydrojasmo n i n th e U.S . population , th e toxicit y an dexposur e dat aar e sufficien t t o adequatel y addres s potentia l exposur e t o prohydrojasmon . Ther e i s reasonabl e certaint y tha t

n o har mwil l resul t

t o th e U.S . population , includin g infant s an d children , fro maggregat e exposur e t o residue s o f prohydrojasmo na s aresul t .o f preharves t

uses , a s toxicit y an dexposur e i s expecte dt o b e minimal . Thi s include s al l anticipate ddietar y exposure s an dal l othe r exposure s fo r

whic hther e i s reliabl e information . Thi s chemica l wil l b e applie da s aplan t growt hregulato r

t o apples. ] 2 , Infant' s an dchildren . |l. t i s believe dtha t

th e potentia l exposur e o f infant s an dchildre n t o residue s o f prohydrojasmo nthroug hit s us e t o enhanc e th e colo r o f re dappl e varietie s i s n o greate r tha ntha t

o f th e genera l population . Availabl e informatio ndoe s no t

sugges t tha t infant s an dchildre nar e mor e susceptibl e t o th e effect s o f prohydrojasmo n tha n ar e adults. | (.'•> . Effi'ci s u u I he'Immun e an dEndocrin e Syxu-m s [N o specifi c studie s hav e bee nconducte dwit hprohydrojasmo nt o determin e whethe r i t ma y hav e a neffec t

i nhuman s tha t

i s simila r

t o a neffec t

produce db y a naturally-occurrin g estroge n o r othe r endocrine-affectin g substance . However , i t i s no t likel y tha t

prohydrojasmo n woul dhav e estroge no r endocrin e effect s sinc e i t i s structurall y simila r

t o anaturally-occurrin g plan t hormone , i t

ha s demonstrate d lo w mammalia n toxicity , an dther e i s n o evidenc e tha t prohydrojasmo naffect s th e immun e system , function s i namanne r simila r t o an y know nhormone , o r tha t i t act s a s a n endocrin e disruptor. j .'/ . /'."v.'}///7 g Toleranc e [Ther e ar e n o U.S . tolerance s o r toleranc e exemption s fo r prohydrojasmon. ] / Internationa l Tolerance s \CodexMaximu mResidu e Level . N o maximu mresidu e level s (iMRLs ) hav e bee n establishe dfo r

prohydrojasmo nb y th e Code x Alimentariu s Commissio n (CODEX) . Th e Europea n Unio n(EU ) ha s assigne dadefaul t MR Lfo r

prohydrojasmo no f

0.0 1 mg/k g accordin g t o Articl e 18( 1 )(b ) Reg . 39672005 . Th e Japanes e Ministr y o f Agriculture , Farmin g an dFisherie s (JMAFF ) ha s assigne da n iVlR Lfo r

prohydrojasmo no f

0.0 5 pp mi n apple s an dgrapes. ]