Ma y 2 5 , 2012



### EPA REGISTRATION DIVI SI ON COMPANY NOTICE OF F1LING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER (7/1/2007) EPA Registration Division contact : [insert name and telephone nu mber with area code] INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In cases where the outline el ement 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, i.e . , "[insert company name!," with tbe information specific 

### to your action. TEMPLATE: [Bayer CropScienc e 

### I !Insert petition numbe r

' ! LP. \ !Ja - . , l1.T1.'liL'd .1 pe: - .uude p c t Hion 

### ([insert petition number]) lron1 I. Bayer CropScience

j , [P.O. Box 12014,2 T.W. Alexander Dri ve , Research Tri angle Park, NC 

### 27709] prnr,l.., Ji l . [HI "''ant to 'c - ctHHl· W {(!J ol'thc 

### h . : d1.'1al l · oud . Dru. 

### a11d · (_',,..,nh 'l l l .. \vt•f - lD( \ 1 

### _'ll S.C.3 - +6aldl.toamend - 4(J(l · RparliX Ilh)l'"l.thli...,hiH a •nk e11 " . I· t 

### r ..., 

## 'd''" ' "' IJ> rotbioconazol e , 2 - [2 - ( 1 - chlorocyclopropyl ) - 3 - (2 - chlorophenyl - 2 - hydroxypropyl] - 1 , 2 - d ihydro - 3 H - 1. 2 , 4 - triazole - 3 - thione and it desthio metabolitel n t I)J t1tl till.' r< '>\ o1 ptocc: - .: - .cd a gJ JLUitund l<'ll!!JliJJlt) 

### [bushberry crop subgroup 1 3 - 0 7 8] .11 

### [2.01 p;trh JWr million 

### 1ppn1J. [Iow growing berry crop subgroup 13 - 07H (except strawberry)] at 

### LO.lSl part JKI nu !ilnllt ppml. und 

### [cucurbit vegetab l es crop group 9] .,, [0.3] p.ut-- pet lll i lliun !ppn 1 I·P \ Jta, d \ :t ·,mined ih.ll t il ' l J ' l ll!llll ' ,cnl!,l!!• - . l dl.t ,,, II t I :.,u;,.l l'l .'tdlll g the l'kliiL'Iih -- 1 h'IIil Ill ' L ' ll n ll .!(ll - ) td )( 2l nl I·J)!)( \ . !a • '< \ L q :. l.f' \ h.J' - IJ,,r 

### i1dl, I.' \ <tlUc.Jll'd tlh ' lll !'1, IL"ll L ' ) ll !Itt· "libsnillcd data ;11 tin' Il l I l ' l nt v, h t ' i)IL'I ll1c d,H,: 

### 'uppu1 h 

### gran t mg. ol 

### the p .·tHJUn . 

### \ddi ti o md da t a ma) lK · lll'l.'dl.'d h,:iot\ ' I P ·\ tllk ' • 11) lilt' pt>tllinll

1 1 - 'lu!ll ll'

c 'tol. , oft ''" - 

### l ln plants. Lhe metabol i sm of prothioconazole is adequately und erstood for purposes of establishing th ese proposed to l erances. Prothioconazole was extensively metabolized in plants with the major resid ue found in all crops (wheat, peanut s and sugar beets) being JAU647 6-desthio with sma ller amounts of v arious i o me rs of JAU647 6- hydroxy- desthio. and their conjugates also being found. Triazolylalanine. triazolylhydroxyprop i onic acid. and triazolylacetic aci d , metabolite s 1 1 1 1 1 1 1 1 1 1 11 1 1 1 111111111111111111111 M - 431155 - 0 1

- 12

com!l'I{)J1 LO the tri azole - derivative clas: - . of fungicides. were also found. Based on the abovl! data the residue s of concern in planh are prothiocona i . ' ole and its metabolite Jt\U6476 - desrhio. 

### The risk a'sessment for 

### the common metabolites ari<.;ing 

### from the triazol c - dcri\ ativc fungicide i bein g addr e . . . . ..,e d h\ t



### - he US Triazole Task Force. [n large anirnal . . . . . the nature of re idue - ; is abo adequately under....tood for purposes of establishing the pruposcd tolerances. The residueof concem in edible tissues and milk arc prothioconazolc. i r s metabolites JAU647 o -desthio, JAU6476 - 4 -hydroxy. and their conjug a t e s that can be converted to these thr ee compounds by acid h ydro l ysis. ) t,, ·, "•' 1u 1 ,, (The analy 1ical method for determining residues of concem in planb xtracb re - ,idue' - > of prothioconazole and JAt i 6476 - de - ;thi o and com erb the prothioconazole to JAU6476 - desthio and JAU6476 - sulfonic acid. Following the addition of internal standards, the sam ple extracts are analyzed by LC/MS/MS. Radiovalidation an d ind ependent laboratory validation have shown that th e method adequately quantifies prothioconazole re idues in treated commodities. The validated LOQ for total prothioconazole - derived rc<>idues was 0.02 ppm in blueben - y fruit, cranbeJTy fruit. cucu mber. melon . and - .qua'>h. The validated LOQ'> were 0.01 ppm for IH - 1 ,2.4 - triazole and the triazole conjugatefor blueberry fruit. cranbeJ Ty fruit. cucumber. melon. and '>quash. The analy tical method for ana[y..;is of large animalti! - .'>Ues indude - . extraction of the residues of concern, followed hy addition of an internal standard to the extract. The extract is then hydrolyzed to release conjugates. partitioned and analyzed by LC/MS/MS as prothioconazole, JAU647 6 - desthio and J AU6476 - 4- hydroxy. rhe method for analysis of milk eliminated the initial extract i on \tep in the tissue method . 

### I

lu " 11111dj "' n 'idrr( ' 

### I Resid u e trials were conducted in the various required regions across the United States and Canada in accordance with the EPA and PMRA guidances for crop field trials (OPPTS 860.1500: DACO 7.4.1: DACO 7.4.2) to supp011 tl1e tolerances requested nhove including the following: Bushben·y (Crop Subgroup l3 - 07 B ): A total of I I field trial s were conducted on blueberry as a representative of Bushherry (Crop Subgroup 13 - 07B) in the USA a nd Canada. Cranberry : A total of 6 field trials were conducted in the USA and Canada on cranberry a' -> a repre cntative of the Low Growing BetTy Subgroup except Strawheny (Crop Subgroup 13 - 07H). C'ucurbit Vegetables: A total of 24 fidd trials (8 trial each on cucumb r. muskmelon. a nd squash) were cond ucLed in the USA and Canada.

, • 't o • • , • 

### I Prothiocona.wle exhibits \ ·ery low acute oral. dermal and inhalation toxicity . The acute oral LD50 

### ror prothioconazolc in rats was >6200 mg/kg/day while the dermal LD50 was >2000 mg/kg/day and the four- hour rat inhalat.ion LC50 >4990 mglm3 • Prothioconazole was not iJTitating to the eye or skin of rabbits and di d nol t:ause skin sensitization in guinea pigs. )

_ ( ; ( 1111 ' >llt' (Prothioconazole is not mutagenic. Slightly positive and3

J ' - ., equivoc a l re: - 11on"c een in 

### in vitro C\ .10£encti(.: and UDS assavs were neuativc in 

### in 1·ivo tc - ..t ! - . . j /11 1 / 11·11• •" 1 ,, \ llmmunotoxidty potential was evaluated i.ls part of a

- ..ubchronic lt>xicity study in rats. Determination of cell countin the spleen and perfomwnce 1)f the plaque - forming as..;ay '>ho v: , ed no e\ · idencc of treatment - related immu notO

. \tCity at do! - >eup to 500 mg/kg.lday (the highest do"e tested) for 31 days. The rc ... uil'i of thl ' ..;tudy. in addition to additional '>tudic - .. conducted u..;ing mice and dogs. suppon that prothiocona7.ole is not considered to 

### he immunotoxic.l

, • • ,.. • ' I< , •• ,, '', ' • , IProthioconaJ .olc is not considered a primary rcprodudive toxicant in a two - Generation rat reproduction ..;tudy . The NOAE L ror parental to x i(.;ity as well as rhe NOAEL for reproductive and neonatal effects is 95.6 m kg bw/da y In the rat oral developmental toxi :ity . - ,tudy the fetal NOAEL was 500 mgfkg ln . vid.t) and the maternal NOAEL V>a:-. 80 mg/kg hvdday . A doe le\CI 

# or 1000 mg/kg hVIJ

day aJmini - ..tered to the rut by the dermal route doenot elicit developmental toxicity. In the rabbit, prot hioconazole doe" not produce developmental toxicity at dose levels exceeding the maximum tolerated dose. Thu: - .. prothioconazole is not tcratogeni<.: in l'ithcr the rat or rabhil.] .;, ' •· , j{}O - day feeding studte: - . c o ndu tcd in rat: - . mic e . and dog - ; : - ho" ·cd the li\Lr and/or kidney to he the target organ - .. 

### In the: - ,e ... ubchronic studies NOAEb were established at I 00 mg/kglday for the rat and 

### 25 mg/kg/day for the mou: - .c and dog. 

### I

" ( n . , 

### I Prothioconazole is not ca rcinogenic in either th e rat o r the mouse even at dose levels in the rat exceeding the maximum tolerated dose. The liver ami kidney arc target organs 

## or prothio<.:onazole for non - neoplasti<.: toxicity in the rat, mouse and do 

# - g. The lov.cst NOAEL established on the ba"is of Jon!! - term toxicit v 

# - 'tudies is 5 mg!kg hw/day in the rat chronic toxicity/carcinogent<:ity stud y and the dog 5 2- week toxicity study . 

### I

· \ u . ,.,.,I '· 'il',ul, , n: [Metahol ism and pharmacokinet i<. : studie in the rat demonstrah.' that prothioconazole is rapidly ahsorheu. metaboli7cd and eliminated. The primary tm:taholit" induued JAU647 6-desthio. a - . 

### \ .' - 'CII us S - and 0 - glucurnnide of p n lthi ocona;o k

. • J



## -. . : '1 , , ; . •I ,. ' • , ).., [The major metaholi t e of prothioconazole in the rat. plants and large animal' i - . JAU6 - t76 - de thio. The refore. a comprehensive evaluation of the mammalian toxicity of J AU6476 - desthio has been performe d . The acute oral. dermal. and inhalation toxicity of JAU6476 - de..;thio in the rat is low ( LD50 valw.:': 2806/1506mg/kg 1 male/female!. >5000mg!kg. 4 - hour LC5 0 : >5077mg /m ' . rc pectivcly ). It is non - in·itating to kin and only very - .lightl y irritating. t0 eyes and has no cutaneous sensitizing. potential by topical application. The short and l o n g - tenn ornl toxicity of 

### J AU6 4 7 6 - de thio has been investigated by4



# -

dietary admini tration in the rat. mouse and dog. The common target organ in a ll 3

- .pecies is the l i vcr. Secondarv

. effects on the th

## .

vroi d m the rat a nd do ! 

### .

: 

### . ! 

### . were a s: - . o c iated ' N ith 

### increased h epati c enz yme induction. In the long term 

### studies, 51 weeks in 

### the rat an d 30 wech in the dog. the NOAEL f or the rat and th e do g

# were I. I and I 0.1 mVk2



### ... bw/day , respectiv e ! y. J A U6 4 7 6 - desthi o is not carc ino ge nic in either the ra t or the mouse. The NOAEL se l ected for human risk a;.;sessment i s 1 . 1 mg/kg bw/clay established in the c ombined chronic toxicity and c arcin ogenicity s t ud y in the rat. JAU 6-+ 7 6 - deslhi< ) was negati ve for mutagenicity and genotoxicity in all in ritro a nd in r im studies both ' - "'ith and " ithout metabolic activation. In a two - generation reproduction s tudy the maternal NOAEL was 2.7 mg/kg bw/day and the NOAEL for rep r

oductive and neon ata l e ffect s I 0. 0 mg/kg bw/day. Th e main targets at the highest dose were dystocia (probably - >econdary t o hepatic t ox i ci t y ) , decreased pup viabi lity. gro wth retard at ion and low incidence o f cleft pal ate s . In the de v e l op m ental toxicit y 'tudies deft palate\ were : - .een in the rat and rabbit at the hi g h est doe leveb and \

upemumerary rihin the rat a t lower dose lc\ 'e ls. Th e oral N OAEL i - . l mg/kg bw/day in the rat and 2 mglkg/day in the rabbit. A developmental ncmotoxicity "tudy tDNT) in rats wa: - . conducted with JAU6476 - desthio athe a nticipated dietary exposu r e is mainl y to JAU647 6 -desthio and not the parent. No evidence o f neurotoxicity was s een in this study. i ncluding no c o mpound - re lat ed effects involving neurobehavioral tests and neuropat h ology . C o m pou nd -re l ated effects "ere limited to overt toxicity and developm e ntal effects which were con"istent with effcch seen in other developmentaltoxicitstudie s . The overall NOAEL was 3.6 mg./kg b w/ day.j

u ' ' '' " • t ,, , , I• .,, '·' [The toxicology database for prothioconazole i s c urre nt a nd complete. Studie - ., in thi" databa: - e include eva luation of the potential e ffects on carcinogeni c, r eproJuct ion and de , · elopment effects i ncluding an evaluati on of the pathology of th e end o c rin e Grg a n s following s hor t - or long

- term exposure. Prothioconazolc i

! - 1 consi de red not to have primary cndo<. : rin e cf f ect'i. l

i i>t c un , ,L (An aggreg at e ri sk assc), s m ent was conducted f or all existing re g i stere d u: - . e - . on barley: dried beans and peas (Crop Group 6C): canola; peanut s; wheat: triticale: soybeans: 'ugar beets: cereal grain c rop group 15 and 16 (except s o rghum) swe et corn: ri ce: al fall'a: potato a nd this proposed petition requesting to l e rance on cucu rbits (Crop (]roup ). blue berry (Crop Group 1 3 B ). and cranberr y (Crop Group 13H) . A previou s Tier 2 d i e tary risk a

sse s sment w a

: - . conducted 

### by EPA (PC Code 11396 I) on Decemb er h_ 20 I 0 . Resid u es for th e additional crop groups were bas e d on highest average l' ield trial ( H AFT) for acut e assessment and the average r e - . idue for chronic assessment.5



# .

The acute toxicity endpoin t U! - .ed in the acute assessment was the NOAEL of 2 . 0 mg/kg/day from the prothioconazole - desthio rabbit developmentaltoxi<:ity study as dc crihed 

### in the Agency" HED ri sk assessment memorandum on prothioconai'.ole dated Januar y 5. 2009. No acute endpoint 'A- as identified for the general U.S. population: Female! - .. 1 3 -9 ye ars of age. \'vas the only population ' - Ubgroup to be included in the aL · ut e <1' - '! -- .Cssment. Application of a J()Ox uncertainty factor re - ..ults in an acute reference close (aRID) of

0. 02 m g/kg/day . The chro ni c reference dose (cRfD) ofO.OJ l mglkg/day results l'rom applying a I OOx unc e 1 t a im y factor to the NOAEL of 1.1 mg/k g/day from th e rat chronic\oncogenicity prothioconal'ol c - desthi o toxicity 'iludy . The acute and chronic dietary assessment<> for combined food and water exposure show 25 < -r utili?ation of the aRID by fe male! - . 1 3 - 49 years and 63<' utilization of th e cRfD by the mo s t sensitive subgroup. all infants. Rc! - .ults from the dietary exposure assessm e nts <. kmPilStra t c a reasonable certainty th at no hann t o the overall U . S. population or any populat iun ' - >Ubgroup will result from the U! - .C or prothioc011 11 0 l e 011 the above crop s .}

'"'' (An acute. Tier 2 dietar y (rood only) ri - ;k as<.;essmcnt was conducted. For the population subgro

up females 13 -49 ye ars o ld. the acute a na lysis indicates an e - xposure of 3.75% of the aRID a t the 95 1 h p ercenti l e . R esults from 

### a c h ronic, Tier 2 dietary (food on l y) risk assessment show that the most highl y exposed popu l ation 'iubgroup i ! - . children I to 

### 2 ye ars w ith an exposure equal to 9.7 c /c of the cRtD followed by aJI infants at 

### 3.9Clc. Chronic exposure to the overall U . S. population i - . 3.2 " k of the c RtD.]

' fJ ,,. ,, ,, 

### l'

i • '' !No monitoring data are availab l e for residues of prothioconazole in drinking w ater. and EPA has established no health adv i sory levels or maximum contami nant leveb for re s iducof prot.hioconazole in drinking wate r. In order to addres - ; drinking water. water was included in the dietary ana lv sis for food. DEEM anal ysc" v. - ere performed using the upper hound estimates for the cranberry crop scenario: the E D WC for the acute and chronic a <.,e! - . ment is 94 pph. For the population subgroup females 13 -49 year- . old. the acute analysiresults in an exposure of 21 ( fl of the aRID. R e: -- .ults from a chronic. T i er 

### 2 dietary risk u: -, : - - . essrnent indicate that the most highly exposed population subgroup w as all infants with an exposure equal to 59% of t h e cRfD. Chronic exposure to lhe overall U.S. population i ! - . 18% of the cRfD.}

\ , , '"! , [Prothioconazole j.., not reg i .. . tere d for residential uses nor arc any registrations pending for 'uch use . 

### I [Prmhiocouazole i a member of the conazole family of fungicides. The cumulative effect! - . of the primary common metabolite! - . are being addressed by the US Triaznlc Task Force. 

### I

l \ , ,'i' tf, .,,,, (In the Agency'.., HED risk a..;sc<..smcnt memorandum on6

prothioconaLOie dated October 13. 2006. it is stated that quantification of acute risk to the general population including infant.;; and children i no t required. Based on the conservative 

### exposure a sumptiont'i described above and 

### on the completeness of the toxicity data, it can be concluded that total food and drinking water exposure to prothioconazolc irom all proposed uses wi ll utilize 25% of the acute RfD for females 1 3 - 41.) years old ami 21.2% of the chronic RtDs for the overall U . S . population. EPA genera ll y has no concerns for exposures below 10 0 % . of r.he 

### RtD. because th e RID represents the level at or helow which daily aggregate exposure over a lifetime will not pose appreciable risb to hum an health.j 2 . /nftlllh tlltl, ,,, tJ'• '' [In the Agency"s HED ri sk assessment memorandum on prothioconazole d;.tled Janua r y 5. 2009, it is stated: ·'There are adequate data in the prothioconazole ( incluu ing metahoiites) database to characterize the potential for prenatal or post - natal risb. to infants and chi ld ren: tw o - g e neration reprodu c ti on studies in rats; developmental qudies in rats and rabbits; and a developmental n e urotoxicity study in rat s . The effects seen in these studies suggest that offspring are more susceptible: ' - '' - ' ' - ot' f pring effectwere seen at le\ ·els below the LOAELs for matemal toxicity and. in general. were of compara ble or greater severity compared to the effects observed in adults . However. the point of departure for the most sensitive of these stud ies (the rabbit developmental toxi ity) is lower than that of the other studies (2 mglkg/day), and is based on effects observed in the fetus. not the parent. Therefore, the offspring are con s i d e red to be p rotected and there is no need to retain the I OX FQ PA fac tor. and it is reduced to I X." EPA also s tat ed ·'No ac ute endpoint was idenrificcl for the gener a l U.S. population. Female s . 13 - 49 years 

## or age. wathe on I y population subgroup included in the acute assessment.·· In addition to the adequacy of the toxicity databas e , there are also no uncertainties with respect lo the exposure database. Both the dietary food and water exposure assessments are conservative in nature . Additionally, there is no potential for residenti a l exposure. 

### In Bayer"s dmmic exposure assessment. th e 

### most highly exposed population s ubgrou p . all infant s. uti l i zecl63 Cfr or the chronic RfD. EPA genera lly h a s no concerns for exposures helnw I OO C

1 ' of the RfD. hecause the RfD represents the level at or below which daily aggregate exposure over a lifetime \),.'ill not p ose appreciable risks to human health.! hlf< n;,,•rr•Jt/1: I oft r(l/, t ·, [lnt emational tolerances/MRLs for prothioconazole have been esta b l i shed f

or vari o u s crops. Hov ,

: e ver. none have been establi s h ed for bushbetTi e s. low g rowing berries or cucur bit vegctahles.J