# Proposed Registration Decision for the New Active Ingredient Oxathiapiprolin

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### SUMMARY This document a nn o un ces that the Env ironmental Protection Age n cy (EPA) has completed its eva lu ation of the dat a/infonnation submitted to s upport the propo sed new fungicide oxathiapiprolin (CAS# I 0033 1 8-67

- 9). The Age ncy h as determ in ed th a t it m eets the regu latory and safe t y s ta nd a rd s under the f ede ral In se cticide. Fungicide an d Rodenticide Ac t ( FIFRA ) and is p ropos ing to register a wide variet y of uses for this chem ical. EPA has adeq uate in forma ti o n and data to s upport thi s proposal a nd no add i tional data a rc needed for reg i s tration. Oxathiapipro l in is a fungic id e for co n trol of dov.rn y mildew (caused b y Pythium spp) and l a t

e bl ig ht (ca u sed by Ph yt op hthora s pp.) di s eases o n food , o rnamental c rop s a nd golf course tur f. Five p rod u cts a re propo se d to be unconditionall y registered und er Section 3(c)(S) of FIFRA
. The 

### E. l. DuPo nt De Nemou r s and Co mpan y proposes a technical and two end-use products n a med ·'DuPont Zorvcc T ec hni ca l ", ··DuPo n t Zorvec Eni cad e fungicide"' , and " DuPont Zo rvec Ep ica ltrin Fun g icid e"'. Sy n genta Cro p Pr o t

ec ti on. LLC proposes two end-use products: ' ·Oxathiapiprolin FH G O D ' ' and "O xathiapiprolin FHG 

# sc··, vvhic h have additional uses fo r oxath ia piprolin. E. 

### I. DuPont De Ne m o urs and Co mpan y propo ses the fo ll ow in g o utdoor food crop s: Brass ica, Head a nd Stem, Crop S ub g ro up 

### SA; Bulb Oni o n C rop S ub g roup 3-07A; C ucurbit Vegetabl es, Crop Gro up 9: Fruitin g Vegetabl es, Crop Group 8-10 ; Grapes ( import o nl y): Green O nion. Crop Subgroup 3-078; Leaf y Gr eens, C rop S ubgroup 4A ; Peas, edib le-podded: Peas , s ucculen t , she ll ed; Gin se n g ro ot; T ub erous a nd Co rm Ve geta ble s, S ubgroup I C; a nd tobacco. The pr o po se d maximum app li ca ti on rates of oxathiapiprolin on crops ranges between 0.1245 l b. a.i ./ A/year for m ost fo liar app li cations. and 0.5006 lb. a.i ./ Nyca r for so il a pplic ations. Th e label s a llow 2 to 5 re treatm e nt s ( 1 2 dre n c h treatm e nt s for o rnam e nt a l plants) and rctreatm e nt int erva ls be tween 3 to 14 days . Th e p re-ha rves t interval ran ges from 0 to 14 days . Synge nta proposes th e fo ll ow in g non-f oo d u ses: a w id e vari ety of ornamen t a l plant s g rown in gree nh o u ses. s h ade h ouses . lath house s. hoop h o u ses . nur se ries. co mm ercia l la n dscapes; and go l f course turfto include g reens , t ees, and fai rways. Th e proposed oxathiapiprolin label direc tions allow product applications to either food crop fo l iage or to th e soil, but not a comb in ed app li cation
. Pr o duct app li cations a r e proposed by g round and ai r s prays. c hemi gati o n , so il d r ench / s pray. and drip irri gation
. The proposed e nd-us e product label directions are intended for u se by professional ap plic a tors. Th e re is a lab e l restriction agains t u se fo r hom e plantings. The propose d oxathi ap ipro lin labe ls were assesse d a nd found to be app ropr iate for u ses in g ree nhou ses on orna m e n tal plants , tomato es, cuc umber s, s ummer s quash, be ll pepper s, and n o nb e ll peppers. A ll other foo d u ses on the l abe ls wi ll have a rest ri ction s tatem e nt again s t app li cation s in a g reenh o u se beca u se th ey were n o t requ es ted and thu s n o t assessed. Th e c h e mical was gra nte d redu ced ri sk s tatu s b y the Age n cy's R ed uced Ri sk Commi ttee as part of th e registrant s " requ es t for that determination o f oxathiapipro lin data for all food and non-food use s . T he toxico lo gy database is co n sidered complete

. Du e to the limited tox icity observed fro m th e tox icologica l datab ase, E PA determin e d that qualitativ e r isk assess m e nt s were the
2appropriate wa y to characterize this ch e mical. For human he alth , E PA c o nducted a qualit a ti v e ri s k a ssess ment , in w hi c h t o xi co l og ica l e ndp o int s a nd p o int s of d e p a rture ( POD ) w e re n o t ev ident f o r oxath iap ipr olin. Numeric to le ranc es are not needed but will be es tabli s hed onl y to s upp o rt intem a ti o n a l h a nn o ni zation p urp oses. O x athiapiprolin is a br oad- s p e ctrum fun g icid e with pre v ent a ti v e , res idual , sys temi c . e radic a ti v e. a n d anti s p o rul a nt prop e rti es f o r f o liar a nd s oil-b o m e fun ga l di sea ses . 

### It pr ov id es a differ e nt mod e o f action than other fun g icide s and thu s could minimi z e d is ea s e re s is tance. A s proposed , it would b e a ppli e d in a sc he dul e d prot ec tiv e prog ram a nd u se d in an a ppli cati o n ro t a ti o n pr og ram w ith pr o duct s w ith a di ff erent mod e of a c ti o n. 

### BACKGRO UND EPA rece iv e d DuPon t's thre e product a pplic a t ions and Syn ge nta 's two product app li cation s on 1 2/ 3 / 2 0 1 3
. Th e DuP o nt a ppli c ati o n s we r e a lso s ubmitte d f o r s imulta n eo u s r ev iew t o the P es t Ma nag e m e nt R eg ulato ry A g e n cy ( PMRA ) o f C anada and oth e r c o untrie s . Sy ngenta 's n o n-food o m a mental plant applic a tion s w e re onl y s ubmitte d t o EPA b e cau se r eg i s tration f o r the s e u ses i s n o t b e in g r e qu es te d f o r u se in Ca nad a. E PA and PMRA co mbin e d th e ir r eso urces and co ndu c t e d a g lo bal j o int re v iew of ox athi a piprolin foo d u ses w ith p articip a ti o n fro m A u s tra lia , Me xico a nd Japa n, and r eg ulato r y ob se r v er s from South K o re a , C hina , and the Philippin es . Eac h countr y c o nducte d primar y o r se c o ndar y r ev iew f o r th e 4 11 s tudi es s ubmitte d. Hum an health a nd e co log ica l ri s k a ssess me nt s w e r e dev el o p e d b y E PA and PMRA individua ll y. DuP o nt p e tition ed EP A under th e Fede ral Foo d , Dru g a nd Cos m e ti c A ct ( FFD C A ) to establi s h to le ranc es for th e food crops li s te d ab o v e. At thi s tim e, there a re n o es tabli s he d C o d ex m ax imum res idue limit s ( MRL s) f o r oxathi a pipr o lin
. 

### EVALUATION OF RISK TO H UMAN H EA LTH AND THE ENVIRONMENT In evalu a tin g a pes ti cide reg i s tra ti o n app li cat io n , th e E PA assesses a , ..,ide vari e t y of pes ti c ide s p ec ifi c infonn a ti o n in c ludin g w he re a nd h ow th e p es ti c ide wo uld b e u se d . e nvironmental fate (i.e
.. w h a t h a pp e n s to the pes ti c ide o n ce ir s ap pli e d ). a nd t ox ic ity s tu d ies (i.e
.. effects o n hum ans a n d o th e r no n- ta r get o r ga ni sms) t o d e t er

min e th e li ke lih ood of a d ve rse ef f ec t s (i.e
. . ri s k ) fro m ex po s ures as so c ia t e d with th e pr o p ose d u s e o f th e pro duct. Ri s k assess m e nt s are d eve l o p e d to eva l ua t e th e env iro nm en tal fate of the compou n d as we ll as h o w it m ig ht affect a wi d e ra n ge of n on- t a r ge t o rga ni s m s in c ludin g hum a n s a nd t e rr es tri a l a nd a qu a tic w ildlif e ( plant s a nd anim a l s)
. On th e b as is o f th es e assess m e nt s . E PA eval u a t es a nd a ppr oves lan g u age fo r e ach p es ticid e la b e l t o ens u re the direc ti o n s fo r u se a nd sare t y m eas ures a r e a ppr op riate t o mi t igate a ny ri s k s of co nc e rn. In thi s way. th e p es ti c ide ' s l a b e l he lp s to co mmuni cate esse ntial limitati o n s and miti gati o n s th a t a re n ecessary for p ub li c safety. It is a F IF RA v i o lat io n to use a pes ti c ide in a way th a t is inc o n s is t e nt w ith th e la b e l. 

### Assessment of Ri s k to Human Health

3The toxicology database for oxath iapip rolin is considered comp lete for the purpose of risk assessment. In the ora l and dermal guide lin e toxicity studies, including subchronic. chronic, n eurotox icity, and immunotoxicity studies, no treatment rela t ed effects were seen at doses up to the limit dose. No treatm ent r e lated effects were observed in maternal or fetal animals in rat o r rabbit developmental toxicity studies. Treatment related effects were observed in offspring animals in rat r eprod uction s tudi es. Howeve r , these effec ts were only observed a t do ses above the limit dose. Such high doses are n ot relevant for human health risk because human exposure at this level is not anticipated in conjunct ion w ith the use directions on the proposed product labels. There was no evidence of carcinoge ni c i ty in can cer studies with rats or mice. Oxathiapiprolin is classified as ' ·n ot likel y to be ca rci no ge nic to human s.'' The re is n o mutagenic concern for oxathiapiprolin. including its metabolites. An inhalation toxicity study was not submitted. However, in consideration of all other available data and through a weight of ev id ence (WOE) approach. E PA co nclud e d that the inh alation st ud y is not r equ ired for oxathiapiprolin. B ase d on the lack of toxicity for oxathiapiprolin across th e database. the inh alat ion toxicity study has therefore been waived. Due to the lack of toxicity observed in the oxathiapiprolin da tabase , toxicological end point s and POD were not evident in the data for oxa thiapiprolin. Therefore, the norm a l quantitative ri sk assessment approach which uses e ndp oints is not needed and a qualitative human health risk assessment has been conducted to evaluate the proposed uses. Thi s includ es assess ment of dietary, residential. and occ up ational (han dl er and post-application) risk estimates. In ac ute toxicity stud ie s, ex po su r e to oxathiapipro lin resulted in the lowes t toxicity catego ry via the oral. dermal. and inhalat io n routes of exposure (Tox icity Category IV). Oxathiap ipr oli n is not a dermal or eye irritant, or a sk in sens iti zer. Oxathiapiprolin is n o t a dermal or eye irritant, o r a ski n se n s itizer. Based o n th e acu t e toxicity categories of the technical active in gredient the ReEntry Interval (REI) would be 

### 12 hours based on the Worker Protection Standard. However, DuPont proposed a 4 hour REI w hich is the lowes t RE I allowed on any lab e l. DuPont reque s ted the 4 hour REI based on satisfying the criteria in PR Notice 95-3 which are: (I) the acute toxicity ca t egories are III and IV for acute dermal, inhalation , primary sk in irritation , and primary eye irrit at ion ; (2) it is not a dermal se n sitizer; (3) it is not a c h o lin es t erase inhibito r: 4) there are no known reproductive. developmental , carcinogenic, or neurotoxic effects; and 5) there is n o adve r se incident inf o rmation ( illn ess or injury repo rt s) re late d t o post-application exposures. As stated below in the " Pr oposed Regulatory Decision. the Agency has evaluated the proposed REI reduction and dete1mined that the active in gred ient meets the toxicity criteria for red u c in g th e REI to 4 hours. The Per sonal Protective Equipment ( PPE ) s tatements on the proposed labels require handlers to wear baseline clothing (i.e., long sleeved shirt , long pants. shoes plus socks). The re sidue chemistry database is considered to be comp l ete. including adequate ana lyti cal m et hod s; m e tab o li s m in target c rop s, r otat ion a l c rop s. and li vestock; storage stabi lity; r es idues from field trials: and residues in proce s sed commod ities. All residue study results a re supported



### 4by adequate sto rag e s tab ilit y data. The field trial s tudi es were conducted u s ing th e proposed anal y tical e n forcemen t method. 

### Assess ment o f Ri s ks to th e E nv i ro nm e nt E nvi ron m e nta l Fa te Oxathiapiprolin is cha r acte ri zed by a re lati ve ly low wate r so lubility with low potential for vo latili zatio n fro m dry / wet and water s urface s. The octan ol/ water partiti o n coefficient s u gg ests that the c he mical ha s the p ote ntial to bio- co ncentra te in aq u atic o rganism s s uch as fish. Oxathiapiprolin is not expected to be affe cted by hydrol ys i s, aqueous ph o toly s is, and ph o to lysis in so il and anaerobic so il metabolism. The chemical is expected to be relatively p e rs isten t in the so il a nd w ate r se diment sys tems. In these so il and water sed iment sys tem s, b i o -tran s formati on/b iodegradation a r e th e major processes that are expected to affect th e fate of oxath iapiprolin. 

### Eco log ic a l E f fects Because of it s low sol ubilit y. oxathi api pro lin did not demonstrate acute or chronic effects of concern to fres hwater and estuarine / marine fish. Chronic Ri sk Quoti e nt s 

### (RQ) to fre s hwater sediment-d we lling invertebrates were es timated to be 2.72 w hi c h s li ghtly excee d ed the Level of Concern ( LO C) of 1.0 w he n ca lculated from se diment-based toxic ity end point s . Howeve r. th e chronic LOC was not excee d e d for any propo sed u se when th e RQ s were estimated u s in g pore water and water column based t ox icity e ndpoint s. To furth e r charac terize th ese findings , it is noted that se parate s piked-water a nd s piked- se diment sys tem toxicity s tudies y ie ld e d sediment and pore water-based tox icity endpo int s . T he endpo int s f ro m the sp iked sediment sys tem arc app r ox im ate ly an order of magnitude less than th ose determined from th e s pik ed water sys tem. Althou g h no s tud y i s availab le to chara c t e ri ze th e toxicity to se diment d we lling estuarine / marine in ve rt eb rate s, the current suite o f data for fre s hw a ter in ve rtebrates indic ate that estuari n e/ marine organisms are not di s proportionately m o r e se n s itive th a n fre s hwater organism s . Long e r term fres hwater se diment and fre s hwater water column toxi c ity s tudie s (2 8 day), as opposed to the guideline subchronic 

### I 0 -day tox icit y s tudies were s ubmitte d for freshwater in ve rtebrates. B eca us e the data indicate an expected s imilar level of ri sk to estuarine / marin e se dim e nt dwe lli n g organ is m s , no fu rth er s tudies characte ri z in g the toxicity to fr es hwate r or estuarine/ m arine sedime nt dwelling in ve r tebrates a r e needed as th ey are d e t e rmined to ha ve little overall added v alue t o th e current ri sk picture. T he r e we re no L O C exceedan ces oflis ted and n o n-li s ted spec ie s of aquatic plant s for the proposed use s of oxathiapiprolin. No acute and c hr o nic av ian and mamm a l LOCs a r e excee d ed, thu s , risk to bird s (an d their surrogate s) a nd mammal s are not exp ec t e d. De s pite th e e nvironme ntal fate data indi cating that oxathi a piprolin has the potential to bi o - co ncentra t e in aquatic organis m s s uch as fi sh , th e re wa s no acute or chronic risk above the LOC indicated for birds and mamm a ls con s umin g oxathiapipro lin- con taining aquatic taxa. Thi s is due primaril y t o oxathiapiprolin' s low acute and chronic toxicity to bi rds and mammal s . No ri sks above the LO C to terres trial plants are ex pected. The hi g hest app li cat ion rates te s te d on plant s. which was mo r e than twice th e hi g hes t prop osed app licati o n rate f o r all u ses of oxathiapiprolin , did n o t e licit a toxicity e ndpoint a t o r above the 25% tr igger level. The no- adve rs e
5ef fect co nc e ntration (NOAEC) also exceeded th e maximum application rate , reinforcing the conclusion of no ri s k exp ected for both listed and non-listed species of terre s trial plants. The res ult s of the Tier l risk a ssessm e nt to adult honeyb ees via direct contact and oral ex po s ure res ulting from foliar and so il applications, respec ti ve ly . indicate a ll RQ s fall below the terrestri a l in ve rteb rate ac ute LOC o f 0.4. A Ti e r II se mi-fi e ld be e s tud y was co ndu c ted which exam in es e ffect s from the larvae stage through pupation. to adults in an outdoor flight cage where bees are ex po sed to oxathi ap iprolin-tr eat ed blooming plant s. Thi s study indicates that while th e re were reductions in s urvival at Day s 12 and 1 3 afte r app li cation. as well as re ducti o ns in flight inten s it y o n the day of application. the bees recove r ed from th ese e ffect s durin g th e co urse of the 25 day s tud y. This is indicated when the e ntire study interval was cons id ered, all response variabl es re lated to colony hea lth. surv i vaL and foraging behavior were s imil ar t o controls. Bas ed on the r es ult s of th e T ier I hone y bee assessment which indi cated no LOC exceedances (i. e . acu t e contact a nd o ra l risk to adult hon ey bee s)
. and Tier 

### lJ semi-field s tud y which indicated hon ey bee co loni es s howed reco ve r y in multiple r es pon se variables, the pr o posed use s of oxathiap iprolin are not ex pecte d to s ignificantly impac t hon ey bees at th e colony leve l. Therefore, at this tim e, no a dditi o nal bee s tudi es are r e qu es te d. The eco log ica l risk assessment de t e rmin ed that for the following prop ose d u s e s. bras s ica vegetab les , bulb vegetab les, leafy veg e table s, peas , tobacco and turf , th e re w e re no acute or chron ic LOC exceedances of any taxa assessed a nd th a t a .. n o effect finding
.. can be m ade for li s ted s peci es. For all other propo se d us es th at include cucu rbit vegetables, fruiting vegetables, gin se ng , tuberou s vegetab le s. a nd o rn a m e nt a l s, the re was at l eas t one sce nar io assessed for w hich ther e was a n exceedance o f LO C ( RQ s ran ge from 1. 01 to 2.72) and the taxa of co ncern w e re fre s hw ate r se dim e nt d we llin g inv er teb rates ex p osed to oxa thi ap ipro lin on a c hroni c basis. It is noted that for the tuberous vegetab le u se scenarios that were assessed, the high es t RQ es tim a t e d was 1.0 I , negli g ibly above th e chronic LOC of I. For th e fruiting vege tabl es u se sce nario s . the hi g he s t RQ es tim a t ed was 2
. 72, marg inall y above the chronic LOC of 1
. 

### BENEFITS Oxathiapiprolin was granted r educed ri s k status for a ll th e prop ose d f oo d and non-food u ses . It is a broad-spectrum fungicide with preventat i ve, residual, sys temi c, e radi c ati ve, and a ntisporulant prop e rties fo r fo li ar and s oil-born e fun g al di s eases. Oxathiapiprolin appears to exhibit a uniqu e mode of action. It s unique mod e of act io n s u gges ts that it may play a role in resistance mana ge ment. 

### It can be u se d as part of an integ rated disea se control pr og ram with fungicid es of ot her modes of acti o n th a t can be part of a re s is tan ce m anage m e nt s tra t egy for the proposed crops . Re s is tanc e m a na ge ment reco mmendation s o n the agricul tural labe ls includ e th e limitation of no more than two seq u e ntial ap plic a ti o n s a nd u se of effective c hemi ca l a lte rnati ves in ro tation pro gra m s . Utilizati o n of integrated p es t man age me nt pr og ram s is also e ncourage d o n the propo se d l abe ling. It is intende d for u se as a fungicide for prote c tion of crops again s t diff1 c ult t o co ntro l diseases caused by Oom ycetes g roup o f fungi ( i. e. downy mild ew and late blight). T he maximum yea rl y app lic at ion ra t e is 0. 5 lb s./ A , which could result in a re duction of the pe s ticide loadin g in th e environment compared to cert a in reg is t e red a ltern at ives . B ene fits mi g ht a lso b e r ecog ni ze d fo r oxathiapiprolin treatme nts on regi s t e r

e d crops wi th min o r pe s ticide uses (s u ch a s gi ns e ng and y am s). The use of oxathiapipro lin c o uld offer ben efits as a too l in int egrated f ungi cide pr og ram t o fa c ilitate the seaso n-l o ng control of s pecifi c fun ga l pe s t and extending 

### 6lif es p a n of m a n y currently regis te red fungicide s . From a wo r ke r safe ty s tandpoint , and ba se d o n the tox ic ity o f the pest ic ide, agricu ltur al products w ill h ave a 4 h o ur REI. w hich i s the s hortes t period for any agric ultura l pesticides. 

### ALTERNATIVES Accord ing to i nfonnation p rovided by th e regi s trants , u sc of oxat hi ap ip ro lin could be expected to be a n alternative. based on th e pest control claims in several cu rre ntl y reg i stered pes ti cides, which includ e: C hl o rotha lonil ; Mancozeb; Zoxamide; Mand ipr opamid ; Difenoconazole ; Dim e thomorph ; Cyazofam id ; F lu azinam; Fluopicolide ; and Cymoxanil. 

### PUBLIC COMMENTS Th e No tice of Receipt fo r thi s new chemical was published in the Federal Regis te r on 4118 / 20 14 with a s mall , non - s ubsta n t ive co nection publi s hed 6111 /2 014
. The Not ice of Filin g was publi s hed 5/ 23 / 2 014 . T h e d oc ket is EP A- I-I Q

- OPP-2014-0114. Only o n e co mment was re ce ive d to date and w ill be a ddressed in the to lerance r ule. 

### PROPOSED REGULATORY D EC ISIO N EPA r ev iewe d 4 11 studi es and o th er informat i o n s ubmitte d to s upport proposed u ses for the new fun g ic ide call ed Oxathi ap ipr olin. Becau se no toxico logical e ndp o int s we re ev id e nt afte r reviewing the co mpl ete database, a qualitative ( n o e ndp o int s) human h ea lth risk assess ment was conducted in s t ead of a quantitat i ve (e ndpoints) ri s k assessment. The qua li t a tive assessmen t rev ea led no human h ea lth ri s k s which exceed Age ncy concerns . B ecau se it i s being assessed as part of a global jo int review, and is intended to be registered in add iti o nal countri es, the Age n cy is set tin g tol e r a nc es fo r harm o ni zation purposes . Oxathiapiprolin r eceived a reduced ri sk c lass ificatio n and meets the lo w toxic i ty c rit e ria publi s hed in th e Federa l Re g is t e r o n M ay 3, 1 995, stated in Pe s ti c id e R eg i s tr ation Noti ce 95-3, a nd prov ided in EP A Label R ev iew Manual ( r ev i se d May 20 14 )
. A quantitat ive eco logical ri s k assess m e nt was co n d u cted a nd found no ac ute and ch ro ni c LOC exceedances for all ta xa assessed w ith the excep ti o n of m a rg in a l c hronic ri sk to freshwater sed im e nt-d we llin g in ver t eb rates fo r ce rt a in proposed u ses. In addition to th e reduced ri sk cla ss ifi cation rece iv ed fo r thi s pes ti c id e. E PA b e li eves th a t the benefit of add in g a n ovel m ode of act ion compared to ava il a bl e f un g icides can h elp producers develop pesticide re sis ta nce management programs fo r foliar and soil-bo rn e fungal di seases; refer to the Benefits sect ion for add iti o n al inf o rmation. Therefo r e, the Agency has d e t e r mined that r eg i s tra tion of the five proposed products me e t s th e FIFR A s tand a rd and th e mar g inal r isk f o und (ie. se diment dwellin g in ve rt e brates) assoc iate d w ith ce rtain proposed uses is o ut we i g hed by the benefits ofthe use of these products. No add iti onal d a t a are be in g required for r egistratio n. Therefore. E PA is proposing the unc o nditional regi stra ti on for the fiv e propo sed oxathiapiprolin p r oduc ts und e r Sec tion 3(c)( 5 ) of F IFR A.


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### T h e hum an he alth a nd environm ental ri s k assessm e nt s supp ortin g thi s deci s io n as we ll a s th e draft labe lin g can be found i n th e r e g ulator y docket (Document lD: EPA-HQ-OPP -2 0 1 4-0 11 4 )
.

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