Proposed Registration Decision for the New Active 

Ingredient Papaya Ringspot Virus Resistance Gene (Papaya 

Ringspot Virus Coat Protein Gene) in Xl7-2 Papaya 

(OECD Unique Identifier: UFL-Xl7CP-6) 

Appmntl t y: 

I 

ck E. ~ scngcr. ii)Ftor 

11ic~ dfJ)csticidc rogmms 

I> ate: 
I. Summary 

'lltis document announcrs th;lt the En\'ironmcntnl Protection ~cncy (I!I'A) has completed its 

inilhll C\'aluntion of the proposed new plant-im:orpOr:nOO pmti!C'taru (PIP) tlctlvc ingn:<lient 

l'nrx'ya Kingspot Virus Resistance O~nc (l'apayn Ring.spot Virus C~uJ:trotcin Gene) in X17-2 

f'upnyu and has ~:onclud cd th:u it meets the rcgulntory and nf~ty St:l.ndmds under the F,-d~rol 

Insecticide. Fungicide and Rodc:ruicidc Act (FIFRA). The :sgcncy is seeking public comment on 

its J)roposcd decision. 

Tile X 17·2 Papaya has bcrn desi~n~..'\1 to contain 3 papaya rinJ;5)X)t iru ~ coat protein gene which 

m:akc~ it rc:l!oisumt to p:t.~ya rin&SJ>OI vi~ .a ~thogenk plant ,; rus li"L:t1 in(c.-cLS Jl3P3.Y:l and is the 

lc~tdint; ('t:nt.SI! of p3p3yaloss in Florida. T~pic:.lly. a b...-~thy p.1J'.l~" pl:anl can !ouo•l\•c up to 20 

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

~(.·:US. 

t\Ocr n:vicwing uhmiu~d and publically 0\1Jiloblc tl:.ll!l nnd infomultion.thc EPA concluded t.tuu 

this O\!\\' actl\'c ingredient is cover\. '\I by the existing tokruncc exemption (40 CFR Pan I 74.5 l5) 

for coat protein of papaya rin~spot vint$ in or on all food conunoditic:; uw.J l'll' nucll.!'ic acids (40 

R l'nn 174.507) and the I' I£' P:1paya Ringspot Virus Resisumcc (icnc (l'opay;a Ring.spot Vinas 

Co~u Protein Gene) in X17-2 l'opaya will not c.ausc any unrcusonablc ttdvcrsc dli.'Cts to human 

hcalLh or on the environment. Tilcrc b~. the Agency is proposing to c~btcr the PIP product 

conuining the new ztctivc int,rcdicnt Ul~cr FIFRA section 3(c)(S) for usc in papaya. 

2. Bnckground 

ll:tJ!ul:uory 

On Nm·embcr 12. 2014. the U.S. Enviri.)OI'ncntoJ Proh.-ction t\gcnq· (EI·'A) rccci\·cd an 

npplit::•tion lbr registration fOr the new plant-incorpomted proh:clnnt (I'll') actiw ingt'\."llicnt 

Pnpnya Ringsp<n Virus R~sis ancl! Gene (Papaya Ring.spot Virus CC'I:tt IJrotcin (ie1\e) in X l7·2 

Jlupaya from the IR-4 Project on hchnlf of the Unl\'crsity of' Floridll's ln.stillltc:: of Food und 

A&ricultural Sciences (UF/IFAS). 11lc nprlicant wa.;; not required 10 submit 1.1 petition lOr a 

toler:tncc or nn exemption (rom the requirement of a tolcr.:mcc for residues of the aeth·c 

in&fC'dicnt on food crops l:x"'CBUSC the new :tctivc 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 in 1hc sumnury S.."Ciion abo,·c. 

In 2008. FDA indic:~tC'd th::U il t.;Kl no mor-e questions n.~3tding the r~formc:d Florid:! line of 

X l 7 • 2 ( hll p:/Jwww. fd:1 .. Cil\'IFOS'SJ/FQ$dSsls:ll\s: R¢'8.--:~rc h.iG f.l'l M ts!Sl! bm i !iSW O}'u5m I 55 5 69 .h 1m) 

und in 2009 the tronsfonm.'(l Florida line of X 17-2,\ns d<:'n:gulntt."\1 by USDA·APHIS 

CJ:wm;;//www.:tphis.usda.l!(W/hrstnnhi:;f0S'!02/04 ~~ 70 l p CCim.pd r nnd 

llll pS;i/\\" w .o oh is. usda. sov!l! lll!f~ILi Sl\' riP R S 1009090 I. pdf.) 

X17-2 Floridian Papaya PI I' 

PoJXtya (Corira poJNIJ'tll..) belongs to t>lant tamily Cruic:occ lc und ~ a po1y[!_wnous hcrb:tccous 

p:n:nnial plant. There arc m~ny ditrcl'\:nt t.:ulth·::u-s of pap.:sy;a grown. Pur-1~'U ringspot \'irus is a 

!'agel of I~ 
pathogenic plant \'irus th::u infects p.1p3)'fl. The \'nrious strains of )Xlpay:a ringspOt vinas im)X'ct 

the- numerous p:.paya cuhi\'ars diOCrcnt · For example. the Hawaiian papaya cultiwus that arc 

resistant to papaya ring,_-.pot virus. c\'alu;lh."d by EPt\ in the 1997. and grO\\TI in Hawaii arc not 

resistant to the pap:ayn ringSpOt \'irus found in Florida. Papaya ringspot \'irus is the leading cause 

ofp.:~.p:aynloss in Florida. Typically. n henlthy pap::tya plant can survi\'e up to 20 years: howe\'er. 

ifinlt"(:tc:d \\i th papaya ringspot virus. thm life span is reduced to 4-5 years. 

Tilf! Uniwrsity of Florida has dcsignC'd. the X 17-2 r•rtfX'Yrt line to contain rt papaya ring.spot \'iru.~ 

coat protein gene li-olll a Stmin of the virus found in Florida. The \'irus coat protein g<.·nc put into 

the X 17-2 Papaya makes it rcsistruu to the p.:~.p:.ya ringspot \'iruscs tbund in Florida by helping 

the: X I 7-2 P:ljXIya detect and degrade papaya ringspot \'irus coat protein RNAs via a process 

described below called RNA imcrfen:ncc. 

55-I lhwaiian l>ap:•ya l'll) 

The generic tolerance-exemption for residues of p-apaya ringspot virus coat protein Md the 

genetic material n .. 'Ces.sary for iL" Jll'"()tlucti(ln was (lriginlllly rcqui!Stt.'tl w SUJ'fKlrtthe Sfk .. --citic 

papaya ril1£.$pot virus coat protein found in tmnsgcnic Pa pay:~ line 55-l. now in commcrcinl 

pap:tyn lint:S grO\\n in Hawaii. The agency's conclusion for the tolerance exemption was based 

on 1) the doc-umcmed occurrence and long history of plunt vinascs in 1000 omJ fcc:d (including 

the papaya rings pot virus). 2) no findings of toxicity of plruu \'iruscs to mammals. and 3) no 

findings of num1mali:m pathogenicity fOr plant \irusc.s. 

Plnnt ~ Plomt VirW('S, :md Plant Virus Orf('nscs 

Plant \'irusc-s are dependent upon the plant to reproduce. Whe1t n \'irus iniL--cts a plant cdl. it uses 

the plam cdl's machinery (nucleic ocicls und proh:ins) to produce ml'lny copies of itsctt: Plant 

\'irusc-s annck plants: they do not cause illnc:ss in humans. Plant virus particles contain the \•iral 

geJlt)I11C: packaged in u protein co;ll culled the 1psid. The c-apsid plays mlllly roh:-.s i11 viral 

infection of the plant. including \irus auachmcnt to cells. entry into cells. rdcnsc of' the capsid 

contents into the cells. p.Jcka.£,ins of newly forme-d virol panicles. and ntO\'Cntcnt of the vims 

within d1e plant. 

At the time papaya was first gi ee~d to resist papaya ringspot \irus. the mcchonism of how 

the ,·irus coat protein gene provid<.'tl prot .. -ction against the \'irus wn.•:; not fully understood. Lntcr. 

it was discovered that protection agairut the \irus \\'ns pro"idcd by n type of gi!'ne silencing. now 

understood to be R1'JA intcrff:n:ncc or R.NAi. RNAi is rtnntural process that plants usc to protect 

thcmscl\'CS ag:1inst viruses by detecting and dcg.rnding virnl RNAs. ,\I though RNAi silencing. is a 

natur..tl defense m .. "'Cimnism common tO plants. pbnL"i do not h:l\'c dfecti\'c gene silencing 

protection against all \·iniSCs. Papaya docs not ha\'<: df.:ctiw RNAi protection against the }XJp:l)11 

ringspot \'iru..o; on its own. Agricultural scientists. howc\'cr. can mttkc ll~ of the naturnlly 

occurring process of RNAi to prO\'id~ n:s.istancc 10 plant \'iruscs by inscning tl i:()Ctt protein gene 

(ht p: //www ap!'nct.orglcdccnt nt opn illbo!icn~m uprJr:~.sc sl bnt iruscs nsnx}. This is what 

was done to protect papaya against the papaya ringspot "irus. R~o-"S nncc to the virus is pro,idcd 

by nn RNi\i gene silencing medl.nnism whcri!' p:lJ)3)':1 rinp,spot vints RNA ns.so<:i:ued with the 

virus coat protein is detected and dcgmdcd. No inf<.·c1i<tUS viru.; J)lr1icles nrc fOrmed from the 

trans~enic papaya. 
ndrrs ndin~:: Gene Silf ncing and RNAi 

W/rot is RNA? RNt\ (ribonucleic acid) works \\i th DNA (dco:<yribo1lucleic ad d) in all cells. 

DNA contains genes that nrc the uepri t~ tbr allli\'ing things. These bhu:prints eontajn the 

informntion c\'ery orgMism needs to grow and survive. RNA works \\ith genes to tum their 

blueprints into the physical 1Ctuures we see in I ivins things. like eye color. RNA is a very long 

hclix·sh:tpcd molecule thn.t looks like onc·h::~ f of a spiral Strtircasc. In some vintscs. ~; ud ing. the 

pn.pn.~ a ringspot \'irus. RNA nlso ct~ a.~> the blueprint instead of DNA. 

WIJy is RNA important? :\II living things ha\'c a genetic set ofinstnJctions that arc the building 

blocks of life. ·n tcsc instntctions need some wuy to mO\'C nround inside n plant cell. n perSOn. or 

3Jl animal to tell ~ch cdl how to )X'riOml its role correctly. t\ $pCci:tl type of RNA. c.alkd 

mc-sscngcr RN1\ (mRt'JA) SCI"\'C!' as both o copier machine and mr~ l scrviC:l.' for cells. This 

mRNA makes exact copies of gene information nrld ddi\·ers it.sclf (and the coded message it 

carries) to the pan of the edt that produces prolcins. 

To illustt:ltc this prO<:'css. imagine these simpliticd steps for manufacturing n. car: 

1. ·n1ere is n blueprint (DNA) that contnins 1he design (Genes) tOr a c.ar. 

2. A copier (mRNA) reproduces the blueprint and distributes it \'i:t couriers (mRNA) to the 

f:lCIOI")' (cell). 

3. Workers (riboSOillt'S) at the tbctory assemble the car. 

Wlwt i;, RNA lmufi·r~tU t' (RNAi) and how do, s;, worK? RNAi. or RNA interference, is a natural 

process used to control genes and gene expression. RNAi is ofte-n uSI.-d by Jiving things to co111rol 

how much of a protein is mudc. It stops c-:rtnin mRNAs from eomplctins their tasks. there ron: 

blockins. or controlling the production or a sp~ilic protein. RNAi is n routine gene "silencing" 

process thtu occurs in plants. animals, and humans alike. Plants usc RNt\i to protc:et thcmsel\'eS 

from plant viruses. Building olr of the esarnple above, when RNAi is used. the copier and the 

eoudcr a.rc disabled and cannot dd i\'cr the car blueprinl to the: fth!tOJ)'. Co t.~q cntly. no cars nrc 

produc'-oU. 

3. Evaluation 

In C\'alu.ating a pesticide registration application. the EI''A nsscsscs a \\ide: vnrk ty of studies nnd 

infonnation to detcm1inc the likelihood of :ld\ CrS~ e1lL"Cl" (i.e .. risk) from exposures assoeit1tcd 

with the proposed usc of the product. Risk tlSSCSSmc:nts nrc dl!\'elopcd to cvalumc how the 

compound might ::tOL-ct a \\~dc- rongc of non-tarset organisms, including humans and terre.strial 

and aquatic \\ildlife (plants und animals). 

BflSCd on thl!SC a.~~s~ nt . the EI)A C\'aJwncs tmd npprO\'i!S conditions tOr each pesticide 

product to ensure thot penni ned u"'c-s and S3fcty measures arc approprimc to mitig:ttl! aJlY 

potcnti:ll risk 

The human health antll.'nvironm.:ntal risk assessments (including :m c:nl.langc:rc:d Spt'cics 

assessment) supporting this dc:cision c-an be found in thc- rcgulatol)' dockc:t (Docket Number 

c i'A·H0·0PP·2015·IJ.I I 8). 

r•ogc f·~ 
3.1 Assrssrncnt of Risk to Human Hc:tlth 

In onlc:r to nsscs.s PIP's risk to human hca1Lh. th~ EPA g<:ncrally requires nllergcnicity nml 

toxicity d3ta/intbmlation. generally consisting of !Imino odd sequcm:c homology .:ompariSUnto> to 

kn0\'•11 aJicrgcns and oxin . heat st;tbility testing. an m:utc or.tl toxicity test at ma~innun ha? ... 'U'd 

dose. and on in t·itro digestion assay in a simulah."'<l gastric cn\'ironmcnt. 

In the c-ase of Papaya Kingspot Virus Resistance Gene (Pnpay;t Ringspot Virus Co:lt PrtHcin 

Gene) in X 17·2 Papaya. EPA also evaluated the similarity of X 17·2 Papaya to the 55·1 Papaya 

currently being c uhi\'atcd in Haw'3.ii in order to dc ten 1H.~ whether the cxi g tolcrJ.ncc 

exemption. broadly wriuen. but wriuen to support the 55·1 Papaya. could be considcn."dto ;;&lso 

apply to the X17·2 Papaya. 

A. Gent ric f'apaya Rings pol Viru!l Tolcrnnct Exemption 

ll1c: 1997 generic tolerance exemption for residues of p.:tp:t)':l ringspot virus coat protein and the 

genetic m.:ttcrial ne-cessary for its production wn.s: rt"qU~;.'Sted 10 suppOrt the SJR"Cilk p..1p:1ya 

ringspot ru.~c().1t protein found in tmnsgcnic Pnpaya line 55·1. EPA concluded that there is 

r.:3SOn3blc ccnninty that no h.ann ,,;n result to the U.S. pofmkuion from aggregate exposure to 

residues of pap:tyn ringS'pOI viml coat proteins produced in plants as pan of :t plunt-pc:Sticidc: 

(p)ant-incorporntcd protect:mt). This conclusion wa.o; based on 1) the documcmcd occurrence and 

long hb;tory of plant \'iruscs in food and feed (including the p:lp.'lya ringspot virus). 2) no reports 

in the scientilk litcr.uure of toxicity of plant viru.:c." to mrunmals. 3) no reportS in the scicmitk 

literature of mammalian p..'lthogcnicity for plan I viruses. nnd 4) DNA is common to all fomts o( 

pl:un {lnd nnimal life and no instances have b<:cn associated \\ith toxic d Tccts n:lu!t..-d tO the: 

consumption of DNA as a component of food. 

SubSc<)ucnt to EPA's tolerance exemption decision related to the Huw ian p:tpayu PIP. 

additional safety d:tta wa.~ published in the scientific literature th::n confirmed the original safety 

tinding in 1997. Fcm1in. i.'/ (1/, showed that that the: fl:awniitm PIP's coot protein docs not pose a 

risk of food allergy since I) biointOm1atics of the coat protein amino ucid .scquc:ncc: shO\\Cd no 

signilicant homology 10 knmmaHcrgc•'L'. 1) the coat protein is rapidly dcgr.adcd in simulntcd 

t;ttStric lluid and is not stable in simuhnc:d intestinal lluhJ . .3) the coal piOtcin is unstable to hc.at 

treatment. and 4) the Hawaiian PIP containing papaya has been cmcn for more than n decade 

with no noted adverse el1i.."CL'i. to human health. (Fcm1in. ct al. 2011) 

D. Pl:mt-lncoqwr .. lt.'tl Proh:chmt Nucleic Acid EJ:cm pt front Tol~rantc R.:quircmcnts 

The 2001 exemption from the requirement of u tolcrnncc: for :all plunt·incorpor.ttcd protcctt1tlt 

nucleic. ncids: r-..'Cogni7.L"ti that nucleic ncid.o; could not only code for nnd control the: production of 

pesticidal substances in pl:tntS .. but could also be the pesticidal substance themseh·cs. as is the 

case " i th anti·scnsc PIPs prote<.:ting plants from plant viruses (now U11dcrstood as doing so by 

RNt\i). EP .. \ concluded for anti·scnsc technology based l:mL- incorpor.at~;.-d protcctnnto; thJt both 

r'\!'siducs o f the aJHi·se•tsc RNA a11d the DNA encoding it were cxcmp1 from the requirement of a 

f'ogc 5 of I~ 
rokrnncc. The: conclusion dur th:u th,·n: is n.-ason;~blc c:cnnin1y ttur no harm ''ill ~~~ 10 1hc 

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 prorccw.nr \\"3S ba..~-d on 1) nutlcic tleids: :tre nonnl111y a component or food from 

plnnc.s. nnd 2) experience ''ith the cxtcnsi, ~ usc of food from plnnt::, indicott:s ad\'crsc cffcclS a~ 

""'likely. 

C. I Iuman Hu llh Risk Conclusion!! 

I. !;imll.:a.rity 10 the 55-I ltawa.il:tn l':ap:aya PIP and the Nmtun.lly Q('CUrTing P.ap:aya 

RinJ!'pol Coal Pnlltln 

lb.: llawaiion Pap:1ya PIP .00 lhc Florida Based X 17·2 Papoyo PIP on: >irnilar. lb.: cool 

rrotcin..~ a.re the S3l'llC structumlly nnd functionally. The Floridian nnd llawuiinn \'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 llnwaiiM tmnsgcnic (:Onstruct dOc."S not pror"-ct o~inst the Floridi:m 

p:.p:tya ringspol ,;ru:; s1n1in. To contirm similarity. EPA compnn:d tht: llowaiion popa.ya 

ringspot virus coat protein aminQ ucid SI.'\IUt:nce \·ia the Basic Loc-nl Al nl'fh:nt Search Tool 

(I) LAST) 10 its Floridian counlcrpnJt. This compurison dcmon..\lmlcd o 96% homology. The: 

minor vnriution in ::amino ncid sequence between the two str.ains is nt:gligible nnd could be 

t: it:d since the virus phenotypes vnry gcogrophicatly. The slii;]H mnino m:i\.1 ditlCrences do 

not indkotl! any sig_nilicant health issues n:ln11.-d 10 IOXicity or aHc-rgcnicity during consumption 

or other cs·p<>sures. 

,\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 (HI K stmin of popa}n rinppot \'irus:) wns reponed 10 be 99.n. •. 

2. Additional Oaltt Showin.: ~u Allctgcnicity Risk 

lliointbm1otics t\nnlysis: s:ubmilh.'<l by IR-4 dc-monstrnted that the X 17·2 line of p:1paya ringspot 

rt"Sistant p::ap:1ya docs not represent n S4.1Uft:i! of no\'cl potential allergenic proteins. No signilit:ant 

imi arity to MY kno\m allergenic proteins was l.lcmonstrolcd in nn Allcr~;c nc search. 

3. llurnan Hullh Risk Condu)iun 

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 § 174.515) and ch.o 

PIP nucleic acid cokrancc cxcmpcions (40 CFR § 174.507) appi)' co chc Florida based X 17-Z 

Papaya PIP. EPA b:>.<eS iL< findinss on: I) lhc dcmonscrut,-d similoricy of chc X 17·2 Papoy:r 

rini)Spot ' 'irus coat protein to both th~ llawaHnn pa~ya PIP pnp.1y:a rin~~po t coot protein :u1d the 

nntunJll)' occurring papayn rint;Spot '-irus :,~min II I K coot prmd n, 2) thnt plruHs can natumHy 

defend thcm.s<:lve.s from plalll viru~cs by using RN;\i gcn~: silencing nn..J :1gricultural scientists 

~.'tl this dt:fcnsc mechanism to mnkc vulnerable papaya rcsist:mtto the pupaya ringsJ'I'C)t viru.o;, 3) 

the ubiquity of plant viruses :md nuch:ic ocid.s in food \\ th no reponed odnrsc cfli-cts.. unU 4) 

the nddition.:a.l biolnfomutics da111 dcmonstr.llinb :a l:ack of no\'cl nllcrJ;cnic protein in the X 17<! 

P~p..1ya ring,spo1 co:u protein. 

Pas< 6 of 14 
For more infbm1ation on the humnn health risk assessment of Papaya Ringspot Virus Resistance 

G!!rlc (Pap~ yn Ring.spot Virus Coat Protein Genl!') i1t X11-2 Papaya. pl1!a$c sec the supponing 

d(}l:umcnt in the associated regulatory od~l!'t (~c::tn:'h tOr ~IWA-II OPI' 201 5-04 I 8" m 

lutn:lfln,,r.r,•gulmian\'.w). 

3.2 Assessment of Ecologirol Risk 

To assess risk to the cnvironnh:nt for PIPs, the EPr\ n:quin:snon-tnrgct orgnnism toxicity 

datalintOtnHition. gc:m.·mlly consisting of c:~'1i g \\i th birds: mammals: freshwater and 

marine/estuarine fish nnd inwnl!'bt:lh!'.'t non-target n. ~-c lS. including honey bcl!-5: non-l!lrgt:t 

plant..;: ::u1d soil rwcnc:bmtc~ . 

In addition co the toxicity d:un. other data nrc also (·onsidc:mJ n:garding the environmental 

persistence of PIPs. as well as the potential for ofl"·sitc movement (gene llow) and invn~ en css. 

t\. Hazar-d. Exposure and Risk to Tern•strial Organisms 

I. Non-T::tfl:C.'I Pl:mts 

For hazard evaluation of a plant·incorporatcd pcsticid:tl sub!\tance that is produced from a plant 

pathogl!'nic microorg:mism. the Ag..:ncy dc:termincs whether its usc prcdbposcs other non-tnrg:ct 

plants. and non-transgenic pap:tya to other dis ... '"a.*'eS or pt.""St.s th:lt might trigger adnrsc ct1Ccts. In 

:1ddition. the Agency dctcnnin e~ whether its usc may trigger potential t(lr otT-site mo\'cmcnt 

(gene tlow) and introgrcssion (inttOI.luction of genes) into non-tmnsgcnic. wild or .. lt:ml- papa~ a 

populations. 

The p.1paya rings pot virus is sp ... ·dtk 10 th...- p;JJXt)':J plant. In X 17·2 Jlllp.1)'3. resisuu1ce-to the 

p.ap.1y;1 rings pot \'ims is pro\'idcd by an RN:Ai gene silencing me-: han ism wh.:rt: papayn ringspot 

\'inLS RNA associated \\ith the \'irus coot protein is detected and dcgrnded. No infcttious \'iru~ 

Jl:lr1idcs arc fl1nm:d from thl!" transgenic p:..pa~ a and thl!' plant-incorporated pesticidal substance 

does not predispose non-target plants to other diseases or pests thnt might trigger nd,'er.;c l!' tl~cts. 

f urther, as described in the gene flow Sl"<:tiOI\ that I'OIIO\\'$, the risk of gene flow viu poJicn 

tmnsfcr from the X 17-2 plants resulting in hybridir ..ntion of sexually CQtl'lp:ttiblc wild rclati\'cs is 

\'cry unlikely in the Unit...--d States and it'\ tl!'rritories but esp...--cially in the proposed gL"'gr.tphic 

region or commercialir.ntion (Florida). 

2. Birds :md Mammals 

There is a long history of consumption of the plant "irus p:midc:s (i.e., papaya rings pot) in food 

by bird,.; and mrunmaJs. without c-au~i ~ dektl!'rious cll~ets or C\'idcncc of toxicity: \' rus.infi..~ctl!'d 

plants nrc p:trt of the !l\'i:tn nnd mt\mmalirm diet, and there have b...--cn no findings which indicmc 

th::tt plant ,·iruscs arc capable of rcplkation in m::tmmals or birl.ls. thus eliminating the possibility 

of i11fcction. Funhcnnore. infectious panicles are not fonncd from the transgenic JXIP.:l)':'t. which 

h:lS bcc:n modified \\ith the: portion oft he genome eodin~ fbr resis111nce to papaya rings-pot viru~ 

and subcomponents of the resistance gene. Since this gene is cxpn.-ss ... ·tl only within plant tissues. 

Pose 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.1nicles th:at could pass n:spir.:uory or dermal barriers :lJ'M1 

th~rcforc is not like.l~' to impact mamm;ds. birds or ins..."'C'lS th.1t SCf''< M a food sourt'C for birds. 

Girds and man1mnls: would be cxpo ~;.'d "' th\! X 17·2 P3p:~.ya Plr primarily Lhrough inscstion of 

cissu~.·s. seed or fruits oftnlns.gcnic Pnpaya X 17-2. or lh)lll prey that hnd in~t.:~lcd transgenic 

r:•r:ayn. Contact with these surf11CC.:' is not expected to c~u lt in signil1cnnt exposure. though Mal 

csposun:- muy occur incidentnlly thruuHh groom ins. The submilt(."(l do.tn nnd infom1ation arc 

suOicic:nt to conclude: that the X 11.:2: Papayu PIP i$ highly unlikely tu inf4.'Ct bird.~ or \\ild 

mnmm:•ls und cause od\'crsc cfl'lxts.. 

,\, Noo-Targrt l nsr-ct.s lncludint:; li · Bees 

Nonurgct. inscc:ls inc;luding ho~y lx"C'S could be ~JlOSc.-d to tr.ln.Sgenic p;lp:l)'a tissues which 

contain papaya ringspot irus coat protein through ingestion oftlSSI.K"'S. fruiu or pollen of 

nan~~cnic Papaya X 17·2. or from pn:y dtnl Md ingested trnns~cnic: pap:1ya. Dispersal n.nd 

mon:mcnt uftransscnic p.1payn tissucs (e.g .. primari · scro or rnsit) could r~.-sult from 

at;.ricuhumVhonicultural opcrotion.J (e.g .. pl;mting) nnd \\'(>3lhcr acth·ity (c·B·· hurricane-s. ttopical 

t\torms uprootins the paJXlYil tr\!·C) and nnimal disperssl ofp::u1i:sll~ ·con umcd fruit. llowcvcr. 

plunt vin~s are routinely ingc..sh:d by \'irtuall~· nil organisms when \'irus-inti."'i:tcd fruits and 

WQI.'tablcs arc consume:O. 

The "irus is spccitic to only the pap:tyo plant. nnd insects such :1S aphids. I\\'0-SJX)Ued spider 

rnit~.~s and p.1p..l~"3 fruit Oy arc not Qd,·.:rscly aflCctC'd by the c.spn.....~ion of the p..1paya ringspot 

vl~ c:oot pro::ein (USDJVAPHIS, 2009). lk~use no infi.'Ctious ponicl~ are fonned from the 

transgenic p;~JXtyn nnd the mode ofiJc·tion is spc'\7ificolly for 1!XprcS..'iin~; r~islancc through a gene 

silcncina; m"'"Chanisrn to p:tpaya ring,.pot ~irus. no ad,·crsc: c:IT"rxiS an: onticipali.-d to non·targct 

in.'io4:cts. includins llonc:y be-es. n:g.sntle~ of" the exposure. (EPr\. 1997: 13.P,\. 2007: 

US[)A/APIIIS. 2009). 

n. lluzard, Ex:posurt' ltntlltisk IO 1\IIU:ltic Organisms 

I . f" rrshw,u,ttr f Uh. ln' 'trfthnalt untf Esruarindr\l:lrinl' Anlnuel5 

No :•d\·crx e:Oi..'"CIS to aqwni~ orpnisms arc anlicip:ued tfon11hc X 17-2 P~paya PIP. bcc3u..~ no 

infl'Ciious panidc::s arc fonncd from the t.r;uugcnic pap;ayn nnd the mode of action is Spcc'itic:llly 

fur t:Xpf\.--ssing n.---sisaanc:c 1hrough a gene silcocing mechanism lo plp:l)'Oo ring.spol '"irus. a pl:ml 

ru~ ~-cili:c to p:l.J:Uya. funhcr.thc: producl i:.~ not intended for dir«l r.pplico.tion into cstuarinc 

or marine c:n\·ironmtnL" nnd cxposun; and risk 10 aqtt:tric nnimttls. in, c:ne:bro~h:::;;. and lish is no1 

C~JX-ctcd . 

2. Aquatic Planu 

The JlroJ>OSCd usc of Papnyn E\'t:nl X 17-2 is to control a ,·iml di e~M.". The pesticidal mode of 

:1ction is spccilically tbr cxprcs ... ing n:~i~tar1ce through a gene silcndnJ:; ntt.::·c1mnism 10 papaya 

~;t po t virus. a pl.:mt virus sp..--cilic to JXIPil)'3. The product is not imcndcd for dinxt opplictnion 

Pose 8 ofl~ 
into ~st ari nc or m:trine C'O\;roruncnts :md exposure tO uquutic plants is not expected. Therefore. 

~d c:rsc cnCcts to freshwate-r nlld marine: or cstuurinc plants arc not anticipated. 

C. ~ne f low 

F<.)r PIP registration actions. EI'A also U...'Sc.S.Scs the likel ihood and cni:cts of off·sitc movement 

(gene tlow) and introgn:.ssion (the introduction of genes from one specie-s into the gene pool of 

ru1othc:r species) from the PIP plant to sexually COillJ'l.1tiblc wild n:lati v~ (S<.:WR) in the US and 

its territories. Registmms 01'\.'. therc:t(m:. required to supply :t gene flow risk :1sscssmcnt th:n 

discus.scs the possibility of pollen now to comp:1tiblc plants and hybridi7 ..:uion. introgrcssion. and 

stable ri nc~; of the Pll) lrnit in the pl::mt. 

If EPt\ ·s risk analysis concludes dun u proposed PIP trait hJS the potential to confer :1 selective 

ndvn.nmgc 10 wild and fend relatives by pollen transfer leJding to hybridizntion1 introgrcssion. 

and stable inheritaJlce. then prO:lCtivc measures must be taken to mitigute identilk-d imJXtCIS upOn 

n:gistr:.tion of such a PIP. 

The applicant (UF/IFAS) ofl'ap:..yo E\'~nt Xl7-2 intends w rde:\SC this genetically modified 

p3p::tyn hybrid for commcrci:llization cxclusi\'dy in Florida. No closely n:ktted wild and fer.tl 

rdnti\'cs coexist in this gcogrnphic. region (USDA 2009). and risk from sene flow and 

introgrcssion is. therdOre, highly unlikdy. The d osest rehned rd:uive ~ the Mtluntnin p:1paya 

( Vascunc,•llt•a spp.). which is. ntuivc to Ccntml and South t\ cric 1 (USDA 2009). If cultivated 

p01payn (Curica fWJNl)'U L.) m:rc commcn:ialilcd in an area where the Mountain paJXI)'Ol speck'S 

co-occurred. the risk of hybridization from gene tlow would be low. This statement is supponcd 

by hybridi?.atiorl au.:rnpts bct\\ccn culti\'rtted and Mountain pap:.t)'<l S:pt•cies thlt htwc 13ik-d 10 

produce imergencric hybrid:> (OECD 2005). In nddition. the FIFRA Scicntilic Advisory r anel 

(SAP) (2004. 2005) concluded that papaya would not form a ,;able hybrid " ith wild rclntivcs in 

the U.S. and its territories. 

BPPD concludes lim the risk of gene Row via pollen transfer from the PIP X17-2 plnnls 

resulting in hyhridintion of :a SCWR is \'cry unlikely in the United States and its territorie-s but 

esp.;.-ciolly in the proposed gcogmphic region of ommcn:i~l z: ion (Florida). 

A PIP plant expressing a protdn conl;:rring disease or pc:stn;sistnncc: h.as the pOtential to incur n 

compoc:titi\'C n~lva till)c O\'cr other r lant (ll:ci~$ with which it intcraclS and shares an en\' ironment 

(S:\ 1) 2QO..I). Therefore. as part of the rcgistrntion rc..-quest. CPA n:quires applicrutts to discuss the 

potc:ntia ll~'l r n Pll) pltuu tO coml!' in\'a.,ive in the environment. Typically. upplic;mlS MC also 

required to submit infonnation addressing the likelihood that a SCWR can become a weed if the 

transgcnc- i11trog,re.sscs. PIP pollen flow to SCWR has the potential to confer a selective 

advantage to wilU and ICtid n:hti\'eS ifhyhridi7a.tion. introgr.:ssion. :utd stublc inhcriumc.:c ::trc 

possible. 

The Uniw rsity of Florida demonstrated that there were no si~n c.ant diOi:rcnct:s in ph~no ogy 

between genetic-ally engineered X 17-2 l'apaya and non·gcnctically engineered C. pupuyu plnnt' 

P:age 9 of 14 
(IJSD,\. 2009). The l><k of d<C«Illblo significan<c in pl>nc ,·igc>r did noc >"Uppc>n cluc X1 7-2 

Jl.1p.1)-:J. would be \\'C'\."dic!:r in n.:nurc than it5 non-generically cnsincrn.-d counterpart. llxn:forc. 

OPPO concludes th..1t the likelihood lbr X 17-2 Pnp;tra co bc:com~ in\'Mh·c is low in the United 

Statt:s where ils commcn:inlinuion would be limitc.:d w Florida. 

llPPD l'i•rthc:r ~ond des since there is no c\•idcnce th.nt C. papaya hrtj wild or li!rnl relatives in 

the United Stotts and its 1crritory wilh which hybridization could occur. thnt nt tht: present time 

the conccn1 for the VCP tmnsgcnc to confer o. sclccti\'C odvlmlagc of invasiveness to SCWR in 

lhL~ Unilcll States is not 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 marinclestu;arinc animals :md insects. There: fore:. u "No Effe-ct .. 

dctcnnin:uion is m:tdc for dirC't'l and indirt.""CI ~11\"Cts to t\.~er:dl)' listed c:ndnnt;~rt.'<l. nnd thre:Jtcncd 

("lisH:d"J .species nnd for 1hcir designated criticu1 habit:l.t. 

F. Ecologic:lllll<k Cnnchulon 

·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 critic:.nl hnbit:tt from 

cx;po!iUn: to lhc Xl7-2 PttJU)'Il PIP. 

lk<ou;c of chc ubiquicous rucurc of plan! '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 gene tlow via pollen tntnsfcr !"rom the PIP X 17·2 pl.:mts fC$Uhing in hybridi7.ntion of 

n SCWR is \'«!t'Y wtlikcly in the Uniu:d States and ilS tc:rritoril.-s but ~specially in the proposed 

g~·ogmphic region of (;()mm~rcio i;o.J.ltio n (Florida), 

Sint:c then.! is no e\'idcncc th:tt ,KifK~J'U hu..-: wild or feral rei:Hi\'cS in the United St:lles :~nd its 

territory with \\hich hybridi7ation could QC'cur.th:n .tn thl! ptL"$Cnl timc tJu: concern for the vir.1l 

co:.t protein tra.nsgene to conti:r a sth.."Cliw udvomt.agc ofi0\1tSh·cnc:!'.S to SCWK in t.hc United 

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. Alter natives 

ll)' the: 1990s, papaya rings-pot vinlS hm.l n:ducc:d Hawaii's JX~pn~ n :~crcngc by 50'%. Titere nre no 

useful chemical controls. With the successful introduction of a r:.paya t•tr in the late 1990s.thc 

I lawai ian pnpayn industl)' cst~lllt.'tl nonnal production (Fcnnin. ct nl. 20 II). 

Page 10 c>f I~ 
Floritln's puyn industry has now only 300 acres. dO\\n from 500 acres in the early 1970s. 

Increased competition from othcl' countries. such ns Mexico. higher production costs (unit costs). 

and the lnck ofp.:tp:ayo. ring.Spot virus resistant cultivars h:.wc all played a role 

(http://c"li.-,jfias.un.edu/tC91·1 }, 

The rcgistmtion ofl'opnyo. Rin&SJX}t Virus Rcsist:mcc Gene (P;:apayu Rinl:!!l>Ol Virus Coot Protein 

Gene) in X 17-2 P:apayra would provide papaya ringspot virus disease rcsistam cult iv:~.rs of papaya 

in Florida and could result in cxp:mdcd production. 

5. llcncfits and Public Comments 

Dil)J'ICSticidcs arc pesticides dcriw:d from such natural materials as animals. plants. OOch:ri;t. and 

ccnuin minerals. PIPs. a cla.ss ofbiopcsticidcs. nre pl"Sticidal substrutcc.s that plants produce from 

genetic matcriol thnt h:LS tx"Cn :tddcd to the plant and m ay have the fOIIO\\ing bene tits: 

• Usually nrc inherently less harmful than con\'Cntional pt."":Sticidcs. 

• Gcncmlly :. m.~ct only the t:trgct pest and closely rd:ucd organbws.. in contmst h1 bro:td· 

),X."Ctrum conventional JX"'Sticidcs that may atlCct many ditTcrcnt organbws {e.g .. birds. 

in.~cts . and nt:lntmals). 

• Often arc cfli:ctivc in very small quantities and oflcn decompose tluickly. thereby 

rcsulling in lower '-'Xposurcs and largely avoiding the pollution problems that can tx: 

caused by conventional pcsticidC's. 

• Cnn g_rc:ul~· deen:asc the usc of conventional pesticides while crop yields n:mnin high. 

whcn u.<>cd a." n comf'(lncnt of intcgr.ucd pe-st nn:~gcmcnt prog.mms. 

• Cnn ofli:r unothcr tool for pest management in areas where cn,ironmcntul concerns limit 

the usc of conventional pesticides. 

In the F~.-dcm l Register of July 20.201 5 (80 FR 2802). the EPA announced n:cdpt of em 

application to register a pesticide product containing the new :u:tivc ingredient Papnya Ring.,·fH•I 

l'irtu' Rc.dJtmu·,· (;t•m• (l'apuyu Rh:s.)'pm Virus <.:out l'rmdn Gl'lll!) in.\'1 7-1 Papaya protein 

and opened n 30·day public comment period. The El):\ re,eh•cd two {2) comments to this 

publication. 01\C conuncmcr was n J).3p.:tya growcl' in South Florida and was in t:wor of EPA 

gr.mting the: rcgistrntion. Further. thil; commcnter indi c~t~ tlu:~t "ltJhis is the only opponunity 

that we ha,·c of being able to economically produce qu:tlity p.1p..'l)'O to tht! benefit of us as fanners 

and thl! t\ancrica11 Jt unt cl' '' II h3\'C a much bcucr product at a lower pricc ..... llH! othcl' 

comment came from two individuals from the Unh•en;ity of J!lorid:t. They too were in ravor of 

the rcgistmtion. 

6. l'ro1•oscd Regulatory· Decision 

The Om.ulxtSc for Pupaya Ring.spot Virus Rc.sist:lllCC' Ucnc (Papaya Rings pot Virus Co;tt Prott!in 

Gene) in X17-2 Pnpayn is-considered complete. The: proposed u!'c of Papaya Ringspot Virus 

Resistance Gene (Papaya Ringspot Virus Coat Protein Gene) in X 17-2 l'rtp:!)'3 is supported by 

this d:ttabase. In considering the a.•;,sC"sscd risk to human health und the cnvironmenL the EPA 

Pag< II o f 14 
conclude-s th;n P3p3~1l Ringspot 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~."CtiddC'. 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 Ringspot VIrus Rcsisllll1c~ Gene 

(11Jp3yn Ring.spot Vims Co;u Protdn G-:nc) in X 17·2 Popaytl will not c-ous-: nny un11:ason;1bk 

od\'C~l' dll--ct~ on the cn\'ironmcnt. IWA nlso concludes that the npplicnnt wns not 1'\.~uircd 10 

submit n petition for n tolcrnncc or nn cscmption ffom 1he rl..'-luircm..:nt of t1 tolcmncc for residue-s 

of th..: :~c ti\'c ingredient on food cn"'J-.s. Specifically. the OC\\' ucti\'C' ingrcdi..:nt is CO\' CI'\.'<1 by the 

cxbtin~ ~~:ncric tolcrnncc 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 is o rc:ISOnablc ccnain1y 1hm no 

hann ,~,;11 rcsull to the U.S. population from 3~greg:uc exposure to rrsiducs of nucleic adds and 

the papaya ringspot coot protein from the XI?<! Pnp.1.yo PH'. Thcrdon:.thc F..PA is proposing 10 

gmnt the uncoodiliOml registr.nion of the nc'"' acti\"C ingn.-dient P3p3~'U Rinp,-pot Virus 

Rosi51orn:e Gene (1':11"')"' Rinj;.!pot Virus Cool Prolcin Gene) in X 17·2 l'nl"'l"' under FIFRA 

:.«lion 3(c)(5). 

The risk assessments suppOning this proposed dccision cnn be found in the ru;S()(;iatcd n:gularory 

dockt:t (scnrch for ··EPA·HQ·OPI•·201 S-04 t 8 .. at hun llwwl&', 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 Ring:\por·RCfisuna PJ.paya. 1\on-publisht..-d n:pon submitted 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 

guidelines. Non-published r<l)()l1 >ubmill<'<i 10 lhe Agency. MRID 494932·01 

Coleman. K.: Bnt\'~nuan, M.: Uam-:y. W. (2014) Group A·l}rl)duct Annlysis Te.st 

Guidelines: X 14·2 Line orTron.sgcnic l'apaya Ringspot·Rcsistnnt P;apnyn. J:trojcct Number: 

OS37U. Unpublished study prepared by lrm:rrcgion.a1 H. es~:trc h f•rojcct No.4. 726p. 

Dnvis. to.t J. nnd Z.. Ying. 200J. Dc\'dopmcnt of p.'lp;tyll bn: .. -Jing 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\-St\P. Fcbru:uy -l. 2000. Cl'unKicriz:.1tion and non·lnf};<t orgnnism dab n:quin;mc-nts 

fOr protein plant·pr:5ticidc . SAP Kcpon No. 99·06:\ for FIFRA Scientific Ad\·i.sory Panel 

~h.-c ing held IA--ccmber 8, 1999. held ot d1c Sheraton Crystal City lloh:l. r\rlingtOn. VA 

EI'J\·SAP. December 27, 200-'. Issues associated ni th dcpfc,ymcnt ofn type of plant· 

incorporntcd protcctnnt (PIP). !!-pl'Ciiically those based on plnnt ''iml cont protcii\S (I)VCP· 

Pll's). SAP Report No. 2004·09 for FIFiv\ Scionlific Advisory Pnncl Mecling held on 

Octobc:r 13·1 5. 2~ tlt the lloliday Inn - Nntionnl Airpon. ArlinJ;ton. VA. 

Page 12 of 14 
EP;\-SAP. February 28. 2006. A set of~c i~nt lic issues being considc~d by 1he 

En\'ironmcntal Prote-ction Agency ~ga di g: Plont-incorporJh."d prott'(;1llJlts bas~."d on \'irus 

coat protdn genes: Sdcntc issues associated \\i th the proposed rule. SAl) Report No. 2006 .. 

1 tbr FIFRA Scientific ;\ d\·isory J)ancl rvtc~ti g h~ d on l>s!ecmb..!r 6-l\. 2005 at the llolidny 

Inn - N:uion:tl Airport. Arlington. V:\. 

EPA 1997. Coat l)rotcin of Pap::tya Ringspot Viru.o; and ~ (iclh:'tic Mat~rial Necessary tOr 

iL<; Production: Exemption From the Rcquircmt:nt of a Tol<:mntc. 62 FR .J4572-4.J575. 

EPA. 2013. RNAi Technology as n Pesticide: Problem Formul:11ion for I lum:tn I h:-alth nnd 

E<ologicnl Risk Assessment. Submitted to the FIFRA Science Advisory Panel 29 October 

2013. Docket ID: I'A-II 1'P-20 3~J.lS5. 

Fedcml Register. 40 CFR Pan 180 fOPI'-300538: FRL-5739-4 ) Coat protein of Pnpaya 

Rins.spot Virus nnd the (icn~tic Mn ~rinl Ncecs~· lbr iL<; l'roduction: Exemption from the 

Rcquiren1cnt of a Tolerance:. t\ ~u::;:t 22. 1997. 

Fcmtin. G. nl..2011. Allcr£.cnicity Assessment of1hc: Pap:tyn Ringspot Virus Co:tt 

Protein Expressed in Tr:utsgcnic Rainbow Pnpaya. J. Agric. Food Chcm. Vol 59: I 0006-

10012. 

Fire. A .. Xu. S .. Montgomery. M.K .. Kostns. S.c\.. Dri\'<r, S.J.:. and Mello. C.C. (1998) 

Polent and srx--cific interference by doublc·strnndcd RNA in Cat•norhabf!J'tis .~I..J:m:., . 

l"nturc 391 :806·811. 

Go t~ \'~s, 1>. 1998. Control of l'op3ya Ring$pot Virus inl'opaya. Ann. Rc.\'. Phyto)Xlth .. 

Vol. 36:415-137. 

Gon,sal\'CS, D .• Su1.uki. J .• Trip:nhi. S .. & ferreira. S. (2009). Pnpaya. ComjJt·ndium of 

TrtmSJ.:t'nic Crop Plmus. 

l..inbo. J.t\. nmt l)oughcrty. W.G. 1992. 1):tthogcn-dcri\'cd r.:sistancc to a pol)'\'irus: 

Immune :md resistance phcnotyp.:s in transgenic tobacco c:<prc:ssing nltered fomts of a 

JXHp•ims t:Ont protein nuckotidc ~o."<JU il CC. Mole-cular Plant·f'-·ticrobc lntcmcl. 5: 1.44·1 ; 3, 

Lin. Jlsin·Tang: Yc1l. (iow.Chin: Huang. Ting·Tzu: Chan. Lit·Fu; Cheng. Ying·Huc.y: \Vu. 

Jhaol-Huc:i; Ych. Shyi-Dong; Wang. Sheng· Yang: Liao. Jiunn-Wang. (2013). Toxicity 

Assessment of Transgenic Pupaya Ring:,.,,t Viru$ of 813-2210 Line Pnpayu Fruits . .lourm1/ 

o/Axrkulturul & Food Clh!mi:ary. 61(7). 1585-1 596. 

NCB I: BLAST. 2015. http:ilblosl.ncbi.nlm.nib.Sl"'illln.<L RID: J\VK5SVEX 113. 

(Accessed 4/ 15120 I 5). 

OECD. 2005. Consensus Document on the BioloJ;y of P:'lp::tyn (Caric·a papaya). 

Pagt! L1 of 14 
USD,\-APHIS. 2009 . .. l,etilions ofNorut"gulmed Sutus Gr.:u11cd or Pc:I'Miing b~· Al•HIS:· 

1-=rom http://w,,·w,;.Mj<.uglou:<wJbr¥oot R"g.html (:Jcces.sed Nowmbcr 2014). 

USDt\. 2009. In response to Univcn.ily of Florid::t Petition 04·337·0 I P St-eking a 

dctcm1inalion ofNonr..:~ul:l.h.'\1 S1atus for X 17·2 Papnyn Resistant to J>npayn RingSJ)Ol 

Vims. OE.CD Unique ldentiiicr UFL-X17CP-6. Anim:tl and (l(:mt 1 h:.11th Inspection 

Service. Biotechnology Rt:l;Uintory Services. 

Tnr.mlino. L. M. (2008. l)<e<mbcr). Consullalion ltll<r hy FilA on X17·2 l'apaya. Food 

and Drug Administration. 

\V~«nq:.ger. M .. and 1'. J'ICiissitr. 1998. t\ model tOr ~~A·mcdi ntd QC'tlC' silencing 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 transgenic pap:1ya 

pln.nts by Agrohuctalum·mcdi:ucd tmnsfonn:1tion ofsom:uic cmbi)'05. Proc. Flo.rid::l Smtl! 

1-lorl. Soc. 112:201·205. 

Page 14 of 14