## Propo se d R eg i stra tion Deci s i on for the Ne w Ac tive In g redient P a pay a Ringspot Virus R es i sta n ce Gene (Papaya Ringspot Virus Coat Protein Gene) in Xl7-2 Papa ya (OECD Unique Identifier: UFL-Xl7CP-6)

Appmntl t y:



### I c k E.**~** scngcr. ii)Fto r**11 ic** **~** d fJ) cs t ici d c rogmms I> ate :

### I. 

### Su mmary

' llti s document announcrs th ; lt the E n\'ironmcntnl Protecti on

**~cncy** (I! I' A) has completed its inilhll C\'aluntion of the proposed new plant-im:orpOr:nOO pmti!C'taru (PIP) t l ctlv c ingn:<lien t l'nrx'ya Kingspo t Viru s Resistan c e

**O~nc** (l'apayn Ri n g.spot Virus

**C~uJ:trotcin** Ge n e) in X17- 2 f' upnyu and ha s

**~: on**  **clud cd**  th : u it meet s th e r cgu lnto ry and

**nf~ty** S t:l.ndmd s u n de r the

**F,-d~rol** I n sec t ic ide. Fu n gicide and R odc:r u icidc Ac t (FIF RA) . The : s gcncy i s s eeking p ub l ic co mment on i t

s J)roposcd decision . Tile X 1 7·2 P apaya has bcrn

**desi~n~..'\1** to contain 3 papaya rin J;5)X)t

**iru ~**  coa t protein gene whi ch

**m:akc~** it rc:l!oisumt to

**p:t.~ya** rin&SJ>OI

**vi~** .a

**~thogenk** p l ant , ; ru s li"L:t1 in(c.-cLS Jl3P3.Y:l and is the

**lc~tdint;** (' t:nt.SI! of p3p3yal oss in Florida . **T~pic:.lly.** a

**b...-~thy p.1J'.l~"**  pl:anl can !ouo • l\ •

c up to 2 0

**~** car5: ho"c, ·cr. ifinfec1C'd "ith Pi\1, , \ Y i \ RINGSPOT VIR U S.lhltli(c span i s rcduc«<to +5

**~(.· :US.**  

### t\Ocr n:vicw in g

**uhmiu~d** 

### and publically 0\1Ji l ob lc tl:.ll!l nnd 

### infomultion.thc E PA concluded t.tuu thi s O\!\\' actl\'c i ng r ed i ent i s cover\. '\I by t he ex istin g 

### tokruncc exemp t ion ( 40 CF R Pan I 74.5 l5 ) 

### for coa t prote in ofpapaya

**rin~ spo**  **t** 

### vin t $ in o r on 

### all food 

### c onu noditic :; uw.J l'll' nucll.!'ic acids (4 0

**R** l' nn 17 4 . 507) 

### a nd th e I' I£' 

### P : 1p aya Ri ngspo t Virus R esisumcc (icnc ( l'opay;a R i ng.spot 

### V i n as

**Co~u** 

### Prote i n Gene) in X 1 7
- 2 

### l' opaya will 

### n ot c.ausc any unrcu so nablc t td vcrsc dli.'Cts 

### t o human hcalLh or 

### on the environment .

**Tilcrc b~.**  the Agency is p r oposing t o

**c~btcr** the PIP produc t conuini n g the new ztct i vc 

### int,rcdicnt

**Ul~cr** FIFRA 

### section 3(c)(S) for usc in papaya . 

### 2. B nc kground ll: tJ!ul: u o ry On Nm ·embcr 12 . 20 14 . 

### the U . S . E nvir i .)O I'ncntoJ P roh . -ction t \gcnq · 

### (E I · ' A) r ccci\ ·cd an nppl it::•tion 

### l br re gis t ration 

### f Or th e 

### new p lan t-i ncorpomt ed 

### proh:clnnt (I'll') actiw 

### i n

gt'\."llic nt Pnpnya 

### Ri n g s p<n Viru s

**R~ sis**  **ancl!** Gene (Papaya R i ng.spot V iru s CC'I:t t IJ ro tc i n (ie1 \ e) in X l7· 2 Jl u pa ya from the IR-4 Proje c t o n 

### hchn lf o f the Un l\' cr sity 

### o f' Flor id ll's 

### l n.s t i ll

ltc:: o f Food u nd A & ricultural Scie nc es (UF / IFAS) . 11 l c npr li cant wa.;; not r eq u ired 10 sub mit 1.1 pe t i t

io n l O

r a toler:tncc or nn exemption (rom the 

### requ ire ment of a t o lc r . : mcc f or re si due s of the ae t h ·c 

### in&fC'dicnt on food 

### crop s l:x"'CBUSC 

### the new :tct ivc ingredient is co\'C'r(.-d by the existing 

### tolcr.Ulcc oxcmplion

**~0** CFR Pan

**17~.S** 1 S) 

### for popoyo ringspo1 , ;rus co>l pro1<in :and PIP 

### nucleic acid.<

**0** CFR l'on

**17~.507 ~**  :ts 

### d=ribcd i n 1hc su mnury S.."Ciion 

### abo, ·c . I n 2008. FDA

**indic:~tC'd** th ::U il t.;Kl no m or-e questions

**n.~3tding** the

**r~formc:d** Fl o rid:! line of X l 7• 2 ( hll p :/Jwww. fd:1 . . Cil\ 'IFOS'SJ/FQ$dSsls:ll\s:

**R¢'8.--:~rc** h .i G f.l 'l M ts!S l! bm i !iSW O}' u 5 m I 55 5 69 . h 1m) 

### und in 2009 

### the tron sfo nm.'(l Florida line of X 1 7
- 2 ,\ ns 

### d<:' n: gulntt."\ 1 by 

### USDA·APHIS CJ:wm; ;// www . :t ph i s.usda.l!(W / hrstnn h i:;f0S'!02 / 04

**~~** 70 l p CCim . pd 

## r nnd llll p S;i/ \\" w . o oh i s. usda .

**sov!l! lll!**  **f~ILi** Sl\' riP R S 10 09090 I . pdf . ) X17-2 Floridian Papaya PI I' PoJXt ya (Corira poJNIJ'tll. .) be lo n gs t o t > lant t am ily

**Cruic:occ lc**  und

**~** a po1 y[!_wnous hcrb:tccous 

### p:n:nnial plant . There a r c

**m~ny** ditrcl'\:nt t.:ulth · ::u-s of 

### pap.:sy;a grown.

**Pur-1~'U** ringspot \ ' irus is a !'agel of

**I~**pat h ogen ic plant \'iru s t h::u inf ects p.1p3)'fl. The \'nri o u s s trains of )Xlpay:a ringspO t vi na s im)X'ct the- numerous p:.pay a cuhi\'ars**diOCrcnt ·**  For examp l e. the Ha w a i ian papaya cu ltiwus t hat a r c re sis tant to papaya r in g,_-. po t v i rus . c\'a l u; l h. "d by EPt \ i n the 1 997. and gr O\\TI in Hawaii arc not r esis tant t o t he pa p:ayn ri ng SpO t \'iru s fou nd in Florida . Papaya ringspot \'irus is th e le ad in g cause**ofp.:~.p:aynloss** in Flo rid a. Typically. n h en l th y pap::tya p l ant can surv i \'e up t o 20 years: h owe\' er. ifin lt "(:tc: d \\ i t

h papaya ringspo t v iru s. thm li fe span 

### is reduced to 4-5 

### years. Ti l f! Uniwrsity of Flori d a has dcs ignC'd. th e X 1 7-2 

### r • rtfX'Yrt lin e t o contai n 

### rt pap aya ri ng.spot**\'iru.~** co at protein gene l i-olll a Stmin of the vi ru s found in Florida . The \' i rus coat prote in g<. · nc p ut int o t he X 17-2 Papa ya makes it r csis truu to th e**p.:~.p:.ya** ringspot \'iruscs tbund in Florida by h e l

pi ng the: X I 7
- 2 P:ljXIya detect an d degrade papaya ringspot \'irus coat p r o t

ei n RNAs via a p r

o c ess desc ri bed be lo w called RNA i m crfen:ncc. 55- I l hwaii a n l>a p: • ya l' ll ) The ge n e ri c t oleran ce - ex emp ti o n for residue s of p-apaya r ingspo t v iru s coa t p r

otei n M d th e gene t ic mat erial n .. 'Ces.sary for iL" J l l'"()tluc t i(l n w as (l ri gi n ll ll y rcqui!S tt.'tl 

### w SUJ 'fK l rtthe Sfk .. --c it ic papaya ril1 £.$po t v i rus coat protein found in tmnsgcn ic**Pa pay:~**  l ine 55
- l. now in commc r cinl p ap:tyn l int:S grO\ \n i n Hawai i . The age n cy's conclus ion for t he tolera n ce exe mp t ion was b ased on 1) the doc
- umcmed occurrence and long hi s t ory of p l unt vina scs in 1 000 omJ fcc:d (includi ng th e papaya rin gs pot virus) . 2) no fi n d

i ngs of tox icity of p l ru u \'iruscs t o mammals. and 3 ) n o fi ndin gs 

### of num1mali : m pat h ogenicity 

### f O

r plant \iru sc.s.**Plnnt ~**  Plomt V ir W(' S , : m d Plan t V ir

us Orf(' n s c s Plant \'iru s c- s are d ependent upon th e p lan t t o reproduce. Whe 1t n \' iru s iniL--cts a p lant cdl. i t uses the p l am cd l' s machiner y (n ucleic ocicls u nd proh:ins) t o p roduce ml'lny cop ies of it sc t t : P lan t \'irusc-s annck pl a nts: the y do not cause i lln c:ss i n hum ans. P l a nt viru s particle s con tain t he \ • iral ge J l t)I11 C: pac kaged in u protein c o; ll culled t he**1p sid.**  The c-apsid play s mllll y ro h:- .s i11 viral inf ec ti on of t he plan t. i n c l

ud ing \ irus auac hm cnt t o cells. entry in t o cel l s . rdcnsc of' t he cap si d co nten ts into t he c e ll s . p.J cka.£, i ns o f new l y forme-d v irol panicles . and nt O\'Cntc nt of the vi m s w i thin d1 e plant . At the tim e papaya was firs t**gi ee~d**  to res i st papaya rin gspo t \i rus. the mcchoni sm of how the , · iru s coat p r

otein gene provid<.'tl prot .. -ct ion ag a in st t he \'irus wn.•:; no t fu ll y unde rs t ood . Ln tc r . i t w as di s cove red that p ro t ect io n agairu t t h e \iru s \\ ' ns p r o"idcd by n type of gi!'ne s il enci n g. now understood t o be R1'JA intcrff:n:ncc or R.NAi. R NAi i s rtnntural process t hat plant s u sc to protect t hc m sc l\' CS ag:1inst viruses by d etec tin g an d dcg. rn ding v i rnl RNA s. , \I t h

ough RNAi silen cin g. is a na tu r..tl def en se m .. "'Cimn i s m common tO p l ants. pbnL "i d o not h:l\'c dfect i \'c gene s i l enci n g protect ion again st all \· i niSCs. Papaya docs n ot ha\'<: df.:c ti w RNAi pro t ec t ion against the }XJp:l)11 ri ngspo t \' i ru..o; o n its own. Agric u l tural scient i sts. h owc\'c r. can mttkc**ll ~**  o f th e naturnlly occu rrin g p r ocess o f RNAi t o**prO\'id~** n:s.istancc 10 plant \' iruscs by insc nin g t l i: ()Ctt protein g ene**(ht p:** **// www** **ap!'nct.orglcdcc nt** **nt opn** **illbo!icn~m up** **rJ r:~.sc** **sl bnt** **iruscs nsnx}.**  Thi s i s what was d one t o protect papaya agains t th e papaya ri ngspot "irus.**R~o- "S** **nnc c**  t o the virus is p r

o ,i dcd by nn RNi\i ge n e s i lenc i ng medl .nn i s m whcri!' p:lJ)3)':1 rinp,spot vints R NA ns.so<:i : ued wi th the virus coat pro te i n i s d ete cte d an d dcgmdcd. No i nf <. · c 1 i<tUS vi ru. ; J)lr1icles nrc fOrmed f r

om th e**tran s~** **enic** papaya.**ndr rs** **ndin~::** Gen e Sil f ncin g a nd RNAi 

### W/rot is RNA? RNt\ (ribonucleic acid) works \\ i t

h DNA (dco:<yribo 1lucl eic a d d) i n all ce ll s . D NA 

### contains genes t hat nrc th e**uepri t~**  

### t br alll i \'i n g thi ngs . These 

### b h u:pri nt s eonta j n the in f ormnt io n c\ ' ery orgMism needs to grow and s urvive. RNA 

### works \\i th ge n es t o tum t heir b

l uepri n

t s i n to 

### th e p hy sica l 1 Ctuures we 

### see i n I ivins t h in gs . l i ke eye 

### color. RNA is a 

### ve r y long h

c l

ix · sh:tpcd mo l ec ul e thn. t looks l ike**onc·h::~ f**  

### of a spira l S trti rcasc. I n so me v i n t

scs .**~; ud** **in g.**  

### t he**pn.pn.~ a**  

### r i ngspo t \' i rus. RNA n l so**ct~ a.** **~>** 

### t he b l uep ri n t i n stead o f DNA . WIJy 

### is RNA important ? :\II 

### l iving thi ngs ha\'c a gene t ic set 

### ofinstnJ ctions tha t 

### arc t he b uil din g bl ocks o f li f e . 

### ·n t c s c instn t c ti ons n eed some w uy 

### t o mO\' C 

### nro u nd inside n plant cell. n perSOn. 

### or 3Jl 

### ani m al to tell**~c h**  cd l how 

### t o )X'r i Oml it s ro l e correctly. t\ 

### $pCci:tl t ype of R NA . c . a

l kd mc-sscngcr RN1 \ 

### (mRt'JA) SC I"\ ' C!' 

### as bot h o copier machi n e and**mr~ l**  

### sc r viC: l.' for c ells. Th i s mRNA makes exac t c op i es of ge n e i nforma t ion nrl d ddi\ ·e rs it.sclf (and the coded me ss age i t ca rri es) to t he pan of t he ed t t hat prod u ces p r

olcins. To ill u stt:ltc t hi s prO<:'css. im ag i ne t hese simpli ti cd steps f o r manufacturi n g n. 

### ca r : 1 . · n 1ere i s n bl u ep ri n t (DNA) that co n tn i ns 1 h

e desi g n (Ge n es) tO r a c.ar. 2. A cop i e r ( mRNA) reproduces the b l u

e

pri n t an d di s t rib ut es i t \'i:t 

### couriers (mRNA) to t h e f:lC I OI")' (ce ll ). 

### 3. Wo r kers (riboSOill t' S) 

### at t he t bcto r y asse m b l

e t he ca r . Wlw t 

### i;, RNA**lmufi·r~tU t'**  (RNAi) and how**do, s;,**  worK? 

### RNA i . or R NA i n t erferen c e, i s a natu ra l p

r

ocess u s ed to contro l genes and ge n e expression. RN Ai is ofte- n uSI.-d by J iv i ng th i n

gs t o co 111 ro l h

ow much of a pro t ei n is mudc . It 

### stops c -: rtn i n mR NAs from eomp l c t

i ns th ei r tasks. th er e ro n: block i ns. or co n trolli n g t h e p r oduc ti on or a**sp~ilic** 

### protei n. R NAi i s n routi ne gene "silenci n g " process thtu occurs in plants. an im a l s, and hu mans a l ike. Plants usc RNt\ i t o pro t c:et thcmse l \'e S f r

o m plant v i ruses. B ui ldi n g olr 

### of t he e sarn ple above, wh en RNA i is used. the c op i er and th e eoudcr a.rc d i sabled and canno t d d i\'cr the car bl u ep ri nl to the: f t h! t OJ)' .**Co t.~q** **cntly.** 

### no cars n r c produc '- oU . 

### 3. Evaluation In C\'al u .ati n g a pes t icide r egi s t ra ti on a p p li cat ion. t he 

### EI''A nsscsscs a \\ ide: vnr k ty of s tu dies nnd infonnati on t o de tcm1i nc t h e l ikel i hood of**:ld\ CrS~**  

### e 1l L"Cl" (i.e . . r is k) from exposu r es assoe i t1tcd wi t h t he proposed 

### usc of th e p r odu c t. R i s k tlSSCSSmc:nts nrc d l! \

' elopcd t o cvalumc how the compo u nd m igh t ::tOL-c t a**\\~dc-** 

### rongc of non-tarset o r gan i sms, i nclud i ng hum an s and t erre.s t rial and aquat ic \\ ild l ife (plants und a nimal s) . BflSCd on thl!SC**a.~~s~ nt** **.** 

### t h e 

### EI ) A C\'aJwncs tmd npp r O\'i!S cond iti ons t Or eac h pes t icide p

r

oduc t to ensure thot penni n ed u"'c-s and S3fcty meas u res arc approp ri mc to m i t ig : ttl! aJ l Y potc nt i: ll risk The human hea lt h a n tll.'nv iro n m.: nt al ri s k assessments ( i nclud i ng : m c:nl.lang c:rc:d S pt'cics assess ment) s up po rti n g th i s dc:ci s ion c- an be 

### found in t hc- r c

g ul a t ol)' dockc:t (Docket Number c i ' A ·H 0·0PP·2015·IJ.I I 8). 

### r • ogc**f·~**

### 3.1 Assrssrncnt of Risk to Human Hc:tlth In onlc:r t o nsscs.s**PIP' s**  ri sk t o h um an hca 1L h.**th~** EPA g <: ncra ll y re q u i re s n llerg cni c ity n ml tox ic ity d 3ta / intbml ation. g ene rally c onsist in g of !I min o odd sequcm:c homology .:ompar iSUnto> to k

n 0 \'•11 aJicrgcns and**ox in** **.** hea t st; tb il i ty te s tin g. a n m:utc or.t l t

ox icity t es

t a t**ma ~innun**  ha? ... 'U' d d ose . a nd on i n t ·i tr o d ig es tion assay i n a si mu la h."'<l gas t ric cn\' iro nmcnt. I n t he c -ase of Pa paya Ki ngspo t Viru s R es i s tance G en e ( Pnp ay; t Rin gspo t Viru s Co:lt P rt Hcin 

### Gene) i n X 1 7·2 Papaya . E P A also eval uated th e si mi larit y of X 1 7·2 Pa paya to the 55 · 1 Papaya c urre nt ly be in g c uhi\' a t cd in Haw '3.ii i n o rder t o**dc ten** **1H.~** whether t h e**cxi g**  tolcrJ.ncc exemption. b roadl y wriuen. but wriuen to s up port th e 55·1 Papaya. could be cons idc n ."dto ;; & lso 

### apply t o th e X 17 · 2 Papaya. A. Gent ric f'apaya Rin gs pol Viru !l Tolcrnnct Exemption l l1c: 1997 generic tolerance ex e mption fo r residue s of p.:tp:t)':l ringspo t v iru s coat p r o tein and the gene t ic m.:ttcri a l ne-cessary for its production w n.s:**rt"qU~;. 'Ste** **d** 1 0 su ppOrt the S JR"Cilk p..1p:1ya ri n gspo t**ru.~c().1t** prote in f o u n

d in tmnsgcn ic P npa ya l ine 55·1. E PA co ncluded th at there is r.: 3SO n3b lc ccnnint y that no 

### h.ann 

# ,, ; nresult to t he 

### U.S . pofmk u ion 

### fro m aggregate ex pos ure t o re s idues of pap:t yn ri n g S'pO I v im l coat p r

o tein s p r odu ced in p lan t s as pan o f :t p l unt - pc: Sticidc: ( p) a nt - inc orpo rntcd pro te ct:m t ). This conclusion wa.o; base d on 1 ) t he documc mcd oc curre nce an d lo n g hb ;to ry of plant \' i ru scs 

### in 

### food an d feed 

### (i n cl u ding t he p :lp.'lya ring s pot 

### v i rus) . 2) n o 

### reports in t he s cientilk l i t cr.uure of toxici t y of pl ant viru. :c." t o mrunmal s. 3 ) n o re portS i n th e s cicmi tk l i

terature of m amm a l ian p..'lt h ogc n icity f o r pl a nI viru ses. nn d 4) DNA i s common t o a ll fom t s o( p l:u n {l n d nnimal li fe an d no i nstances hav e b<: cn asso ciated \\i t h t oxic 

### d T cc ts n:l u !t..-d t O th e: consu mp t ion of 

### DNA as a co mpone nt of 

### food. S ub Sc< ) ucn t to E PA' s t o le rance exem pt io n decision re lated to t he**Huw ian**  p:tpayu PIP. ad di t ional safety d : tt a**wa. ~**  p ub l is h e

d in t h e s cient i fic l i terature th ::n co nfirmed t he ori g inal sa fety ti nding i n 1 997. Fcm 1 i n. i. '/ (1/ , s howed that t hat the: fl : a w

n iitm P IP' s coo t protein d ocs no t pose a ri sk of f ood alle r gy s inc e I ) b ioi nt O

m1 a t ics of t he coat p r

otei n a min o uci d .sc quc:ncc: shO \\ Cd n o s ig nilican t homo logy 1 0 knmmaHcr g c •' L '. 1 ) t h e c oa t pro t e in is r ap id l y dcgr.adcd i n si mu l ntcd t;ttStric llui d and i s not stab l e i n simu hnc:d intes ti na l ll uh J . .3) th e coal p iO tci n i s unstab l e to hc. at tre atme nt. an d 4) the Haw ai i a n PIP co nt a inin g papaya has been cmcn for more tha n n de c a d e with n o no ted adverse el1i.."CL'i. t o hum a n h ealth. (Fc m1 i n . ct al . 2011) D. Pl:mt-lncoqwr .. lt. 't

l Proh:ch mt Nucleic Acid EJ: cm pt front**Tol~rantc** R.:quircmcnt s The 200 1 exe mp t io n from the r eq uirem e nt of u t o l

crn n cc: f or : all pl u nt·incorpor.ttcd p rot cctt1tl t nucleic. nci ds: 

### r-..'Cogni7.L"ti that nu cleic ncid.o; cou ld not on l y cod e f o r nnd cont r o l the: p r

od u ction 

### of pest ic id a l s ub s tances in p l:tntS .. bu t co uld al so be th e pe s t icidal s ub s t an c e t hem s eh · cs. as i s the case " i t h a nti· scnsc PIP s p r o te<.:tin g p lant s fr o m p la nt viru ses ( now U11dcrs t ood as d oi n g so by RNt\i). E P .. \ co nclud e d for anti·scn s c techn ology based**l:mL- incorpor.** **at~;. -d**  pro tcctnnt o; t hJt both r'\!' s iduc s o f t he a JHi· se• t s c R NA a 1 1 d t he DNA encodi n g i t were cxcmp1 f r

om the r equirement of a f'o gc 5 

### of**I~**rokrnncc. The: conclusion dur th:u th,·n: is

**n.-ason;~blc** c:cnnin1y ttur no harm ''ill

**~~~** 10 1 hc U.S. popul : :uion from aggregate c\pt»ure 10

**residl.k.~** of nucleic tK'ids thai a.rc p.11t of a

**pJMt ~**  incorporntcd prorcc w. nr \\"3S

**ba..~-d** on 1 ) n ut lcic tleids: :tre nonnl111y a component 

# or food from 

### p

l nnc.s . n nd 2) experie n ce ''ith t he

**cxtcnsi, ~**  usc of food from 

### p l n

nt ::, i n dicott:s ad\'crs c cffcc lS

**a~** " " 'likely . C. I I u m an H u llh Ri s k Co nclu sio n !! I. !;imll.:a.rity 10 the 55- I lt awa.il:tn l':ap:aya P IP and the Nmtun.lly Q('CUrTing P.a p :aya RinJ!'pol Coal Pnlltln lb.: l lawaiion Pap:1ya PIP .00 lhc Florida Based X 1 7 · 2 Papoyo PIP on: >irnilar. lb.: cool

**rrotcin..~** 

### a.re the S3l'llC structumlly nnd functionally. The Floridian nnd ll awuiinn \'tlri3llts :uc indicmi\e of different p=ip=t)'n ringspot 'irll) Mr.)ins \\hich \"31) ' g\.'OgrJphically ami bolh

**~u..~** diSC'a.:sc in pap;:1)'U. The ll nwai i M t mnsgcnic (:Onstruct dOc."S not pror"-ct

**o~inst** the Floridi:m p:.p:tya ringspol 

### ,;ru:; s 1n1in . To cont irm si mi lari ty. EPA compnn:d tht: ll owai ion popa.ya ri ngspo t virus coat protein a min Q uci d S I.'\IUt:nce \ ·ia the Basic L oc - n

l

**Al nl'fh:nt**  Search Tool (I) LAST) 1 0 it s F loridian co unl crpnJt. T hi s compurison dcmon ..\

lmlcd o 96% h omology. The: mi n or vnriuti o n in :: a min o n cid seq uence be t ween the t wo str.ains i s nt:gligible n nd could be

**t: it:d**  si nce the virus phenotyp es vnry gcogrophicatly. The s l ii;] H mnin o m: i\.1 ditlCrenc es do not indkotl! a n y sig_ nilicant health i ss ue s n:ln11.-d 1 0 I OX icity or aHc-rgcnicity during con s umption or othe r cs · p<> s ures. ,\mioo ac-id homology d:st:1 submitted by IR-4 bct\\«n 1he X17-2 

### ft:sp;sy::a ringspot 

### , ;rus coot protein and the nalur.llly occurring Florid:l stro.in of the JX1paya

**rin~.)-pot** \ irus tlut St.""t'\ " cd as its

**origin;~.l** source ( H I K stmin ofpopa}n rinppot \ ' irus:) wns reponed 10 be 99.n. •. 2. Additional Oaltt Showi n .:

**~u** Allctgcnicity Risk llioin t b m1otic s 

### t\nnly s is: s:ubmilh .'<l 

### by IR -4 dc-mons trnted th a t the 

### X 1 7·2 line 

### of p:1paya rin gs pot rt"Sis tant p::ap:1ya docs not repre s ent n S4.1 Uft:i! of n o\'cl po t e nt ial al l ergen ic proteins . No s igni l it:ant

**imi arity**  to MY kno\m a llergen ic proteins was l.lcmon s trol cd in nn

**Allcr~;c nc**  search. 3. llurnan Hull h Risk Condu)iu n EPA c.'UfM:Iudc=s that tl'k....-c is 3 rc3500Jblc ccruinly tlul

**no~** will

**~ult** to the U.S . population from agg.n-gah: expoSure tO n:siducs of nucleic acids and the p..1p;l)'U

**rin~t** coo.t protein from chc Xl7·2 Papoyn PIP: in addicion. lh< &"""ric ()3()3)'3 ringspoc 

### ,;rus (40 CFR § 17 4.515 ) 

### and ch.o PIP nucleic aci d c okrancc cxcmpcions ( 40 CFR § 17 4.5 07) appi) ' co chc Florida based X 17- Z Papaya PIP. EPA 

### b:>.<eS iL< findin ss on: I) lhc dcmonscrut,-d s imi lori c y of chc X 17· 2 Papoy :r 

### rini) S pot ' ' irus coat protein to bo th

**th~** ll awaH nn

**pa~ya** PIP 

### pnp.1 y:a

**rin~ ~po**  **t** coo t protein :u1d th e 

### nntunJll )' o ccurring papayn rin t;Spot '-irus

**:,~min** 

### II I K coot prm d n , 2) thnt p l ruH s c a n natumHy defe n d thcm .s<: lve.s f r

om p la lll

**viru~cs** b y using RN;\i

**gcn ~:**  s ilencin g nn..J :1gr icultura l s cient i sts

**~.'tl** thi s dt:fcnsc me chan i s m t o mnkc 

### vu l nerable papaya rc s i st: mtto the pupaya rin gs J'I'C)t vi ru. o;, 3) the ubiqu it y of plant v i ru ses :md nu c h:i c o cid.s in food

**\\ th**  no re po ned odnrsc cfli-c ts.. unU 4 ) the nddi t ion.:a.l biolnfomutic s da111 dcmons tr.llinb 

### :a l:ack of no\'c l nllcrJ;cnic protein in the X 17<!

**P~p..1ya** ring,spo1 co:u protein . Pas< 6 of 14

### F o r more infbm1 a t ion on the humnn health risk assess ment of Papay a Rin gspot Virus Re sis t a

n ce G!!rlc**(Pap~ yn**  R i ng.spot V i rus 

### Coa t Pro tei n Genl!') i 1t X11
- 2 

### Papaya . p l1! a$ c se c the 

### s up po nin g d (}l: u mcn t in the associat ed regu la t ory**od~l!' t** **(~c::tn:'h** 

### t O

r**~IWA -II** **OP I'** **201** 5
- 04 I 

### 8" m lutn : l fl n,,r.r,•gulm ian\'
. w). 

### 3.2 Assessmen t of Eco l ogirol R i sk To assess ri s k to the cnviro nnh:nt 

### f or PIP s, t he E P r \ n: q u in:snon
- tn r g ct orgn ni sm t oxici t y da t a l int O

tnH ition. gc: m.·mlly 

### c o nsist i ng of**c:~'1i g**  

### \\ i th b i r

ds: mammal s : fre shwater and marin e/est uarine fi s h nnd 

### i nwnl!'bt:lh!'. 't non-target**n. ~-c** **lS.** 

### inc l u ding h o n ey bcl!-5: 

### n o n - l!lrgt: t p lant..;: :: u1d so i l**rwcnc:bmtc~ .**  

### In ad dition 

### co t h e t ox ici ty 

### d:un. ot h er data n r c 

### also (·onsidc:mJ n:gardin g the enviro nmenta l per sist en c e o f PIP s. as we ll as th e po t en t ial fo r o f l"·s itc m ove ment (gene ll o w ) and**inv n~** **en css.**  t\. Hazar-d. Expo s ure 

### and Ri s k t o Tern •st rial 

### Organis m s I. 

### Non
- T::tfl:C .' I Pl:mts For h azard eval uation of a pl ant · i nco rpo rat c d pcs tici d:tl sub!\tan ce tha t is prod u ced fr o m a pl an t pat hogl!'nic microo r g:mism. t he Ag..:n cy d c: t e rmi ncs wh ether i t s u sc prcdbp oscs o th er n on -tn r

g:ct p

lan t s . and n on -tran sg en ic pa p:t ya to o t her d is ... '"a.*' e S o r pt.""St.s 

### t h:l t might t rigger adnrsc ct1Cct s . In :1ddi t ion . the Ag ency**dc tcnnin** **e~** 

### whe t he r i t s u sc m ay t rigge r potent ial t (l r o tT- s i te m o\'c mcnt (ge ne tlow) and introgrcssion ( inttOI.l uc t io n o f genes) i nto no n-tmnsgcnic. wild o r .. l t: ml
-**papa~ a**  

### pop u lation s. The p.1pay a r i n

gs pot v i rus is s p ... · dtk 1 0 t h...- p;JJXt)':J plant. In X 1 7·2 Jl llp.1)'3. 

### resisuu 1 ce

- t

o th e p.ap.1y;1 rings pot \' i m s is p r

o\' idcd by an R N

: A i ge n e si len ci n g me -: h a

n i s m wh.:rt: papayn r in gspo t \ ' inLS RN A associate d \\ith t he \' i rus c oot protei n i s detec te d and d cgrnded . No i n f c

tt ious**\'iru ~**  

### J l:lr1idcs arc fl1nm:d f ro m thl!" tran sge ni c**p:..pa~ a**  

### and thl!' p lant-i ncorporated pestici d a l subs tan ce d oes no t predi spose no n- t a r

get p lant s t o oth er d i seases or pests thnt mi gh t trigger nd , ' er.;c**l!' tl~ct** **s.** 

### f u rt h er , as de s cribed i n the gene fl ow S l "<:t iO I\ t hat I 'OIIO\\ '$ , t he risk of gene flow vi u po Jicn t mnsfc r from th e X 1 7
- 2 plants r esu lt i n

g i n hybrid ir . .n ti o n o f s e xua ll y CQtl'lp:t tibl c wil d rclati\' cs is \ ' cry unlikely in the U nit...--d Sta te s and it'\ t l!'rritories b ut esp...--ciall y i n the p r

oposed gL "'gr.tp hi c re g io n o r com me r ci a l ir.n ti o n (Flo rid a) . 2. Bi r d s :md Mamma l s 

### There is a long his t o r

y of cons ump t io n of th e p la nt " iru s p : mi dc:s (i.e. , papaya rings pot) i n fo od by 

### b ird ,.; and m run m a J

s. wi t ho ut**c-au~i ~**  

### dekt l!'rious**cll~ets** 

### o r C\ ' idcncc of t oxici t y:**\' rus.infi..~ctl!'d**  

### p

lants nrc p :trt o f t he !l\' i :tn nnd m t\m m a lirm diet, and t h

ere h ave b...--cn n o find i ngs wh ich indi cmc t h::tt p lant 

### , ·i ru scs arc capabl e o f r cp l ka ti o n i n m::tmm a l s o r b ir l.ls. t h us el imi na t i n g the po ss ibi l i t

y of i 11 fc cti o n . Funhcnn ore . i nfecti ous panicl es are not f o nncd from the t ransgenic JXIP.:l)':'t. 

### which h:lS bc c:n mod i fi e d \\ith t he: po rti on of t h e genome**eod in** **~** 

### f b r resis111 n ce t o papaya rin gs-po t**viru ~**  

### an d s ubc o mpon en t s o f the r es i stance gen e . S i nce t h is gene i s c x pn. -ss ... · tl 

### o n l y within p lant t i ssu e s . 

### Po s e 7**rJ~ t:\pG**  **~s** an: c-xpc:cttd tO tk: minim.l.l .

**A~** 1hc gc:nc:cic m:neri31 

### i .s incorpor.m.-d into the papaya

**plantti 'tle.**  il would not

**c~.atc** J)l.1nicle s th:at could 

### pass n:spir.:uory o r dermal barriers :lJ'M1

**th~rcforc** is not

**like.l~ '**  to impac t mamm;d s . birds o r ins..."'C'lS th.1t SCf' ' < M a food sourt'C for b irds . Gird s an d m a n1mnls: would be

**cxpo ~;.'d**  "' th\! X 1 7·2

**P3p:~.y a**  Plr prim arily Lhrough inscstion of

**ci ss**  **u~.·s.** see d or fruit s oftnlns.gcnic Pnpaya X 17
- 2 . or lh ) lll p rey th a t hnd

**in~t.:~lcd** transgenic 

### r : •r:ayn . Contac t w ith th ese s urf1 1 C

C

.:' i s no t 

### expec te d t o

**c~u lt**  i n sig nil1 cn n t 

### expos u r e. th oug h Mal csposun:- muy occur incide ntn ll y t hruu H h groom ins. The submilt(."( l do.tn nnd i n fom1a t ion a r c suOicic:n t to conclude: th a t th e X 11 .:2: P apayu P IP 

### i$ highl y u n

li k ely tu i n f 4.'Ct

**bird.~** or \ \ ild mnmm :•l s u nd cause od\'crsc cfl'lxts.. ,\, Noo- T argrt l nsr-ct .s l nclud int:;

**li ·**  B ees N o nurgct. inscc:ls inc;ludi ng

**ho~y** 

### lx"C'S could be

**~JlOSc.-d** to tr.ln.S g eni c p;lp:l)'a tissues which conta i n papaya ringspot

**irus** coat protein through ingestion oftl SS I.K"'S. fruiu or pollen of

**nan~~cnic** Papaya X 17·2. o r from pn:y dtnl Md ingested

**trn ns~cnic:**  pap:1ya . Dispersal n .nd m

on:mcn t uf tran ss cnic p.1payn t i ss u c s ( e. g . .
**primari ·**  scro or rnsit) could

**r~.-sult** from a

t; .r ic u h umV h onicultural opcrotion.J (e . g .. pl ; mt i ng) nnd \\'(>3l h c r ac t h · it y ( c · B·· hurricane- s. ttopi cal t\t

o r m s up r oot in s th e 

### paJXlYil t r\! · C) a nd n n i

mal d i spers sl

**ofp::u1i:sll~ ·con**  **umcd** frui t . ll owcvcr. p l

u

nt

**vin~ s**  are r out i n

ely i n

g c

..s h :d by

**\'irtuall~ ·**  nil o r g ani s m s wh e n \' i ru s- in t i."'i:tcd f rui ts and WQI.' t ab l c s arc con sum e:O . The "irus is spccit ic to onl y the pap:tyo plant. nnd insects such :1S aphid s . I\\'0-SJX)Ued spider

**rnit~.~ s**  and

**p.1p..l~"3** fruit Oy arc not Qd , · .:rscly aflCctC'd by the

**c.spn..... ~i**  **on** of the p..1paya rin gspot

**vl~** 

### c:oot pro::ein ( U SD J VAPHIS, 2009 ).

**lk~use** 

### no infi.'Ctious

**ponicl~** 

### are f onned from 

### the transgen ic

**p;~JXtyn** nnd the 

### mode of iJ c · ti on i s spc'\7ificolly for

**1!Xprc S..'i**  **in~; r~islancc**  through 

### a gene s ilcncina; m"'"Chanisrn to p:tpaya rin g ,.pot

**~irus.** no ad, · crsc: 

### c:IT"rxiS an: o nti cipali.-d to non·targct in.'io4:cts. inc ludin s llonc:y be-es.

**n:g.sntle~** of" the exposure . (EPr\. 1 997 : 13. P , \. 2007: US[)A/A PIIIS. 2009 ). 

## n . llu z ard, E x:po s u rt' ltntllt is k I O 1 \IIU :ltic Organ is m s I . f" r rs hw ,u, ttr f Uh . ln ' ' trf thna l t 

### u ntf Es ru a rin dr\ l:l r i nl' A n l n u e l5 No :•d \· crx e:Oi..'"CIS t o

**aqwni~** orpni s m s arc anlicip:u ed tfon 1 1h c X 17-2

**P~paya** PIP.

**bcc3u..~** no infl'Ciious panidc::s arc fonncd from the t.r;uugcnic pap;ay n nnd 

### the mode of action is S pcc'i tic:llly fur t: X pf\.--ssing n.---sisaanc:c 1hrough a g ene s ilcocing mechanism l o plp:l) 'Oo ring.spol '"irus. a pl:ml

**ru ~**  **~-cili:c** 

### to p:l.J:Uya. funhcr.thc: producl

**i:.~** 

### not intended for d i r«l r.pplico.tion into cstuarinc or marine c:n\ ·ironmtnL" nnd cxposun; and risk 10 aqtt:tric nnimttl s .

**in, c:ne:bro~h:**  **::;; .**  and li s h is no1

**C~JX-ctcd .**  2 . A quati c Plan u The JlroJ>OSCd usc o f Pa pn yn E\' t: n l X 17- 2 is t o cont r

ol a , · iml

**di e~**  **M.".** The pe s t icida l m ode of :1c t io n i s s pcc i lically t b r cxprc s .. .

**in g**  **n:~i~tar1ce** t h rough a gen e s ilcndnJ:; ntt.::·c1m ni s m 1 0 papaya

**~;t po**  **t** virus. a pl .: mt viru s sp..--ci li c t o JXI P il)'3
. The product i s not imcndcd for dinxt opplictnion 

### Pose 8

**ofl ~** into**~st ari** **nc** or m: t ri n e C'O\;ro runc nts :md expo s ure tO uquut ic p lants i s n o t e xpe cted. Theref o r e.**~d c:rsc**  c nCcts t o f re s h wate- r n ll d mari n e: o r cstuu ri n c p lants arc n ot anticipat e d . C.**~ne** 

### f l ow F<

.) r PIP r eg i stratio n actions. E I ' A a l so U ...'S c .S.Scs t he l i k

el i h

ood and c n i:cts of off·si t c m o vem e nt (ge n e tl ow) a n d i ntrogn: .ss io n ( th e int roduc t io n o f ge n es fro m o n e spe ci e-s i n t o t he gene pool of ru1o t hc:r spec ies) from t h

e P I P p lant to sex u ally CO ill J'l.1 tib lc wi ld**n:l ati** **v~** (S<.: WR ) i n t he US and it s te rri tories. R e gistmm s 01'\.' . t he r c: t

(m: . r eq uired t o s u p

ply :t gene flow risk :1sscssmc nt t h : n d i scus.scs the possibi l i t

y 

### of po ll e n 

### no w to comp:1 t ib l c p lan t s and hybrid i 7 .. :u io n . i nt rogrcssion . and stab le**ri nc~;**  of the P ll) lrn it i n th e p l::mt. If E P t \ ·s risk anal ysis concl u des d un u p r opos e d PIP t rait hJS the poten t ial t o confer :1 selec tive ndvn.nmgc 10 wi ld and fend rel a t ives by pollen tr ansfer l eJding t o h ybridizn t ion 1 introg r css io n . and stab l e i nh er i taJ l ce. th en p r

O:lCt ivc measu r es mu s t be t a ken t o m iti gu te ident ilk -d imJXtCI S upOn 

### n: gi s tr:.t ion o f suc h a PIP . The appl icant (UF/IFAS) ofl'ap:..yo**E\'~nt** Xl7
- 2 intends 

### w rde :\SC t hi s ge n et ically m odified p3p ::tyn h yb rid for co m m c rci : ll izati on cx cl usi\'dy i n Flori da. No cl ose l y n:ktted wi ld a n d f er. t l rd nti\'cs coex i s t in thi s gcog rn p h

ic

. re gio n (USD A 2009). an d ri sk f r om se n e fl ow and i n

t rog r css ion is . t her d O r e , highly u nl ikd y . Th e d oses t rehned rd: ui ve**~** t h e Mtlu nt n in p :1paya ( Vascunc,•llt•a spp.). whi ch i s. ntuivc t o Cc n tm l a n d Sou t h**t\ cric** **1** (USDA 2009). If cu lt ivat ed p01payn (Curica fWJNl )'

U L.) m:rc co m mc n: i a l ilcd in an area wh ere t h e Moun t a in paJXI)'Ol spec k'S co-occu rre d. th e risk o f hybridizat io n fro m ge n e tl ow wou ld be low . Th i s stateme nt i s suppo ncd by hybrid i ?.a ti or l a u.: rnp ts bct \\c c n cult i \' rt ted and Moun t a in pa p :.t)'<l S:pt •cie s t hl t h twc 1 3i k -d 10 produce i mergencric h yb ri d:> (OECD 2005) . In ndd i t ion . t he FIFRA Sc icnti lic Advi s ory r ane l 

### (S A P) (200 4 . 2005) concl u d

ed t hat papaya woul d n ot fo rm a ,; a bl e h yb ri d " it h w i l

d rcl n t ivc s i n the U.S. an d its terri t o r i e s. 

### B PP D concl u des lim 

### t he ris k of gen e Row v ia po llen t rans fer f r

om t h e PIP X 1 7
- 2 p l n

nl s resu lti ng i n hyh r id i nt i o n of :a SC W R i s \' cry u nl ike l y in th e Un ited States and i ts territ o rie- s bu t es p.;. -c i olly i n t h e proposed gcogmp h ic re gio n of**ommcn:i~l z:** **ion** (F lorida).
A P I P p lant ex press ing a pro t dn con l ;:rri n g di sease or pc:stn;sistnncc: h .as t h e pOten t ia l t o i n cur n compoc:t i ti\'C**n~lva till)c**  O \' cr o t he r r l an t**(ll: ci~$**  with which it i ntcraclS an d s hares an en\' iro nm e nt (S:\ 1) 2QO..I) . The r e f

o r e. as part of th e rcg i s t rn t io n rc..-qu est . CP A n:q uir es app l ic rutts t o discuss t h e**potc:ntia ll** **~'l r**  n Pll ) p ltu u t O**com l!'**  i n\'a., ive in t he env i ronm ent. Typ ic a ll y. uppl i c;mlS MC al s o r e qu i r e d t o s u b m i t i n f

o nn a ti on address i ng t he l ike li hood th at a SC WR can beco m e a w ee d i f t he transgcnc- i 11t rog,re.sscs. PI P pollen flow t o SCWR has th e po tent ial to confer a s el ective adv a n t ag e t o wi lU and ICtid n:h ti \'eS if hyh r id i7a. ti on . int rog r .:ss i on . :utd s t ub l c i nh c ri umc.: c ::t r c possib le . The Un iw rsi t y of Florida d emonstrated tha t t h

er

e w ere no**si~n c.ant**  d iO i:rc nc t: s in**ph~no ogy**  between genet i c-all y engineered X 17-2 l' apaya an d no n ·g cn ct ic a lly eng ineered C
. pupuyu p lnnt' P

:age 9 of 14(IJSD,\. 2009). The l><k of d<C«Illblo sig nifican<c in pl>nc , · igc>r did noc >"Uppc> n clu c X1 7 -2 Jl.1p.1)-:J. would be \\ ' C'\."d ic!:r in n.:nurc than it5 non-generically cnsincrn.-d counterpart. llxn:forc. 

### OPPO concludes th..1t the 

### likelihood l b r X 17-2 

### Pnp;tra co

**bc:com~** 

### in\ ' M h ·c is l ow in the Uni ted Sta t t:s 

### where ils 

### commcn: inl i n ui on would be limitc.:d w Florida. 

### llPPD l'i • rthc:r

**~ond des**  

### since t here i s no c\ • idcnce th.n t C. papaya 

### h rtj wild or l i!rn l relatives in the United S t ot

ts and it s 

### 1 crritor y wil h which hyb r id izat ion could occur. t hnt nt 

### t ht: prese nt t i me the conccn1 for the VCP tmn sgcnc t o confer o. sclcc t i\'C 

### odv l mlagc of inv asive ness to SCWR in

**lhL~** U nilcll State s is no t s ubstnntintcd . 

## f :. ' l"hrt::lftntd and Endans::rrt'd Srrcits AsstssmC"ot EP, \ has determined thll no eff«t.S

**:~«** antic:ip3ted (or non - urgct )-pt'C'in: C'Xpo.sed 10 pop:1)"3 ring.spot ,;rus cool proh:in in Pnp.1yn X 17·2 including mnmnuls.

**bird.~.** lcnntrial and aqwuic: rlnnt;;,. freshwnter and marin clestu;ari nc animals :md insects. There: fore:. u "No Effe-c t .. dctcnnin : uion is m:tdc for dir C't'l and indirt.""CI

**~11\ "Cts**  to

**t\.~e r:dl)**  **'** listed

**c:ndnnt;~rt.'<l.** nnd thre:Jtcncd ("lisH: d"J .s pecie s nnd for 1hcir de s ignated criticu1 habit:l.t. F . E col o g i c:llll l< k C nn c h ulon

· nh.: EPA made 

### o.

**~No** Effect'" dc:tcm1inntion fordin.--ct and indirect cll\."'Cl.Sto tCderally listed cnllant;cred and thre::ucnOO ("listcd") ) pt"(ics oml lOr their desigJt.1tcd cri t ic: .

n l hnbit:tt from cx ; po!iUn: to lhc Xl7
- 2 P ttJU)'Il PIP . lk<ou;c of chc ubiquicous rucurc ofplan! 'iruscs :cnd chc likclihc>od c>f cxpc>surcs. :cnd because no inf4."'t'lious particles 

### an: fonncd from the tr:wgcnic papaya. imp.1c1()) 10 non·tars;!t org31lisms 

### from 

### X 17·2 Popa}"3 PIP arc

**nuall~** 

### non-c ..

**~ish -nt.** 

**n,~** risk of ge ne tlow via 

### pollen tntn s fcr !"rom the PIP X 17·2 pl.:mts fC$Uhing in h ybridi7.n ti on of n SC WR i s \'«!t'Y wtlikcly in th e Un iu :d Sta t es and i lS tc:rri t oril.-s but

**~specia lly**  in the p r

oposed

**g~·ogmp hic**  reg ion of

**(;()mm~rcio i;o.J.ltio**  **n** (Flo ri da), Sint:c then.! is no e\'idcncc th:tt

**,KifK~J'U** h u..-: wi ld or feral rei:Hi\'c S in the U n i ted St : lle s

**:~nd** i t s territory with \\hich hybrid i7a t ion could QC'cur.th:n .tn thl! pt L"$Cnl tim c tJu : concern for the vir.1l co:.t protein tra.nsgene t o conti:r a sth.."Cliw udvomt.agc ofi0 \ 1tS h ·cnc:!' .S to SCWK in t.hc Uni ted Sutcs is oot substanti:ttC'd . Thcrcfon:. EPA tondudc:d lh:u this new actiw ingredient \\ill nol c.au.-.c unr\.-asonable 3d\ · crsc

**cOi.~LIIi;** 

### on the cmiroJliiXnt . 

### -1 . A lt e r n ative s ll) ' t h e: 1990 s, pa p aya ri ng s- pot vinlS h m.l n:ducc:d H awai i's

**JX~pn~ n**  **:~crcngc** by 50'% . Titer e nre no u s efu l chem i ca l control s. W it

h t he s ucce ss fu l int r oduc t ion of a 

### r:.p aya t • t r in the late 1 990s.thc I lawai 

### ian pnpayn industl)'

**cst~lllt.'tl** nonnal production (Fcnnin. ct nl. 20 I I) . Page 10 c>f

**I~**Floritln ' s**puyn** indu s try has now only 300 a c res . dO\\n fr o m 500 acres in the earl y 1970 s . In creased compe titio n from o t hc l' 

### countri es. s uc h ns Me x ico. highe r producti o n co s ts (u n i t costs). and t he l n

ck 

### ofp.:tp:ayo. r ing.Spot viru s r esistant 

### cultivar s h:.w c all played a 

### rol e ( h t tp : //

c"li.- , jfias.un.edu / t

C9 1 ·1 }, T he rc gis tmtion 

### o fl'opn yo. Rin &S JX}t Viru s R cs i s t : mcc Gene ( P ;: ap ayu Rinl: !!l>O l Virus Coot Protein G ene ) in X 1 7-2 P : ap ayra w o uld provide papay a rin gspo t virus disease r cs i stam**cult iv** **:~.rs** o f papaya in Florida a nd could r es ult i n cxp:md cd producti o n . 

### 5. ll cncfits and Public Comme nt s Dil)J'IC St icid cs 

### arc pe s ticides 

### dcriw:d from s u ch n at ural m a terials 

### as an imal s. pl a nts. OO c h :ri ;t . and ccnu in mineral s. PIP s . a cla .ss ofbio pc st icidc s. nre pl "S t ici dal s ub s trutcc .s t hat plants produce f r

om g enetic 

### ma tcri ol thnt h :LS tx"Cn : tddcd to t h e p l ant and m a y have the fOIIO\\in g bene ti ts: • Usuall y nrc inhe rent l y l ess h a rm f u

l than con\ ' C ntiona l pt. "":S t ici dc s . • Gcnc m ll y**:. m.~ct**  on ly the t : tr g ct pest a n

d close l y 

### r d: u cd o rg a nbw s.. in c o ntms t h1 bro:td· ) ,X."Ctrum co nventio n a l JX"'Sticidc s th a t may atlCc t many ditTcrcnt o rg a nbw s { e . g .. bi rds.**in.~cts .**  and 

### nt:lntm als). • Often a rc c fl i: ct iv c i n ver y s m a ll quant i t ies a n d oflc n decompose t lui ck l y . thereby r c s ulling in lo wer '-'X pos urc s and l argely avo idin g t h e pollut ion pro b l em s that can 

### tx: cau s ed by convent ion al pc s ticidC' s . • Cn n**g_rc: ul~** **·** 

### deen:a sc the usc of co n ventional pesticides while c rop y ie ld s n:m n in high. whcn u .<> cd a. " n c o mf'(lncnt of i ntcgr.ucd pe- s t**nn:~g cmcnt**  prog.mm s. • Cnn ofli: r u n o th cr t oo l for pe st management i n ar ea s where cn ,ironmcnt u l conce rn s l imit th e u sc of co nventi onal pest ici des. In the**F~.-dcm l**  Re g i s ter o f July 20 .201 5 ( 80 FR**2802) .**  

### th e EP A an n o unced n: c dp t of em ap pl ic ation t o regi s ter a pest icide produ ct c onta i ni ng th e new :u:t ivc in gr edient Papny a R i ng. , · fH• I l'i rtu ' Rc .dJ tmu ·,· (;t • m • ( l'apuyu Rh:s .) ' pm Viru s <.:ou t l'rmdn G l'll l!) in.\'1 7
- 1 Papaya prote in a nd opened n 30 ·d a y public comme nt period. Th e E l):\ re,eh • cd tw o {2) comments to this 

### publi cat ion . 01\C con u ncmcr 

### was n 

### J).3p.:tya growcl' in So uth Florida an d w as in t :wor o f E PA gr.mting the: rcgi strn tion . Furth er . thil; co mmcnter**indi c~t~** **tl u:~** **t** "ltJhi s i s the o n l y oppo nun i ty that we ha, ·c o f being able to eco no mically produce qu:tl it y p. 1p..'l)'O 

### t o t ht! benefit of us as fanners a

nd thl! 

### t \ancric a1 1**Jt unt** **cl' ''** **II** h3 \' C a m u ch bcuc r 

### produ ct at a l ow er pricc ..... llH! 

### o thc l' co mm e nt c a me from tw o indiv idua l s fr o m the Un h • en;i t y o f J ! lorid:t. They t oo we r e in ravo r of th e rcgi stm t ion. 

### 6. l'ro1• oscd Re gu l atory· Deci sion The Om.ulx tS c f o r P u

p

aya Rin g.s po t Viru s Rc .s i s t :lllCC' Ucn c ( Papay a 

### R i n

gs pot Virus Co; tt Prott! in Gene) in X 17
- 2 Pnpay n i s-co ns ide red co mple te. The: 

### propo s ed u!'c o f Papa ya Ring spo t Vi ru s Res i stanc e Gene ( P apa ya Rin gspo t Virus C oat Prote in Ge n e) in X 1 7-2 l'rtp:!)'3 is s up po rted by t h i s d:tt abase. In c o n s ider i ng th e a.•;,sC"sscd ri s k to h uman h ea l th u nd the cnvironmenL th e E PA Pag< II o f 1 4conclude-s th;n

**P3p3~1l** Rin gspot Virus

**R~istnncc- Gen.~**  **(P:t~~':t** Rin£5pot Vin.t$ Coot Protein

**Ci~nc)** in X 17-2 P:lpayn mcxts lhc.: n:gul.:uory stanc.brd umkr the:

**ft..-dcr.lllnS~."Ctidd C'.**  Fungicide. nnd Roden1ieidc Ael (FI FIV\ ). , \fi<r rcvicwins submillcd :md publically "' niloblc dati :md in(ormalion.thc EPt\ concludes that the usc of the PIP P:tpay3 Rin gspot VIrus

**Rcsisllll1c~** Gene (1 1 Jp3yn Ring.spot Vim s Co;u Protdn G-:nc) in X 17·2 P opayt l will not c-ous-: nny un11:ason;1bk

**od\'C~l' dll--ct~**  on th e cn\'ironmcnt. I WA n l so concludes that the npplicnnt wns not

**1'\.~u ir**  **cd** 10 sub mit n pe t ition for n tolcrnn cc or n n cscmpt ion f fom 1he rl..'-luircm..:nt of t1 tolcmncc for re sidue-s of 

### t h ..:

**:~c ti\'c**  ingredien t on food cn"' J -.s. Specifically. th e OC\\ ' uc ti\ ' C' in grcd i..:nt is CO\ ' CI'\.'<1 by the

**cxbtin~ ~~:ncric**  tolcrnn cc exemption (40 CFR Part 174.515) for 

### par:1yu rin11-:,pot \'iru.'\ coot pro1cin and PIP nucleic

**~cids** (40 CFR Pan 174.507) and !here i s o rc:ISOnablc ccnain1y 1h m no hann

**,~,;11** rcsull to the U.S. population from

**3~greg:uc** exposure to rrsiduc s o f nucleic adds and the papaya ringspot coot protein from the XI?<! Pnp.1.yo PH' . Thcrdon:.thc F..PA i s proposing 10 gmnt the uncoodiliOml registr.nion of the nc'" ' acti\ " C ingn.-dient

**P3p3~'U** Rinp,-pot Virus Ro si51 orn:e Gene (1':11"')"' Rinj;.!pot Virus Cool Prolcin Gene) in X 17·2 l'nl"'l"' under FIFRA :.«lion 3(c)(5). The ri s k assessme nt s suppOning thi s proposed dccision cnn be found in the ru;S()(;iatcd n:gularory dockt:t (scnrc h for ··EPA·HQ ·O PI• ·2 01 S-0 4 t 8 .. a t

**hun ll**  **ww l&**  **', rt•s:ulutkwt~m·).**  

### 7. References Ura\ · crman. M . . W . P . **Barney.~ .**  D. Coleman. 2014.

**Nont:tr~ct iw:rs**  fbr Xl7·1 Line or

**tr~ns:genic** P3p.l) "l R ing:\por ·R Cfisuna PJ.paya . 1\on
- publisht..-d n:pon submitt ed 10 the t \gcncy. MRID 494932..0) . Bra\"crman.

**~1..** 

### \\', P . **0;1m-:~.** K . L>. Colcm::m. 2014. Group A·product nna.l>sis test g uidelines. Non-publ i s hed r<l)()l1 >ub mill<'<i 10 lhe Agency. MRID 494932·01 Coleman. K . :

**Bnt\'~nuan,** M.: Uam-:y. W. (2014) Group A ·l}rl)duct Ann l y sis Te.st Guide lin es: 

### X 14· 2 Line o r Tron .sgc nic l'apaya Ri ngspot·Rc s i s t nnt P;apnyn. J:trojcct N um ber: OS37U. Unpub l ished s tud y prepared by 

### lrm:rrcgion .a1

**H. es~:trc**  **h** f•r ojcc t No.4 . 726p. Dnvis. 

### to.t J. nnd 

### Z.. Ying . 200J. Dc\'dopm cnt of p.'lp;tyll bn: .. -Ji n g lines \\ith

**trans~;cnic**

**rc ~"tancc**  to Papaya

**rin~s:po1 \'iru.~.**  l'lant 

### Dis. 88:352-358 . E

. P:-\. 2007. CoJt Protein

**ofJ ap:t~a**  Ringspol Virus and the G .. ·nctic

**~t:ucri:tl** Necessary for its l)roduction: Exemption from the Rcquil'\.-.,tcrlt of:. To!crnncc. 72 FR 20434.20-135. EPr \-S t \P . Fcbru:uy -l. 2000 . Cl'unKicriz:.1 tion and non·lnf};<t orgnnism dab n:quin;mc-nts fOr protein

**plant·pr:5ticidc .**  SAP Kcpon No. 99·06:\ for FIFRA Scienti fic Ad\ · i.sory Panel

**~h.-c ing**  held IA--ccmber 8, 1 999. held ot d1c Sheraton Crysta l C ity lloh:l. r \rlingtOn. VA EI ' J\·S AP. December 27, 200-'. I ssues associated n i th dcpfc,ymcnt ofn type of plant· inc orporn tcd pr o tcctnnt (P IP ). !!-pl'Ciiically those based on plnnt ' ' iml cont protci i \S (I)VCP· Pll ' s). SA P Report No . 2004·09 for FIFiv\ Scionlific Ad visory Pnncl Mecling held on Octobc:r 1 3 ·1 5.

**2~** tl t the ll o l iday Inn
- Nn t ionnl Airpon. ArlinJ;ton. VA . Page 12 of 14

### E P ; \
- SAP. February 28 . 2006. 

### A set**of~c i~nt** **lic** 

### i ssues being**con sid** **c~d** by 

### 1 he E n\' i r on mcnt al Prote-c t io n Age n cy**~ga di** **g:** 

### Pl ont - incorporJ h ."d p ro tt '(;1llJl t s**bas ~."d**  on 

### \'iru s coat p ro tdn genes: Sdcntc i ssues associated \ \ i th 

### the proposed ru l e . SAl) Re po rt No. 2006 .. 1 tbr F IFRA Scie nt ific ; \ d\· i so r y J)an cl**rvtc~ti g** **h~ d**  

### o n l>s!ecm b..! r 6
- l\. 2005 at t he ll o l idny Inn - N:u ion:t l A ir

po rt . A r li n gt

o n . V:\. EPA 1997. Coat l)rotcin of Pap::t ya Ri ngspo t Viru.o; an d**~** 

### ( i clh:'t i c**Mat~rial** 

### Necessary t Or i L<; Prod u ctio n : Exemp t ion From t he R cqu irc m t:nt of a Tol<:mn tc. 62 FR .J 4572 -4.J 575. E P A. 2013 . R NA i 

### Tec h no l ogy 

### as n P es t icide: P r o b lem Fo rmu l: 11 ion 

### fo r I 

### lum:tn I h :-a lth n n d 

### E

<

ologicn l Ri sk Assessme n t. S u bm i tted t o the F IFRA Science A d v i sory Panel 29 Oc t ober 20 1 3. Do cket ID:**I'A-II 1'P-** **20 3~J.lS5.**  

### Fedcm l R eg i s ter. 40 

### CF R Pan 180 fOPI' -300538: FRL-5739-4 ) Coat prote i n of Pnpa ya R

i ns.spot Virus n n d t he**(icn~tic Mn** **~r inl** **Ncec s~** **·** lbr 

### i L<; l 'roduct io n: Exemptio n fro m th e R

cq u ire n1cnt of 

### a To l e rance:.**t\ ~u::;:t**  

### 22. 1 997. Fcm t i n . G .**nl..2011.** 

### A llcr£.cnici t y Assessmen t of1h c: P ap :tyn R i n

gspo t Virus Co:t t Pr

o t

ei n Ex p r e ssed i n Tr :utsgcn i c Rai nbow Pnpaya. J. 

### Agric. Food C h cm . Vol 59 : I 0006
- 1 00 1 2. Fire . A.. Xu. S .. Montgom ery. M. K.. Kostns . S.c\.. Dri\'<r, S.J.:. and Mello. C.C. ( 1 998) P

o len t and s rx--cific i nterf ere nce by doub l c ·s trn n dcd RNA i n Cat • norhab f

!J'ti s**.~I.. J:m:.,** **.** 

### l"n turc 39 1 :806·8 11.**Go t~** **\'~s,** 1> . 

### 1 998. Con tr o l o f l 'op3ya R i n

g$pot V i rus inl ' o paya. An n . Rc. \'. Phyto)Xlt h .. Vo l . 36:4 1 5
- 137. Gon,sa l \' CS , D . • Su1.uk i. J .• 

### Trip:nhi. S . . & 

### ferre i ra. S. 

### (2009). Pnpaya . Co m jJt·ndium of Trtm S

J.:t ' nic Crop Plmu s. 

### l..inbo. J. t\. 

### nm t l)oughcrty . W.G. 1992. 1 ) :tt hogcn-dcri\'cd r .: s i s t ancc to a pol)'\' iru s : Immune :md resis tan c e p hcno t y

p.: s i n transgen i c tobacco c:<p r c:ssi n g nlt ered fom t s of a JXHp •im s 

### t:Ont pro t ein n uc k o t i dc**~o."<JU il** **CC .**  

### M ole-c ul ar Plant·f'-·tic r obc lntcmc l . 5: 1.44· 1 ; 3 , 

### Lin . Jl si n· T a ng : Yc1l. (iow.Chin: Huan g . Ti n g·Tzu : Chan . Lit · F u ; Ch en g. Yi ng·Huc.y: \Vu. J hao l- Huc:i; Ych. Shyi
- Do n g; Wan g . Sheng· Yang : L iao. J i un n- Wang. ( 2013 ). 

### T ox icity Asse ss ment of Transge n ic Pupaya Ri n g:,.,,t Viru $ o f 8 13-2210 

### Li n e P n

payu F ruit s . .lourm1/ o/Axrku lturu l & Food C lh !mi :a

ry . 

### 6 1 (7). 1 585 -1 596. NC B I: BLAST . 2015. http : i lb l osl. n cb i .n l m . n i b . Sl"'ill l n.< L RID: J\VK5SVEX 113 . ( Acce ss ed 4 / 1 5120 

### I 5). 

### OECD. 2005. Consensus Document o n th e Bio loJ;y o f P:'lp::ty n (Caric·a pa paya). 

### Pagt! L1 of 14USD , \-APHIS. 2009 . .. 

### l,etilions ofNorut"gulmed Sutus 

### Gr.:u11cd or 

### Pc:I'Miing

**b~ ·**  Al•HIS:· 1 -=rom http :// w,, · w , ;.Mj< . ugl o u:<w Jbr¥ oot R"g . html (:Jcces.sed 

### Nowmbc r 2014). 

### USDt \. 2009. In response to Univcn.ily of Florid::t Pet i ti o n 04·337·0 I P St-e kin g a dctcm 1inal ion

**ofNonr..:~ul:l.h.'\1** 

### S1atus for X 1 7 · 2 Papn yn Re sistant t o J>npayn RingSJ)Ol Vim s. OE.CD Uniq u e ldentiiicr UFL-X 17 CP -6. Anim:tl and ( l (

:mt 1 h:.11th 

### In s pection Service. B iotechno l ogy Rt:l;Uintory Services. 

### Tnr.mlino. L. 

### M. (2008. l)<e<mbcr) . Consullalion ltll<r 

### h y FilA o n X 1 7·2 l'apaya . Food and Dru g Administration .

**\V~«nq:.ger.** M .. and 1' . J'ICii ss itr . 1998. t\ model tOr

**~~A·mcdi ntd**  QC'tlC' s ilencing in higher plruliS. Plrun

**~lolecul:>t** Biolllj;y J7: H9 · 362. 

### Yin g. Z .. Yu . X .• :md 

### 03\iS. ;\'1, J. 

### 1999. A new method for ob1 : 1ininb tran s genic pap:1ya pln.nts by Agrohuctalum·mcdi:ucd 

### tmnsfonn:1tion ofsom:uic cmbi) ' 05 . Proc. Flo . rid::l Smtl! 

### 1
- l orl. Soc. 112:201· 205.

Page 14 

### of 14