16

Genetically Modified Foods: [Potential Human Health Eff,ects

A P, ." '" 1 '" :5· B· 'd:l. '.11 d S' 'W" '.' B" E· 2

.u sztalll, "., ,a r ,,Dez ,a 11 .. '" .., wen

'formerly of The RoweU Research Ins!itute, AbenJeefl. UK; 1,Departmeflt of Pathology. University of Aberdeen" ,fonesterhiJi. Abel"deen" UK

Ilfltmdudiion

The :scope of 'thii:s review is restricted 'to data-based. consideration.s :llibou'~ the SSifety of g.eneliicalIy ])B!OdU]ed (GM) foods of pEant oeigU.TllO-f healtlr, No opiniens unless supported by exre·rimentai results will be discussed .. The emphasis vrl1] be' on p.llipe·rs pllllMisJrred in peer-reviewed jnumals, A few articles will be mentioued from non-peer-reviewed journals but only !if ,they i1nfi1uenced! the development of science-based ideas for the reguill.allcory p:rocess. Elnri[[onmen1lcal Issues will nat be dealt with.

Safety evaluatlon OF wholef,ooos deri.Y,ed ,tmm. crops wiit~'1 considerable natural variaWliity is more dJifJ!:kllllh than tm~ of a s~ngle dnelTIllica1, pharmaceutical or foodadditive, ,m" defined mixtures of Ithem .. Published results o,j tests fOol." toxicity and numil:Ional wholesomeness of oomples foodsrnffs are therefm'e .{ew and far between, A recent comment in Science described 'this in its 'tide: 'Hea~th risks of g'e:netiica'[iy medlfled .foods: many epinlons ibut few-data' {Dom]fIr,go, 2000). Even a ,eursory look at the FiS!~ of references efa .If'ffeJ!lt maj':orr review 01] food saf,e'ty ]SSllLeS O<l!lIirpe~~ et al., 3001.) showed. tha:t mast of the publications referred to ... 'ere nen-peee-reviewed institutional opinions or envisaged rurure sden'ti:Hc

.' E-mail: A-Pusztai,@freeU"U!t£o_lIk

and nnetilnodologkail de\'e1opnilents for sa~e'lly assessments, but were short on actual pubIlished scientific pape['s on which a t-eJiia'b]e database of saf,ety could be' founded. JlLr.dgmg by ,thea:ruenoe· of published da'l:ai in peel'reviewed scie.nt.mc lh:eratm·e,a!ppi1.re:[]I:~ly no human clinlcel trialswifh GM food have ever beenconducted, Most" alttemp'lr£ro establish the' safety of GM food have been. indieeet, At best, inferences have been drawn .. from animal Imals, but the preferred approach is to use eemposlfkmal eompansons between the GM food:stlliU and iits tredltional counterpart. If these results s.how no :si.gnmcant d .. ifle1~enceSt the hivo .~l)odS'tuJfs are 'subsltantiaUy egjuiv.a:llenf. me<m.mg: tll.lal~ ,the GMj:(md is as 8llife as the non-GM food. Thus; as the reg;u.laHOofI :is almost exdw;;ilvely dependent 011 'substantial equivalence', the published results of GM :food analyses and iinJerenoes drawn .from them for flea.llth willi be examined clitOCBiHy lin I~h.is review,

In g,enel:k modIfication. ,the iinl·ended gene ls ~floo:rpo:rilllred into the genOElll,e ofa ,crop l!lIS,in.g: ,a. vector 'Ql)ubinin,g several other geneS:. fu.dlLrdiIlg, as :lli miinlJJlllUm, viral promoi['.e~~"S, tra!£I1S00.ptiOJl. ~el'm,iFIa:to~B,i1,ntilb:iotiic resistanee marker ge:nesand reporter genes. Although in GM food safely the l"O]e' ofthe iin:iended. gene Is very impoetant, the poten'l:ial

CCAB fntErn.,},tiooal1003 .. faoo Safety: Cot1lamft1.1lrJlS aoo TOA'im (ed_ .~ .P. F, D'ME!lIo)

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·effe.cls ofthese other gelM."s needalso to be taken ir[]t~o account because oitthe:r ¥1i1:r~s ·01 tithe consteuctoe the inse~~1dion of Ilrllhe vedl:o:r could oonrttribUilte. s'lJioot:u:n.tiaJlly tothe .OVerllim. e:f.f:ed fEw·en end Pusztai, 1999.a). There lis iinf.ad oo]1l1l:e eli.]ia .. enee that soue of the other genes of the vector ]1I],ay hevean effooon Sillitety. Thisis pllii"1t:iciUla:r]y so as jj~ lis now .b,own tmt DNA. do.eslJlO'~always bresk doWI1l. in~hell.]iirrlentary b:-ad (:s.:tuubbe:r~ el ,Ill" 1:994, 1998; H:Oh.Uweg .and Ooeriller, 2001). This opens up '~he pos:sibi!Utythatthe antibiotic resistance rna.l'keJc ~iFl:et Ellilliddldkm to others, may be rmke:lll!l!p by baiGlterla lin the d:iigest]ve lrnd and. cOInmbute liothe spreadiintg oJ antlbi{)rIlc resistance Vla 1:nl!J!]!l1l:ang;u.tbadeda, In d:n.is ·conFex:t, one potenrt;l,Il]~y :i.mpodan;~ obseFVIli·~onwas lfha,t: a sub~~;l]![lItla~ PTOPo:rtiorn (6--25%) oJ Ili.gene:!:ica]]y efn;ginee:red. plasmid sl!l!rnved a l-ih eKpOSUl'e Ilo human Silli[h"a (MeFCe:r et ai., 1999). Padlii1]]y deg:radedl p]asli!lnid UNA also suC'/Dessfu]]y ir-ansJoI']1ll1ed :5l:reptococcIlS gord,outf, a bactemum that nOnl!ll,a.]]y lives in ·the human moult!. Sailliva also contains fadm's '",vrud:n i:nn'elJJ~e il!he i1b:ilty o.f hader-iia tobecome tl'aIlls:fm:m.ed. by nakeJ. ONA. The:reJme, the p~iO!loped~ of the up~ke of undegraded o:r pa:rH3J~~y degraded vedor genes, mdudfu:g ih.eal1hb:i·otic resistanee gen.e, MIl have ·wbe seriDUS~y considen~d" .Ho'we'v.er, the maineoncem m. GM. .tood safe~ lis what 3J.H!' the direG~ e:.~Jects O'E ·t!he e%pMssion of i'he main. i.ntte.11.d!ed.genea:~~elc Hsi.DB-ed:±o:ni illi.to t!he p]an;t geiFI:ome via a gene COJ1striLId. Am. addi.monalaolJtce:rn. 'is ~m~ 'ithlS may also cause s.ign.:ifi:caFll~ indirectand l!l!IJt» ~ended effects .oFl tlrte eKpress:ion andfunctienairy of ~he p~ailllJr s OWiFI genes. 'fine Il!umbe:r of: copies ohh.econstructilFl!~'t?I'~edllind :theiij" Ioeation iiil!lJtbie p]anlt gelJlOme (p]erolropkeffed) are of p8.[t±CulaIC irmpcdalll:ce irrn thisrespect, mrtth. ~ihe poss.ib:ilty t~a~ ]1I1I:a~~: .un~~eded .changes rna!}' oecur, Th.]S poss.]biilhty :I.S l!ili.flJJCt

@eiFI:er-aUy accepted, Ilindthe iJfIllJJcl!equacyof: the currently used methods to de~.ectthem is hequeFIt]y ad:rnow]oo,goo (KuireF e~ ,Ill" WOO).P~.e~.ot~iopk eUeets ahvays OC'Cl!l!iiml~.h. bott! conve.nmOFli1] ulosis-breeding and genetic engineering, and :~.he:i:r unwanted ermsequeiFI:cps l!]suaUy are e.ljjmjlFl!a!~ed by emriirkaUy se]edinJg krr ~~'te desired t:rait and discl}Ming lh.epot'eIlltidy haemful ones. SO]]ll·eo~ these .changes are unp~ieJidahle and. thereJm:e ... "e

can onTIy COmpa[ie the known properties and coFl8iIEi:tuen.ts butc!YI!n.O't look fm, or even Jess ani11ysetnntkno¥l'1li. ,comr0Ftelli:ls.. This l:Elll.pme8 ~im:itatuolliS on ou:r se]ect:ioncrHeria.,. Re]iiance based so.l.ely on chemica] a!Ilia~.y~is o.f Ii!In,acro/ ]]IllkwFlliLlh'rentsaFI:a known tm:hns 1SIli!: best i.nadegullrt.eand_ a:t.vo['st, allonge:.:ODS. More sopbtisHcated ana[yHca] methods need.t,o be devised, sl!]ch as mRNA .I]ngerprlirl!tmg. pl:'oteomksana. sec.onda:ry meitabom~e P['o,f.i]lng (Ku:iiper" et lilt, 1999}, However, Ilind. most :J.W:lporlant:llYi lhe~.\e 1S an l!]:rgen,t need. to devd.op comp:re.he:ll5i.ve tox:imEogka]fnu1trBio:nal meth.ods ·~o screen (m" liheurun~endea potefl!tla]~y de[·ete:ri01ls c:OFlsegjuencesfor human!anima~he,a],rlrl of g~e1tic manipn'bltioFl to IPl:npoErTtt the probJe.ms lint .ad.vllinae ()If~Jhe :incorporaittion of the GM. loodstuU init:o ~ihe .tooa. chaIn (E.WeFI a!I].d. P'l!JJsztai, 19990). A]1!ihough sOli!llle li:l1l11iled a!l]ili!ll;8J] il:esllts have been done, only a .few oJ these have beeFl pnMisb.ed. However, da,m hrom some of ~Jhese s~nd.ie.sl'ellJent~.y hi1ve been p]i1ced. ontheln~elIDeL Althol!]gih 1!ihey were no'~ pee:rl'ev:lewM. they were inceeporated inlio ~ihis['e'!Ti.ew because oJ th.ei.r po~ef1ttilJJ[ 1]l1~po:rli1nae :fm o·~e:r sdeili:ttists,

Non-~eer-IJ'\ev'~ewedi Sil'l~:etyl es:ful !IlIliII CO'.lillIIeIJ'lcii<lII CoM Crolps ~1i1I Urue Piulb!11ic I[)loma;liII

The·f.[['st example of official sllfetye·valua.tim:rus O,f a GM ·aop, CIli~geFte! sflAVR. SAVRllLI t;omaJtq indu.d.iJng: a 28-dlllyrnt feed.- 11F1g imal,.v.as ·conullisslJoned. by ClJ!]gene·~or the rood and Omg: AJEl1liruslrraifioFl (FDA) before its geneTa] release, A.HnoiLI.g'h the details of this ~t:udy have never beelFl published properly, because ~ms work had su.dltl an extr-:a.o:rdiFla.ri]y rnajp:reHecl and. 1rn:t1ueneed GM(ood l1eg:lLlill.aittion in the USA.aFId elsewhere, thereis a cornpeUiFlg need. boanalyse the methods used and t~le concluslnns real:hi.ed.fo:lllrn.natdy, as a result OlE Ili court case in I~he USA (A]~iance fur Bio-k1tegril~ e~ a[ vs, Sbala~.ael ai.), ]1Ilmt data. in the FDA's mes are now 0,0. Ithelnten:ruet lin the pub1±c

349

d.oma.ilFl and can It.herefore be evall!J!a:~ed (AiHa:ntce(ol'Biio-hll'legtity, 19918).

This GM tomaw shmcl!y shows ]!l~as1t o.f the prob~emswh.ich Nl~y beentC01liFl!terOO. in GM .food safety evall!J!a:t~.arT\, p:8lril:ioo.br'ty ii£..Hh the wmaw,lhey lJ!lCe &miiJts mtih.er Ih.asIJl food.stuns and thei:r p:ool.:eirlll and eiJIe:rgycon1te.nb lJ!['e mSl!J!f.licienl fal:' SUrp()]:'lting i[he gr1O'l\v~h of yO'lI.ngail!l!~mals. The me~h.ods l!J!sed a[1ld!l'esu.lb dbtailFted lin !:!his srudy l3JFe i.m:rol'~IJI~ Illa~ on]y (m~ Iltheir awn sake bll!][ also for ,their :i.nfll!J!eDae an the processof :(legu].artlon.

As 'suilstaFItfi.a] eql!J!ij1i.'a~,e[1lJ::e'(eatm'es so prorn~[1I.en1i]y irllI. GMfood :re.gu~ath:m {Ku)pel: et Ill" 2mH), including irllI. this GM tomato stl!J!dy, Ilrherei.s a need to ]ook ]!lllOOe dosdy l3Jl thiis concept. nus Issue has been aeal,twiililll in SOFlle' depth by a recent article ()d:mlsl.one et al." 1999) ]n whidll the pmMeNlllS.v:i:l;:h ~rns coneeptwere hi,ghl]ght.ed, such. asthat 'sulbstanfial ,eqlliivailelJLC'.e" has never beendelined properly and that~he:re aee E10 legdy b:[[1Idirng rules on hmv to estaMish it ]n practice,

DHle·rences lin growth COlJi.dl,DOnS cam have a serious :i~llpad olJloomros:ition <lind, th.e:refu,re~]ifI theab~[1I.ce,ofspecifk8JtiQn of the origin l3Jnd the ,ao[1ld]liions 'OfCI.drti.'Ila,t:ion of the different 'GM and [1I.on-GM SIllmrles, sh:ict sdeiJI:tl:fk: liJompa:ciso,ns cannot be F1l11lide. These' l3I~e nol!va]id 'uIJJessthe parrent ]i;[1Ie is grawn side by ~tdemJtr;h. the 'GM ]li[1l.e .. C'ampiu:isOIJlS w:i.t!hrus~O[·±CllJ] m·~:ile"a.ry values have oruly ]jj]!J!llit.ed !Scientific vaJ1cl:ity.

'S:ubswl!l!tn.a] eqll1Vl3JTI,e£1l.c.e' irs a C!l'-l!J!de, nonsd.e[1lt:i:fk:()O[1Iceptc It pmvidles a EooiPJlI.al.e~m: the GMhiotedtilJlOlogy cI}]!lllp:m.ies [1I.o't lito carry out DlutritrOFllllJ] amdt.ooci.co]ogka] ,animal:[es'1[s to est;ll!b]ish whether ,the hio.]ogicalefIect af the GMcrap-based~ood:mrlfi.s slibstll!l!l!t~a]lly equivalentto that of :its ncm-GM ml!l![1Iterpa.d. U~herefore allows rthe]Illl ita daim that thereis no. need fur hi.o]ogical res!li:ing because the GM crops are !l<i:mlll'ilar '1:0 ,their. ,ccm.ve:n;nonal COllI!FIltelvart- wh.ii~e on the ather hand, because they co.ntain novel genes .hnm other oI'g;llJTI!ism{s):, they are patentaMe,H:aweV'eT, l!J!m.ntentimlll3J] mlld. u.np[<edie~a!blechanges can occur in. p]ants beeause oJ the lnOO1'po:railion and posH:no[1l.ing of the v,ector m. [he p:~.:ll1Jt genom.e.])t: cannot

:t.he·reJo[<e bema1#!rn. wrnrlh ,of It.he h1J[oo:rOO:s Ol~ mmponeill'lts of :tthe GMcropma:y' ca.lTY tD!I;:rC oraneiEgen1:c p[<ope])nes, .ru most o'~ these al'!E'urilrno.lWifI, by dief.in.iitioiJI, they 'CllJTI!I1I.o'~ be ilFtcluded. :in l3JFIlllJ]yilti.cal oemparisons, Dete[ml.ma,D.oJ) .of ithe amOl!m'is oj pOO!~e[[1I, ca:r:bohyd.rnltes~f8JtsaFl!d other' Illumenil:sCllJifI on~:y he a s~a.di.ngpai.nili. The ~oFb!ll!J!mp'Iti.on of 1TII1Iinor l3Jlrtd l!l!l1I.e'xpeobecl cO[1lstimeTl!.ts ol~potell!t~,llJF~y high biological a:ctfiV]ty may have CIHl&icl!emMe and d:isp[\opo[-troFllllJI~:ely Fa.rge effec,[s on the diigestirvehcad.. Their. presence., ,therefolCe, ,can on~:y bel1e·vea.]ed&o]!l~ animel studies, 8J[1I.d. ,trus makesit irmpemil:ive ,tha:t these are perfun1lled'l\vHh l3J .[Ja:'I\vless des~:gn l3JiFLd ,eI(pe["imenta~olJi..

The .lFLAVR SAVRTloII 'i·ornate> wasp.md.1ITaed by 'lIiIl!.til.sense' GM. '~edJil"lo~.ogy·. As pad o'~ ]Is safelyeva[umlEiion, i'~ was sl!J!bjooted ,to compositlenal analysis for to~] pw~eiiJI~ v:iltairnilFlsand mi:nt.eTlli]s to estabhshwhether any unexpectedchanges in gJ'oss HuH liJompo:;cHiou had. arisen as a resuh o'~ ~ihe ]~l!leg:ratiolJl o'~ ,theflAVR SAVRCfM and! ian" genes into Ithe '~omalo gelllome.])t was claimed iltuar~l]o signiificantchangeswe[je .knwlJld and dm.t the iJOrntel!l!ls of pa~ellll]aUy ~oxk glyooa~.k,doiid!S, pa.r.ti.cu]a:rly '~om,llJtme, and. to alesser exj[e[1l:~ 8O~al!l!ine and ,ch<3ooru!Fle,weTe also slmflar (Redenbaugh e~ ,al., 1992) ,andllihereJm.'e tl:Jt]s GM tOIITUitD was sl!J!bstamt:iiaUy ,equirva~.!mt :to olll.he:r FtaIJt-GM~oma~ol.iilll:es .. Bowev,eT, to supp~,e;me:llit these, sev,ernl(eed'ing studies were also rerkwrned by oJnliF.lJtercia~.~aboraloriesat the req1ITest Qlf tl:!i.eFDA..

First:. mntge-Md:ingJ li]TIllitacute oral. toxicity 'tests of the praaessed ~O]!lllatoesinra:ls w·ere carried out by the I!1TResel1och[m'l:iitu1:e o.hhe ute Sciences Diep:8lrtmeiJI~ (Ch:icago, Hilinoii5, LISA). A sirng~e dose of thehomogenates PICepared &oma:bout ,so g of various GM l3Jnd. iJ(m;l[io] roma:kles,['espectbldy, w:asacl!Nlllims>I~ed 05 ml lk:g-l) by gavag·e ~ogro.ll]rS Ol~ Harl:81[11. Sprague-Dawley :rats (live male or fe.male[ca~ per gl<OllFp) fed {fa Ub,ittmi:onral1 chaw for 14 dl1Ys ~o ,es~a!bl]sh.¥h.eth.er ,the GM tomstees were roxie .or n.olt As cladmed, no '~es~ sl!l!bstance-re.lated. mortaliities iX'.C1!l!n:ed and iiJIcreas-esi:n ]!lllJean body weii~hts were noitt

350

~iigIl!~JiC'Jm:t1y diitlel!eiElit between GM a.nd oonJt:ool gIDll!PS" Hiaweve:r, as the range 'oflt.he [;art:s' starling weights was unacrepttaHy wide (female rnlrswd;gh,oo 131-lliBli g (± ::I.8%) and male [-a:ts Th.59--2!).4, g {± 2'3%}j, :ill! smJIJ, a shmi (14 day) study wHh ,I]ve rats per glUlLI!P, itwol.lld ha,v,eDee:n d'HHcul!t lo[· si:gnmcalllJt d1.fferencest,o develop. For C'iO.lllIpa.risQn.. an.]y a few pe'[. cent Va[ia,DOFIJ in stadmgwd,gh:t:s is pe:l'TIlillHoo m rapers plLl!bllished lint highqua]ity' nuh:itimll1lJ] jOlLl!lr'FIll3J]s> "fl:ms, the POOF design of IIhis feedmg s'ru.diy hrg,dy nva]id.ai~oo,the concllLl!sioru.that 'GM tOli!llatoes 1OVe[ie not tDX:i,c" To slLl!pplerneFl!t thes-e, three more :rat feedings studies o,f si.milar. design 1OVel:'e carried out by :~t,.eITli1tianal Research alllJd D'e'VeFopment Cmpo:r.atiiQrn (Matcta'lov.alllJ, ~ch.iigan, USA).

.of the three studies, t[he ]1I1IJost mmp]eltte set or data ]S l3JvaihMe far the second. kiJ tlh:is, rolLIllc grou,ps of :rats {Wmales and 2'0 females pel' gral.lp) fecI slailllJda.TJJ['a,~chow lOF 2.8 days we"e gav3iged rnrke daUywirth. hO]1l~.og:eH2ed tom:~toes (15 m]kg-l). 1'w,o gID1lipsWe[ie glVeFI! GM '~om3itoes, CR3-613 or CR3-623 (CR3-623 'is the mrn.IDl1ten:lBi]FILAVR SAVR'TM ~omato), Therewere two O),ntroi] gwOlLIpS, one' of which was gava@ed with the pareFUt Or:! ~omato homogenates and . .a second o)'FI!tml g'il'DlLIp lnwhieh the r3ilswe1'e gavagedw:ilt'.h. 'v:l3Jter ev,efttholLl!gh. the relevance of this g'il'DlLIp iis somewhat CJjuestl.onaUe. AtlLhe request o.f Ca]gene, an exre])~ panel was [iemi.noo (El\.r\.i1RON COIf'" AdiI1lg~QIJl., Vi.[~ girua, lJSA) to evaluaeethe data. 'filley coneluded lhBl~gava,g:i.ngratsw:ilh GM~Qmato puree resulted in no. S]gni.l].cantt dhang:e;; In body weigh!\, k!OdoQlJIsl.lrnpHoFl! and. diu]cal ,cheJITlllistry or haema~o]ogy parameteD:s In o:ml!;parisQn with o:l.'llltrol to.ma:~oes. However, there was ,a Po.s81!b]e treablte[][t-re.la~ed lneresse iin glandula.. stemach erosio:rll/ IJleCW.SI.S iin four out of 20 female Fats but none in fhe eontrols 0[: in male rats ait the end o.f tiFte 28-da.y~e.edi.ng peried. The mneher of f:o'llIil' fenl.<I.Ie rats was jjncreaseG to sevenwhen lithe rus~oLo.g}' s]rdes!ioverete-scm~ed. by lP' A l[HGO,

ll!flt mdependent patho[,ogy'lo'¥,odl,jjng g[iOiU.P, This pw.mpt'ed a repeat stlLl!dy :iillli wh.kl:n. tirLe dose o.f rl:hetom:atD puree was ilFlcr-el]sed. by Mo..toM,. Unfodunate]y:. in 'lh.is study, SOlTIl]e o.f !!!he eR3 cenfreland C'R3--623 'GM tomato Jintes we'[ie g[iOWn a,! ,&iJfe:reIJl:~ ]oca,DOFl!S and ha.r.vested at dHlel:eFI!ttimes fro,m rtthose lint the second. experiment Hc.wev,eiF, 'lh.is w,as I]O~ regllroedas im;po])tarn:t by the expert pand even thOll]gih, when the same '~om.l3Jtoeswe:re used. 3iS lin. :tth.e !l-eao:nd. experiment, tihe ])esu],1ts appeared 'to show simiar 1!telJldencies; 'Mo. out o.f t'he 15 (emaJles deve]oped stoNl!llBi~h glaiEliduJarel<osi.ons wirt.h. tine GM roma:wes, whiill.e none We:ref01lIl;d ]!F1J tihe O)ntro] (eli!llales, Howeve.[·, in a :noit de.l3J:r]y I.ln.die!'sla:ndah~.e way,the~.mGN pane]aQlJlduded !!!hat the Jesi.on. o.J glandlLl!lar e[iOS1.0n w,as not :r.el.l3Jtoo. ,to ,the 3idJ1m.illlJis1trl3Jtion of: GM tOJ1l].aritoes.. Accord:ing to ,them, sl!lch. ]esi.om OCCUI' spo:ntaneol.lS~.y Inanimals tha,[ 3ire stressed 01." giv'eni. ruJt:l:l.colytic a_;geFl!ts, when.lood is resmclt:ed aT when l3!I1li.m!]a]s 3ire rest:rminoo in cages,ev'elJl ~holLl!g!h ,these para:lli1l.et"ers have not been. ]!ll!vestiiga'ted sj's~eElla'l1ica.]EY' .. Mm'E.'Ov,eJc, none of the.se cirCILl!mstamJes applied, since. 'wma~oes contain no muooly~,cagentt:.s~ rood W1ll!S p[ioviided ad libUu~nand t!hem:~s were I1i.o'~[iest["a:ined., It was d;:o s~g:esl!e.d!~hat:. because the lesions were possilbly of ilihm't dlLl!["a:ti.on, they were :inciile.nlat not velated i~D ,the te-sl rulallteria~ and wOlLl!M have heeled spoFUlaneolLl!sly, Un:faI'tl.lna~dy:. none ,of the-se a:s6ump~i.ons was mMnille.d byliu.rthe.[· expe:lirnen.tatioFl!as no samples ether than those at Itthe' end of the 2&-day ,e:xpel."mu~n't\\v,ere lakeill'!! to probe mto the IIEim:llIDgalFld J:e!i'ersibiHty of the mcid.ence o.f the stmn.ad1i.~e.s.ioIl!s. e]ear~.y, the results o.f these ilihree studies sh.olLl!]dhave pro]]!lpted more eX!perilTIll.elJl~fion ~o iinv,es.tiga!te. in more detafl tihe e.flfe..::tt: of GM.tomat'oes 0111. SllEo.rnadi his'l:ologyand, wl~t is eVeFI!. moreimpm:'ita:rnt;, these studies shouldhave been extendedte Inchade lite possible ,eHeds o,f GMtomatoe8 on boththe sma]] and Jar@"~ :in~eslilnes.

Tne"ed. '01: dark red pirl!-point lesions presentin~he. stoenaeh ()i~ female. :rats wihi.dh were described as necrosis wowd besenned 'erosi,Qn' m. ham an paJho.]ogy, w.hidl may have seql!JJe]ae, such as Hk-eFldange:lirn.g

351

Im.emoITha,ge.Erasrom cannot be ~emlted 'lITllUd', asunr-recliklalb]e haiemm·:lJhage can oa:ur in I!te elderly human, pa[tkulai'+y on low dosag:easpirlnro rrevelJf~tlu:omboIEil: events, and sY:llergy wiJtr,h.t[ca.II.SJ_geiJiktomaWes milYOCCllli:l:. The <liS'Sumrtion trn~th.e leslons illIire re.1a~ed to stress does noll: eXiP~am ·the low iIDl:ddenceinot!fter groups, pa[tkullldyi.n. the second study. The relevauceand sign.iifkance oJ gaslir~k eroslons Infhe human may be a matter o~ life aoo. dea:th En the oMe:r.a:ge :gil'OIUPS' :H has been imp~ied I~,ha:~ pat~10~ogis~s in generllJ] nll~ght [lot repod su.c:h a lesion but, ift ,the plieSelJl:~ eI'illI of vex.a:!'ilous l:i6ga.t:h:m~ men'!'ilOllWOUld! have been made lin any humaft palh.ologis't's J:lepOl:t~o avoi:d an. aocusarion oj I!'leg]i.gence. 'fi:hi~ lITIl.ay nolft he T">equi.l'ed m vetelIDar}, pat'ho.logy but these rat stud~e.s WeJ1e done w:iil:.h huma:iJIS m. mind and therefore the palh.alogy Bndmgs mus'~be put mth.iis human CDnt:ext ]ilr is prooaHy l[rue to :su.gg:estthat ,these ]esions are oJ shart dUTIlJItiiOFl, but the serious nature o!f el:'o&ive~.esiJOoI'l!s sh.ou]d Flot ~ m.11.daH2ied. Thls:is the lITlllQIle sea:lOUS IooCllJu~e seven out of 40 rats e,a,1ti1!'lg' GM.~omatoes died W]il!hi.n. 2. weeks.. Ihe F1a:itm:e ()'~ ~ihes.e deaths was not speci:ned snd I~he e'videlJice :ttha:t '~hey were nOI~ re.1atecli. to the ingestion (ilf 'h':ms.g~llik '~oma~.oes was inconcluslve.

ln a fuIitther deve]opmenJt, the 'Sdent]£k Comm~n:ee onFood o·.hhelEu1'OpealFl Cemmis:skmDi:r.ectO[ca:re 'L (200Cl)oo:r1icuil.'red wiitih t:he iCDnclusi.oll[lea.dhed.in '~heUS Food and!. Drug Ad.miluirst[ca:tiou (l994!.) melITllaralFlaum. In thei!:' opm~O.D, a·hh.ough 'the results showed. aIJlUFLe'Xp]aiIDl:ed djjsparHy~~h€"ywe[le not S1lprOo])[ive of a sum tance-rela too. effec:~of 'the FlAVR SAVRTIM tomato, HDweve~', lit lis ]]kely '~hat ,theEU Co.mF.lilliJUee' ]i!]ay not have seen aU the p:drnary data and thei!JJ." oplinion would ,therefore have been based. OoninmF!lllp1e<re evidence. It irsa]s.oregretl:aH,e that, by <JJSITibirng tihega:stric ,el'Osl.O.DS ]]'1 rats ID 'an :lJ!rt'efa.at of g<1!va@e' studies' ,the EU COF!l][miil1lreehas :in fact bbe]]ed. the sde:ntlistsCllJITy:ing Old ,the work as m.c,(}FlJllpeteFut. .As these- eros.~OIliS WN">e found at the end of a 28-day stlmdy dur:ing:whkh. 1,60 ratswere gl3!1i.'a@!i.ed twiice daiilly ·w]llihtama~m."S, ];It ]suntIili,e]y tha,II ,even. poo:l~y 'h"a]FLedJ.v,o["k.e:rs wou]d notheve become more

compe~elJl:t, so as '~O avoid cll!us;iing such <lin anolITll.a]y.

Effects. (lin body weigh:~ Food intake

alla arga~ weights'

ItteOO:lJldu~oFl of ltili-te ENVm:ON pane] !!hat ~eediTlg[l1ts an GM to]i!l.ail;oes {C:R3-623} krr 2Sooys had no eUect en w,eigb'~ garJlJI, ~eed lntaliean.dorgan we'iglli'lts l:oll.l!M noi~ be .~ustHied becausejhe starliiogwci;ghilils Qllthe rats 'We~ie so w'icl!dy d.Hle:r.ent - <li :r.arnge of 1310-2'58 g (± 33%) krr ]i!laFes and 114-1'75 g (± 2.1 %) kw .feJnales -that finding sirgnifk'arnt dliHe[ienoesl:n wdglli'ut g1]ID, feed. lin~ah <lind OoI'g;l3Jn wei!glli'utswas not ]iikdy. lindee4 'Weight g;lJ!I.nS va[':iied between wide liim.l!1:s CU12:-230 :g ~DT males and! 46--l~7 g lm' females) lin. 2.8 days.. Evenm:u:l!e:r.~hese liJoFldHions,a]li!hou,gih 'fEhe avea:age S:lillII!tting:weigh:t ofthe male rals g;lJ!vag:edw'ilffi-l CR3--623 GM toma~eswas 'fEhe highes't (148.1 g)" theil' &;a~J.ve~:ght (316,5 g}W<liS ~Jrte lowesLAocorom,glly, th.e rats g;l3Jvagro with. GM ilroma~oes gJ'eJ.v th.e Fea:s~ O'J the four gI'oups ,o'.f m,tts. 'fihe feed IrIJl.'ta.ke o,J ~ihe di!He.l:'enl gr0i[[p.s llJilso varied between · .. vide l]]l!~.i:~;ll3J--2[1.3 g(o[" Filla]es and 102-153 gfm·females. Not smrr:iis:ing]y~the ~eed COEliveFsi,(liJi. dnciency (wei:ght ga.mj~o~~ ~eedlnffike) of female rats an GM itoma'~oes (OJ52) 'Was sJigftl]Cm1I.t~y (Po:: 0.05) ]ess tI:!im:Ji il1.hat (0.167) obtained. !for fema.1e~ca:ts 'OF! COlJit[lo] nalJl:-GM eRS'iom;atoes.

Ille 1a:rge[-ange ef sta.ding wei:gh!: dHJerenoes also exduaedthe possiNHty of I]nd!ilJlg si:gn'i6l:anl differences inthe o:r.g;lJ!n wcights of 'lI:ref,om>gmups o.fra:~s. The standard dev:ial.i:om OlE mean va]llreswe[lE!' vel)' ]aJ:lge, lin someinstances mQ11e' 'than .2.0% .. It Is ,It.he' mOore rerrI!a.rkable iIfIa:t, eVeFI under these liJollidiitri.ons, rome di.flfe:rences :in Ol'galFl weig.hts w,ere ~oun(t includiing I~he'~es~es fOor males <lind Ilthethy:oo:id/ pa.rarlr.iJyro:i.d! fo[' females.['~.ndm:g no :signHlcanrt differences :i1Fl hiodhelITlllil:al, haemaro~ogy and. ophtihaFrnology parameters behve.el!'l GM:ma IJI.o.n-GM~omaOOes was lJI.oi~ unexpected ,eiitihel''., becauee ()If·the ]aFge miJtEia~. body .. veight dUferences.

Overal], it is re~ttalble ,!that these·m,f taxico~.oguca~. feedmg: studies were poorly

152.

aes:ignecl, ;as ;a gre,a~ deal oJ ,enO[~1t..'Ovork and moneym.lLlist have been spent on '~hem. and !SO lITtlll.l.C'.h.restOO. ont'lrte outcome .. T:hefDNs conclusion -that F.LAV!R SA V!RN presented IIIO mOore darrugers tD C(}FlS1llIlIJercs tha!FI OI."diilJlal), t,oFl~atoes does not '~here.Fore a;ppea.r ~o res~ on gpodJ science mJld evldenee-wldch mlLliM stand up to criil:ical eJ(am]fIllJ!rttiDFI. Ra'~her te~.ling~y! th.e resll]ls oJ rhese shLrd:ie.s have nev,el· been pubHs.hed irrn. pee[~rev;]ew,ed jOl:!:ma[s.. The !>irudyas desrn.bed. noil: only raises questions about Ibhe d.es.ign, me~hods a."ndcoIlI.dns±ons fDr Ilthis sma}, blLlit: also whether '~heYCOllld have any gene:raill. va];idi:ty fDr oi~her GM. foods. lin rhis ]n:gh'~, lit lis the lITtllCllie sllrprisingthat: a:ftel~ these stlLlidies lithe .FDA liaS OOCJ]nired no IlIulEriil1.oFla]j IDxico~iClgi£'al resiling ,0fol1ter GM foods.

Al!'ell~nsts ChaMiollil1 tlJL IbelMicilIl~alresist<llllllt GM, mI1l1.ize

Due tD 'lthe UK g,oveTIJI.me;rut' saUe]!lllpt ~o place ,Chal;dDFI LL seed on. '~he Nabo:nal LISJI1, a pal'!: of the snprortilFlg evidence submitted by Avenlis cOFitained clarita on the COFlllpasiJt:io[1l ,oJ t!;v,o lines of seed. 1;0 .estatbHshthe:ir suhstandal eqlWiJ\lalence tD ,the coruvent:ioFllJ!] pa.rent El!l,aEze line, T1l:e·e'!.d.dieFtcea]so Included the :reslLliTIts of a. 14-day rai~(ee.diiJIJI;g Sll'udy. Am this is tD be tol!l!l1l:d lIifI a f1~e depos.iit.ed by the Il.tinisltry of Agricnlw.re.. H&heri.esom:d F.lood. (MAW) WlJt:&! the Ih:i!os.hUbldUY (B:r:it~sh UhI'ary~i.le~ 1·~P17).

CompQ5i~'Onillilnil/y5{5

En t:he absence of specifying !the or~;glll ,andlcond:it:iom o,IculIrl'i.v:at:ioFl ·of ,tthe dHf,eiL~ent 'Q\..:I alJtdlJlon-GM sl3!mrIes, strict sdeutific compa.risolJls conldlJtorit be made be'f:ween th.em. However; even lLlind.e[·lh.ese condifions, th.e lJo]!lllpo.sHTIolJt ·of 1'1L4 and!. 1'25 'GM. maise ,expr-essing ph.o.sprunofurlcin acety]t:ra1JlSfera&e enzyme {lP'Al'-FRrnrEm) s.howed many staHs~ca]]y s.ignllicant ·diJlferelJtCf.'si.n fat mlld ca:r.bohydra.te COFl.teruts in C'olTIlllpari&on m,th [!lOn-GM graJl:n s.amp]es, and .fl3!i~j proiltei.n and :Hhrebe!:'!iveen s.Hag>e sa:mtllpJes :b.'O]!lll 'GM. and nDFl-GM. lTIllaEze.. Thus, .~1:1te conclusion that GM ma1z,e i!s noilt 'lTIllait:eriamy diJIferern.f

from 'CUITeiJtl 'co[ll]l!lIJel'da] variettles cannot be regardeclas v:a1id ..

.Repeated dme ors! to'xicity ( 14-ddy (eedj'~g) study tlfl (ats

Therationale fOl~ this stl!JJdy\ovas to assess t!he C1!J!mu]ativ,e toxidty OlE rAT -lP'ROTIEIN given w[cais lJn their diil?t ro.r 14 days and. to provide arational basis fur '~(JMkologiica] ri&k assessment In man. Al,1tholLligh test:iint;g of lhe PAT - PR!OlEKNcalFl be mmFl1lelJlded., thls stmiyw<lJs no substlmtefer the nutrifional ~estft:IJIg of the entire GM. p]ant, seeds, vegeta~v,e· partsand :si.ll3!ge ilFla]] targe't l3!lJIiFll,a] speci.es.Vliri!thout these, the potenit:ially harmfnl,l].[1lilFltce;noodl l3!IJI,d lLliI1Iprndicmb~e' ,effects OJ 'tthe'gerte UalJiSfer, ather mmpoFleFUts of~he veoltar and ge;ne insertion (posi!ionm;g effect} ClJilIDlJit be established or exdncl,ed.

Unfurmnatdy,as the desiJgn olh'!he experiment was lalLli]ty, it 1:S diffiJCiI1h ~o dmw va]rd CDFldlLliS~.onS '&OlTIll. a Jeed!Jmi,g stljjdy. carried aut wiJth .fi!ve rats pergJl:oup,iI1l w~mth.e s'~ltjjlJl:g weight of IlL he ruts V<:iorioo. by more t!Fuan ±W% {53--8:2 g for males and :n-'l4 fuT Jem<lJ~es) rntiher than ~eusua.] ±2.%.fo:rany differenees to reach. si:g[1lHkanlJe, ~!Ftey needed toexeeed ±2.0%, andte achleve this liFi 11 14-day study WOlLli]d have requi.red calaJ8t[iophk e:xperi.m11enlaJ] ·oo:ndiJtiolJls. ThefiJve rats per gil'OUp were nOT housed 8.jint;g~y end lttereJoil'!t their ]lFtdi'!{~,dual feedinrtl3!k..es eould not be morui~ored. even thOlLlig~ the huge differences in ~he s;~ltjjlJl:g weights 80011M. have' Jed iro lITt~ajor diJf:ere:lJlc.es ]!F1 the :~eedin,'I:l3!k.es ofth.e :~n.d!:ii\'idll.l.id rats .. Mal!eove[", th.e group .feed ]ru~a.kes'OVere nat mewl1m.'ed.CQTlil:bniI.l.QUs~.y. There were fOUl: gI'onps oJ rails (five ma~.eneITJ:1La]e[<1'is peii g'l)onpJ m the experlmeiJIt. Howeve[",I:<lIIt:s ]!F1 gI'onp 1 were fed. a dliHeil'eFUt die~ (Mll;at &IOW) from '~he a~h.e:r three groups and il:he:reFm'lf gFDlLliiP 1 was notarpmrriJa:IteFo[' (stall']stical) c(}lTIlllpad&ons. Itte dieit of the second gI'onpconlltained 5 g l;;ri and the fuhx:l~'OlLliP had.:IO g 19-IPAT-PROTEIN mi:xoo liFi wWh 45 and n g k:g-1,respediveDy:. oJcomE!t1le[,dBill. (SOIAM:IN, .KUBA Muh]en A:G)~.ow :soyibean pmtdn diet (11% [caw P['ot:ern). The diet of th.e Fourth gmlllp CClIJI'tl3!m.oo. 50 g kg-1SOJAMIN bu·~ IllolP'A1r-PR!01'EW. Thl!J!S, f:Of ~tarltist]ca] mJla~.y1>.ls, the second lJJnd.~h.iro gI10nps OlLlight t'D

353

have beencompared W]ith rats in t:fle tolLl!['i" g['oup,. Curiow;:~.y, .a]t[hQugh the ma:ilFlt;llll:gel organ ,of the PA I-PROTEIN foot'o[ea'!:!;; was thedi.gesti.v,e bead (:md pancreas], the wdghts of dll.esew,el:ena~ measueed, ltui.s is a maJmc eXper:l:mlll,elJlta.] desi~ fuu.1i~.

The stad:iirn.g wdgl:d and the Ieed ]nJl'ali.e oJ the lh.OO.twOlLl!P lhlghlPAl'-F'lROTlE]N') were the hiighest, hu~ they ended ur with the low,est Hnal hodywcight Th.is m.diica~d an elevated me;tabQillkacti!v]~, p[lobaHy irlll.du,iJed. by the PAT-J?ROTElN,. Om ana~y&iis I[),f '!Ta!["]i1noe {Al\JOiVA) shows ~atth.ewcight g3Jm fair" bolh.ma~.e and. {emaile I:l3!tson the rugbiPATPR!OTE1N d.iiei~ (g:raup 3: 65.2amd.42Ui g fair" ma.1es and ~lLa]es,[lespedivdy) was sign.iif:i()l3JrI!t~y (Po:: OJJl5) ]ess i~han~ha'~ I[),J either the Joudih gFOUp (ooilioitrol 72,S and 48.:8 g .£0[' males and fe[l1Lilles,[lesptL'ct~v.e]y) Dr grcoup 2 {~aw If.IAl'-PROTlEW diet: 73.4 and 44Alg . £m~rna~.es a:1li.dfema~es,. resrec'Di'!Tely). As PATPHOTEJN reduced .. teed!. CO]1!V€':rSIOlIJi. eH:idef.1i.CY, iJtt :is poteFlt]a]~y harl!1li1l.ful The OtIDc[uslonihat "tt'Fterewel'e no diHeJ:IeiIJi.ces wmch. coul!d. be attribu:red. to 't['ea:tmenitt with. :lr.herest a.Tti.de' was t:hen~fa~5e :m),t Vl3J]~d., S:i.F:l~.ila,~y, that: "the:rce we:r-.e [1.0 ch;llilJl:ges on ,.. clin]ca] biochemistry and. urine alJla~y&]s aft,elc 14 days' ]S ]lOft valid either as the authors' O\llffi. results descri][,ed di:ffle·F.e11ces be1tween ,the .tw0lLl!r!> in gllLl!ms.e, dho~esle.[lotIT~g~yce.lid.e and! phosphoHpiid lev,e]s,ind~()l3Jt:ingan mcre.8J§edmetabolk liunctlmlilli] load ]rI! :~he ["a:ts.];t~ ]s unexplained wibuy these diHe.I1elJl.ces w'ere dismissed. by the authees as mcideFl!taland u.m-eb~ed~o the UellilEmefl1l. OurAr\!lOV A l3!FI!a]ysi.s l'e""elli~ed that ~f! lll!rm.e output in Fats em the h.iighiP ATPROTEIN dief~ was signiif:ka,ndy (PO:: O.Q5) reduced, md.icatmg tl'eatment;-r-e.~artred e:ffeol:s (urine 'OlLl!t:put of 5.4 3JlIld 4.4 m] .(OF males and leF!IJ~es m. grouf' 3 1;'S,. 7.1 and 6,5 ~.bc males allid.{ema)feS,[\esped:ive~:y, lin c.oFllil·o] .g:IDufl4).

The large dHlerenlJes i.nthe st8J~.;1EiJfI1g wcighrtr of thetats prolbah]y prev,elJl~ed. findilFl@j: sigrnfi()l3JFlt differences Inorgan wrights, HDwev,el';. everl under these ,oon.djjt±om~ rn1t:s led the h:igh Ievellf.lAl'-PH!.Umw diett (th.ifild g[loup) had.tbe l.owestUve:r, :iliY]]l1msand sp1eeillwdgh:ts of all gl'Oups (eventholLl!gh the d!jjHe[lenceswHb ,oOlIT!J1oiLswel:e not si.gnHlcanit). This is ef ra:r.ti,Cll]]a:r ]]]I~poTlance. becense the ]]IlLacrosoopic find.iFlgs iriJLd.ka~ed

d.}':UIllUS fod. in 2(I.-4Q% oJ Ifrte aruma.]s fed diets iJOIlJita.iimng~h.e PAT-PROTEIN.

In eencluslon, the deil,ign and e-XeclLl!tlOfl I[)f~th.is f:eed.iFl@j" study were poor lliFld,oolJlh:a:ry to 'the authm:s" conclusions, fh.e resu]ts illlidi.ca~ed. trea:ltment,-:re.1atoo. eHects induced by PAT-PROTEIN (l[)Ii u.nspecified origin), lite reslLl!]ts 'tlFtereJm'e ,oau.1.d. DOt be taken asevidence t.hat~he t:r.a:iJlster I[)f~ Rs gene into ]]I~aEzel:epresentoo no r~sk w:r~b.e rat mlld, by i!Il!£e:re.nlJe:,. far hlLl!malJls, pa.:diC1!J!~,a:rly as IliO gu!" MstalDgy studies ha.'!Te been. comF]e'~.ed so fur. Fina.1]y, l3! reeent publica,tion (Ch.iJler el ,(ii.t 2000) showed! thaI: ONA survh ... ed!. lin :iirn:tad:&arm oir"s.l.iJgili'utly fmgm.entoo lrnile!SS ,the GM maize'l<v,as :bellil: processed ex~eiMli\'e]y. ll1e["e-fC!1'e:,.the po!>S~,biHty 'e%I.s!ts tha~ wi.th. l!l!IJI.de~oce.ssed maize P~''Oii:l!lI1cl:s h.tmll,aml!s arnd. animafs m.]ght- be exposed. to the UN.A used. in. the gene.ti.c engineering .

O).I~(!I:>i~ioua.l S~u:dies rliblislhe~1 in [Peer~lie'v~ewif;dl ~olUlnillalls

!3e-Hm.ng its limpDrtance.in botbt haman 3JFld animar~. nutrlficn, a gt1ea:t deal of .aiil:entioFl! has been given to the. mmpositional aiFlllJi]Ysis OIff hedJ;!ci.de-resi.S1t.a!Iltt and ot!l'te:r GM soyiJoealFls, Several pubUcalii'(nltSarfleal'ed.in fIIutri:tkma~. and a~he:rjouma]g de:m!l.ons1m"3ti.ng the comr0SJliHoFlJlJi] 'slibsit;8!JJt:l]a] equivalence" of GM lliillld. nOl[]l~Gl'!.1 soya. Thus, i:t'l<vas claimed that the ]]I~aJCiJ50l1!Utri.elJlt campoil,il~on of glyphosatetolenml sDylbean r(Gl'S) seeds l'esul!ongliroFll thebcallls{oDllIamon .of CO]1!'VentiOlIli.8J~. soybearn ¥I'11.~ a g.elJl.e enoodmg 5-eno.lry:ru\'yiLsbt:ikillilffite- 3-ph.oophate syntl:msefrom A;gmmcterium,. to make ,th.e soya hetb:idde resistant, W3JS equiv3J]erul '~O that oJ ('onvenlEioFl!<lI.] soylrealFls, ItI:i:s app]i.ed.equally to' GIS UlFI8flrnyed. with glyprmsate fPad;getJI:e el ,r1l" 1996) or sprlliyed. li'I<i1h th~s hel:b:icid.e (Tar ]ore'l i'lL, 1999).])t W3JS claimed tlhailt the results oJ prm::imal,:e dFtel1lltcal analyses ef the cofll~eruts of crude FW~d:IJI, 0]].. a:M!,nb:re. car:bob.ydr.llJt.es :md 3J:mtll.mo acids o~ selvent-extracted and roas~ed .oF 1ll1Jtoastted saybearn meals of 1ll1Jsrrn.yed. GTS and control saybe-ll!lJl. had shown t'Jh:a~ illI][ these ]i.nes were

154

slll!!J.sta.nhaUy eqlll!lvalent {lPadgette e~ ,al" 1996), 5:imiilarnilll!dingJ5were described lor ~I:ayed GTS (Taylor et 111/" 1999). Ahh.crugh. &1S aFFea!red!.~o be true .fOil" ]1!~o~~ma,C1'Onutrients, several si!gIDl!~.I].eim:t djjHel.\enaes be:ltween. 'GM and cO:i:1I:t[\O~ ]JiIJ!.eS, such as in ilsh, fat a!Ili:dClliibohyclLm.t:e OtJ:Il,tenms, were also fuWJi.d {lPildgette e,t «1.,1996). Howeveil", these wel'e' noilt l\ega[,Ged 13iS hl3ivmghJio.]ogical sJigwJ!ffi.e<m.Cf!' ,

A e~oseil" :i.nspeoltiDn oJ the data En I~e pa!pers, however, revealed lilrua~ the sialis1Eica] o:ml!parismll of ,!!he ITIIllilITOFl!l:I:tri:el1lh of GM and nOIJl.~GM.lmes w.as noilt !5-cieFl!t:iiHcaJilly valid. ]mte.ad. olH OOlllIpariilll!g: tihelil"amo[IIJI.t:s m a slll!fAdeF!t]y ]ar~e F1!nmberof sa.mp~es of each. ~.ndhd:dl.i.lJJ] G[,S w:lJtth :its IJJrpl'Opci.aJlEe ind!iv'id- 1.i.lJJ] pa!rerui line grown sJide by side a~ I~e same location and ha.Ev,eSJ~ed a:t the same 'lime to ,eslabHsh.1icvhether they we[\e 'substiliFl!liJilUy 'eqlll!:u\;<alenJf, wiha,1]: 'tIJle a!n~ihm's CO]1!llpaiil'OO was a. large mrmber O'~ dHk·:rent sampksb\oE!lll dif~ ferenJ~ locations aeid harvest il!:i!1llles.. As growth ,oo,lldJJti:ons have l3i. II111aaOrrnil.lll!.ence on seed compo!SiiltioFl(, ~ihe mng'e of the amounts o.f CDFI!sDruenms m t'ihe diiUea:eFI!t samp~eS;,l:eg:IJJ:rd]ess of wffil:et!her ,they were 'GM. or :lJiOn-GM., was !SCI g[\ea:~ q:!!::10% or more] Iltha:~ Iblrte ch;l3!!Flaes of Bndmg sta:t5s11:ica]]y siigni.A.C'ar1i,t d.iiffe[\eil1ces we[1e unreal. H ]S po!SSiJb~e ~hat .&om a pradica] point of1i.d:ew lithe vanatioI1l. :lilll! P[iOtmCOI1iCeFI!l'lr"ation. oJ Sa!mp]es of theth.:ree Ilnes o:fbehv,eell 36Band 45%wonld faUin't:o the·norliu] mnge of ag;ronomic vl3ir-i!alhi.Hty o:f ooybea!IJI.S and tl:!ie[\e,f,o:r.e mm,ay not be 011 major eencemfer ag;ranOElil'Is'tB" How,ever, 'EMs cnmparisaiJi iSlJl.ot sltriot enough to esibab]i!s!h whether the geneltic modi!f:icaJIti.on iilll!trodiuced. l3iFlly 1!]iFI!init:ended comrosiJEioFl!alcha.nges. ,.vI:ml~~s[\eE!l1iarbb]e 5sthat~eve:n w:lltthth.ils app:raach. Et1i;lliIJi:Y sigruncant dU!lJi:ges ]n macrQ:a:mtrieFIt~,eve.lswe[ie ful!l!l1ild. Thus, ~he c.]a:lF!l11 ·of 'suJbstantialequi!\'alence' of GIS liineswith. lJI.on-GM ooybea:lJlis not suppartedby rigcmons scient:iifjjc ,evidence,

The potentjjalim(porta!r1iC'e m. ~umaJl hea1Jt::h o,jnarural isofila!vo:ntes, snctu as geIl!istein, dai:d.zeiFI!. and eoumesteel p1'esen'~ in soybeans, is~nem.uy IDmgniized. [tWI3iS, '~heI1etfo.Te.. of oo:nside:rable mte:res~ wh.el~her a!IJI.ychanges OOCJl]]])?'d lin these' eompenents 13iS a resu]t of genetk mooiifiicati£n Here Ithe publiished ,evi!d!em:e 'is oentreversial, Thus. wh:il1eill

some smdles no :mel3irung:fu] diifiel:'eill'tces 'Were I-epm~edJ (lPlJJdgeUe g~ ,aI" 1.996; Tay'~m el «1., 1:999'), l3IfI! iindepeooent st~d.y da.llI1Led that GM soya samples had eomJsiefl!t'ly co:nitai.ned!. sigm.fiClliFl!t~.y fewe.[" ]!5-oJilarvo:nes lLhilfl! the pa:[\efllt OLlill.tii.vaI's {La.pre et 111/" 1999),[[11. 'Oile resiPect:.a]~. 1JJiU.&orsl3igr.eed, i.e, t.ha:~ ttheisoAavone ~Oll!teflit oJ soy1bea.n. seeds showed eonsldeesble varlIJJbii~1tybel1w'een. sites end was dependent OF!! IJJg;ronomkco:ndliti!om. Hewever, Ll1rpe et ,al, (]999) weFl!tful'l!.her a!Ilid dal.I!I1ied ~hailr, wM~.e the variab~.Hty of the GM samp~.es was m.d.eed rnnsiJd!e:rI3ib]e, cenventiona] soybea!IJI.S slrtO'l<v·ed less variation ]FIJlso!i1a:\mne eontent. As the isoAay,one ~mder1fl of soybel3ins mi!glht IJJH~d human health, tlhel.'e needs [0 be Et1i.Ol.'e a'l<vlJJl'eness of pol':eFIJtil,a] health. prob]e!TIIllS due~o tMs vMiiabmty.\lVlhi.le 'lttepI'ec1se details oJ the ,changes in ]s-ofil,a.vo:ne 'OO1lJIte.nJt on geneiltiJc modiACllitiJofl! w:i]] h;lli\'eio be e'Sta:h~:ished. iF! '~heliitm\et ,to ,eFlSUI:e di:ruca.] cOFlSi!~tency, the o:rigin a!IJI.d Ilte actual phyto-oest::ro~n~evels iF! !5-oybea:1JI. may need il':o be smndardi2ied.

In t'he study bYPl3idgene et aL (1996), no signifiClliFl!t da'fe:re:m:es we[\e .fourtd in the levels of aIJlDFlJntl'i:efl!is, suc[has Itrypsirrn inihi.bi'io['s. lecitID and o]i!g'OS8Jccl:!ia,cnde ffia,Mence fadoI:'s~ Io.ehv,een so~veFl!hf.·xJ[raded, '~oastoo. or untoasred 'GM 3!nd nm:Ji-'GM soyhel3in seeds, However, the .oomril.rlsO[JiS were mede by ,the SIUI1ie melt hod as fu·r ]l~llcl.'o:nutri.e:r1itsail1!d ther-efure il:he~;l3!:rge Eantge of na~ura.] va.riability exdnded the rossibiHty of A.n.d!iing sJignri.I]Ca![1i't ruHe;r-'Nlces,.[n~eresl:itIJi;g~Y, in. :si:ngle so~ailll! meal samples ofeac.h (iiI the b;.vo GfSaiFl!d pa.l'efl!t !Innes, thetlY(psm m.h:n.bi.tor (a]oo a majio:r 13iHe:rg/eFl in soybe..aFl) COl1!teFlltW.l1S substan:EiaHy Mgh.e[",. by almost 3O%.,in one of I[hetllovo GIS l~iJiJes.lIov:i:th 3J smaller :Un.crease m. the ol[h.er. No 'IT.}'PsJiiFI iilJi.hib~:~o[' a!Ilia]yses wejie pedm:E!lllea on. '~he fmJ'tein isolste 01[' rr'Olltein rnnae[1[t[;aite samples origiiFI:1iltiiFl!g: hum the meel samples, Allthoug1ri!there were ather CDIIIllpos:iholJl,a] &Heifences En the~ processed soybean products, ]i!1 Is djjUiOLli]t 'to decidefI,om sm:g~.e d.eiea;Ffilina:ticms 1Whelh.e[~ these WeI1il::' s]gni.filcanltly different: .01." not.

In concluslen, there is IDsnHicieut e'Vi.de:l:JioCe ,~o date to decide .... ffilethel~ tilrte composHi.on of GM IJJnd conve'nt:i.oFl!a] soybealJl.$ is eq[luiva1eFlt Oir no:[+,. In .fad, SOITIl1i.e data, partic:ulal1y ·t!hos-e for phyoo.-oest:oogelJlS, 'were

35.5

sigJli.ifi:ean:tly cll.He.1)e(]tt Purthermore, becanse DO't stl.~d~.y co]1l~.parnMe at:mlIposJiitiOFl!a] aa,m were used, ,the. cilse(Olr 'eqlLl!ii:vale:n.ce 'Wl3lS FLed properly estaM.ished.. There iis 'H!FtereJoliean a!bvrou!lo need for .lim1:hennorecdt~cal srud!±es.

Brief re.leI'Nlces ,~o GMpo'mtoes, pa[tkula[~y those expressi.ng .Haci1tus .t1!J:otrifilgieru:;;is (l31!) '~oKi~ C'm:1i he fouFLd m. non-peer-reviewed book chart-em or other a.rtildes.b1i. mos~ ms:ba!Flc-es, lihe&e cOFlta.ID no dam and are ,therefore olr mU]e sc~eiJI:ti.l]iCli.'a~.ue .. There are 'two eXiCep'lIio:ns, one of w.hkbt is .:llliaEt~de on the safe'ty assessment OIJGM po't'aJoesexp[iessing It:he soybean g~ydftin .g:e~l:e' {H:ash]];J!lo~o et III., 1999a}. HDweve[", it is F10t qui~e' deale w!ha:t the ausheeswanteel to achieve becsuse, l3lt ,th.eexp[iessh:ml.~evel of glyemin in potatoes of between 1:2: and 31 mg g-] tuM] soFlib1e pro~eJ[Ji,no s,iign.fi'ClJJFlt iimpwll,ernenns iiill'll lh.E' pro~ei[]l. COI1tent or ammo add p[iolfHe CO'lLl!]d have-been exrected.ktdeed, rtthe' reslLl!TI.ts iill'll the pape[' demoFl!s1traJted Illihill the ~ota~. pmtcin coill'llleFl!t oflLhe GM potatoes appeared to be sign.ifl:ean1tly Iessthan 1thilt of tilil:e' control line and ,that no ]]jIJnpro'l/,e~lJtt in the esserut~a] amineaeid prnfHe wa!lo achle •• ed eiitr:her .. There appeared itO' be subslant]a] differences in so:mtn.e Il~:la:mt~i~ 'b<~~weerli GMand. controllmes, and the amolllilJl.'ls of bath solanine and dl!i}mFl!~.ne increased in Itthe GM Iines, U ]s, ~b.er.efore, n.()I~ quii~e deal" why il"vlJJS cla.1E11'ec1 !tty ~!he aushers lm~theilr GM Jines were equivalent to the parent ]me Il!f1i.d colLliild beutllised as &llifely .. The ,othe. more recent study is a mFl!v,entiJ..onaloomro&iil:ional ana~ysills oJ some macro- l3lill'lld mkro[JilLl!ul.enits of tlLl!bers fuiO:IT.I~nsect~ and vi:rus-res~:ll1'.a!J]t potat.:o p]an,ts {Ragaill'll ct al" :3000) pel~.fm:meJ by methods wlhrk.h C1liTen1tly are accepted by mast nave] food reg)!]laltory bodies.. A]Ir;h:ough these sl1iDwed. some si;gnmca.n:t differences ID I3l numbee ·ofrubelr i:Onsl:ilw.e:nJl:.:s, ]f! theillbsence o.flax.i.co]ogrcil.]Jrnull:r:Hional ,animal stu.d.ies iit is cliHkuh to IJJIKerla]FI! whel~herth.ese d.i:f:ferences could have l3lFl!y Malogi.C'al e.ffe.d~ on :hllulTIl3lm/ l3lm.ma.1s, pd[ikul<l!;ri].:y I3lS '~hese aJilivent.iioFl!lli] analyses CDlLl!]d not na.v,e

revealed. l!!he' deve]op:mtnelJt~ Qil a.n.yllllJlknowfl possible io:x:ic! autiiElllitriitil.ve componefl!ts .. A.d!dmo:[1I.3J]~y, known lm.'ti.nlLl!triertls, such I3lS ].ectms O~." ,eFl!:Zymtilie~nmb~~o"s, were not lrrndlLrded. lirn the analys:is.

GM '"rce ]ines eXp[iessiinig lithe !;Joybean g:]ydnm gene lrave been devdoped {MoElll.ma ct et; 1999} by a ]1IlIIethod :!l~.mii~aF. to tihaitt lLl!il-oo.f.or GM r0ta~Qes. The gilj'd:n.iin ,eii(p]'le&Sion~e •• elwas b.emeen 40 and 50 Ffng glyciiEll~n g-l iI'.atal riee pmiltci.n. The GM.I.'rce1.'Vl3lS dailliliilec1 to cO[Ji:lalJ[1 20% more prortte~.n, but Hsmrnslu['.e ,aO:[Ji:te[Jit was Fess.tbum. tih.llJ11 ofthe pare.nJt line. Hawev,e[', :~om the papeT,i:t is FLat qnite clear wh.ethe~." the innieased! poo~ei![1I.oo:nJtent\\vl3ls dlLre It'D the decreased moilSlru.re GtJJlil:enl~ oJ the seeds because 'itW3:S not Slredried whether Ithe values WeNe exP])esse-.di fur air-dried mcf;uUy dried seeds, Thns, :mtn.ostor the argu'meIl~ 'in 'I:.he dils.c1l]ssro:n of wl:!iiether Ithe ~l!~gh.er. pro~em. ]e1!reR was due ~o the' pas:itiom.nge,f{ect of gene :iirruserl:i.o.n or ]1I~eta~boH.c interferenae wiim . have I~.o awaiJ~ d:lllIifiClJJH.oFl! 'by fud:Fte[" work.

Several Hues of GM. coil:lon pi.arlJtts.have been developed using the gene eJl.codmg an meclrdd.al proteIn fI50m B. .tfu,fli:mgiensis Sllibsp. k.J~.rs~Qki. These .had. ir[Jicrearsed proteeiliDn aga.iill'llst t[he rniljor ]eridop~ei[-an iill'llsed pests af.ooUoFl!. As coU:omeed. is .alFl~.mrmta:lJtt source of ail fer human iCDFI!SlW:mpti.o.n, and ml!l:onseed. and processed oottenseed meal :for animal f:eed, e.x~emii\'.e l3lIllllJ]y1timl wDrk ~'I!aS been OOIJt.e to' e8Jmh]jji'lh'!,i'! .. -l:If~therthe GM ]~:nes were 'substanliiaUy eqlW~valenf: tn eonv!m'ttimml lines (ne:rbel~ich et al., 19%). The Ieveils oJ protetl'1\,fut, 'ClJJIDo.h.ydmte, ]1Il..olSU]re, ash, aminoacids arnd fatty acids ]FI! the inseetpwfededUneslieven!' da.iRliled to beaompara:b]elicV:iJtth.~hO\Se' fouoo 1.0. wE1!lI.mercial varieties, Mioooover, I~he levels of ar[JinnlLl!tElieFl!ts such as gossypol, c.ydorropenol.d fatty a.ci.d!s end al:lail:.ax.iin w·ere si.m~.1arjJc~o or less thalli I!tose m. ~O:[]I.Il,entil,o[Jillil seeds, Thus, the ,GM varieties

355

A. P,tJ\5zl.;;ii et a L

we.NO: s~ge8~ed to be equ.iva~en:t to COFl!\'eFI!tiOIltlJl) seeds and just as F1!llltil'iltlOill8. Howeveir, the ~t<JJIllstiC's used by the <liufno['s wel.'e :icl!eilll!til.,ClliIl wth.ose used! with g]Yrhosa:~E"-resJjsta~l!t wyaand thereforecould be si.mli~:<u]y criticised, Ahh.ough. tire content of known CDn!llllil:u.e.n,ts fe]] mbetween ,the wkl!e I'aiJige ef values of commercial conll,entiO:llllJl ]]ines, ~i:s did IlID'l mean ~.ha:t t:h.ey wel~e ,oomposiltl.ona]]y ,eqm]\'alenJt,. parlkmal'ly as envlronmensal !lJ1:re.SS cOlLl!TI.d l'uave Iill;a[jo:r. .ailll!d lLl!npredicmMe ,eHeds on anilElnU'h'il,ei1l:taIld lD~:i.n ]eveb {Novak and Ha:sllbe:rge;rt 2000). Ihus, w:iltholLl!t: a:rui.male%pel'imenlalilo:rn._. r_hiis approach could [!to't reveal wheth.!?ir lJJFI!y new il:Fl!d uill1klTK!'Ii'!rn. tm;:~ns/ame['geFl!s had been. created. or IllOI.

GM 1iI111.iZ!e

A glyphosate-'~O~eI'anlt {Ro1uIll.dh!J!p Ready} maize ]i:rne GA21 ha:srN'ent]ybee.rn d!evelfaped. Ell: wasclaimed (Sid!ihlll el' (it, 2GOO) tha:~, e%mp't for a .lew mi.llor diflferences, wmc!h Ib'he a1!J!jl:hOl:s~ruru:a.l1e un]:i_keDy [0 be of hi.o]og:ical siJgwIil.I]ClJiI1i.ce, 'tl:iieres1!J!]ts of compos..i!lEIoIlJa] <iilll!a]yses of PWJ;:]l!ID1tl3Jte, Ho['e, ammo acid, faili'~y aeidand mineral contents ,of the g['arn, and prm;:.lFJJllllte, fibre and F!i][inera~. co.nrt:en:ts ef fDra~i=oolleo~ed. from 16 Held Sc'ites lOver twO' ga'DW~[]jg seasons Sch.o-wed!. ,that cont[\o] and! 'GM ]:iirnes were c(}]'_mplll[.gb~e. The- COlITlJilplJIris.o.n ~s carried out by a method!. siF!ilila[· ,~o ,thlllt des.aiOOd for GIS soya (Plldgel1:eel ,mot, 1996) and this may theref,ore Rot be scientilfica]]y ['il:gom1!J!senough(m'~hees:tab]i&hmiimili' ef S1!J!ooll1nt]al eq1!J!ivalenlJe.

N lI!~r~tionailfIO!~~coll(JIgJio(al S~u:dliies [PlLll~ll~shed ~liII [Peeir-lrev;ew~dI JOlUirlil<lliis

As pa.I'l of a safety assessment (),f GTS, the feed.ing1i.'alue, wholesomeness {HarnNllo.nd et ,as" 19%) and posSclbletox:idty (HanJiso.n et at., 11:996) of h-vo majP[" GM lines of GIS .. ve[le' compared V!..-[th. those olff lithe prufNlt line. Processed 'GTS ]]Ilea] was 1ndml!ed. ]nit!he' diets O'f[cats, broil!er chickens, ,ca;tfiisn and

dai.ry cows at dJie 8IJ!]illlLe concenrttmrt]oFl!s as 1n cenmrercial non-GM. wylbean mtions.. Rats and d;a[il), cows were fed. '~hese diets :for 4, broilers for 6 and ca:tfis..h.~or 10 we,elks. I~ was clal]]lred thaitin. rats, ca:tfiisn and broHe:rs the gmwtih. and feed. COFl!veF.si.on eHiciency, :in 'cat[Jsh the fii!lletaomposition, iF! broHe:rs the b[\ea:silt muscle a:rnd. {ailt p:ad weliglhits, and :in d;a[hj' ,aows m.Uk PI:OdllICtiO[]i. and.aomros~.tlon,l:Umen f:emlernmtl.on end di;g.e~ti.M.1],1iies were Shll![~llI:rf,Oi' ootih Gl['g and!. p'lJ!D'entalllnes. Acroromg~o the alll'[hm:s, fihes.e resw.t:s mFlifiliE:med ibhartt tine GTS and. parenit-aJ~ines had slimHar feedmg va]l])es.

A a:111:'i.ca.1 e-va]lLl!a:tiDn O'f ,the rat smdy was hampeJ:edJ by fihe lack of adequate prima:ry 1lftdivl.d.uaR data 1illl! :tthe p:3!per". Th1!J!s, rtthemwas no full descriplilorn of !he rat diet It appeEJ]E ,that the tota] pw~einoorn.teni'tt oJ ,the- diets was adjuseed 1\0 2-4i7g l1;;_g-J diet tD be ]ro.nitroge.nous,"vi:~h. P'U'HiJiB Labo.:ra1tmy Rail' Ohow by the addHkm. ef 24,8 g O'f GIS and pal'e[][~ :soybi!?EJIlJ mea~S:.J,e8pecl:i'lle[y (-to%. pro:te~n), ,to a base die-t AUoornparisoiJis WIe[ie' made witjeum!1rs fed rnF!ilmercial P\!J!iEm3 'Chaw .. The' protein rnncellttra,m.onin these die,!;s\\Vas, hawever, app:reeiaMy higher than the USl1lJi] ~10-16% cTud!e protein and. exeeeded the pro'le~n req1!J!JJreETlli!elJlts ofthe rat, This extra pro'~~n potenl:iJaUy could have masked any p06&i!b]e 'tmlliig.ene pmdl!Jd effecilts, pal1rcu- 1ar[y with. the raw lLlJ[]Jp:oo;cess.ed so-yiitlean d!ie:ts 1n which. the GM meals w·ere 1lftcOlpom'led o:n~yat th.e~e\'e] oJ 50 or 100 g kg~J O'f lithe d.iet. Thus, these meals ,oiJilytep]<tc.ed 8.5 aoo. 17%, reSJPfftively, ofthe toltrlll] pro:le~n ef 247 g l1;;_g-J diiet,. In otherwords, the 'GM soybelJlIl! protein 1lfttln.ese meals was dHl!JJtro. by oth.eii dli.etary pro'lei.ns iby 12- and 6-fold,. resredjjn~ly, produdng aI'lotlJie'r possi.M,iE' ]1Illll8.kfing efred. The composition of I~he centrel Purlna Chow diiet 'iiFI~he ground raw s.Qybean feeding gludy was []jO~ described, This lis important because the idern:tHy of !the raw control soybeans l!Fl!cl1!J!d!ro. m !the Purina Chow COFl!tIIO] dliet WBiS not specified.

Inlttefeeding ~tudy, fom: gro1!J!rs: of rets :(~en males and jen .(eF!ilillJ]eS~Jl each gt'oup) singly housed. w·erefed dictsQ(Jrnl1l!iiIJi:ing the

357

pa['eFllal liine 01' the GTS lines (4!0-3-2. 0[" 61-67-1) :&o:r.2.8 days. No individual values {Ol:' the:iF.,:anges} for feed :i!rutah or hody we:ii.gl}ut were giiven. Thehllll; di!agrnElltS o'flh.eoo.mh~ned body wcight of rn.ts .aj~ tihe end. of each week of th.e 4-week expe[imeFIJt were I'lJJthel:'urunlm..-:m;l]Jtiive .. Howevel:',Hwas obsel':!l'ed by ~he ;l]Ju~hars itthat the Pwilrl!a. Chow~'.~ed male rats ~w sigrrif:iCIJJrut~ybeUeI' than the th:reeex.per~.mental gI10ups fed toas'te,d soybeans (i:nd;u,dim'!!; 'lthe pllIrNl!talline)" Tbdswas atb."iibl!J!ted ,~o retit:er comm.ercia~. pruocess.mg. However, t[he bar a:i;IJJg:n'l3!ms abo im:l!±Cait.ed rtha:t theg.row,tth :in 1the gl«Rl.plfed'l\ri:~h one ,of ,the G[,S Illnes (61-67-1) Ji.vas probably equ;l]J]~o dm:t ,of t[he Pmriil1l3 Chaw-(ed OCinoolan~th.el'etfore, by im'llfere:m::e, 'l1.hese ratsalse glee.... s.igruHClJJFI!t~y retit:er [han. the otherltwoe%pe[imenta~ Illnes (the GTS llne <D-3-:2 and. the F;3!I:NI!tal Iine) , This a;ga,]n UilllJa,erJ.i[rned, the irmpormnoe I(If gi.vi.ng i:ooi!v:icl!.mll dafBi in pape['s, witihout wllil!kh.a~s d:i.fficuh '~oassess 'tI:ne resl!J!]ts, Sjj]illllHar'~]i't the!fe were no iirndivid!.l!J!al data(m' mganweIgl:n:ts, such as ]~ve:r, Ud.neys and '~es:tes... However, i:~ W3JS cleimed t~'I!:l:t the kidney wciglrnts .oJ them .... ' GirS line-fed (and parental conJltrol?} male rlJJts were sigruHClJJrut~y h.iigilitel:' th:lu those of thecontrols, wihi~.e t:he tes:tes of the pare.ntal line-fed FlJJtswel'e- signll]ca:ntly en],a:rged"Acco:rdingto~l:ne autl:nol'S~as these' dHlenmces Wel1e' neither dose related nor on]}' shown by the pal<erulal ]m.e., they were nOiIt caused by geFlf!:Iti~ modiflcancn, Rather cmTol!J!£ly, thewd:gl:nts of the stemaehand :inleslilnes, the main larg:et arg.m iim. illiny nuh'i.t~.o:nalles~ng. were not [<emrooo. Observetlons were nolrecorned. on o~he[~ organs-and no hi.smlogy appea:rs '~O have been done DFI these tissues cil~he:r,.l'.I:n.e m';l.y tissue whid! was subjectedte ]ill~krosoopy'l\v.as tine pancl'eas, but the des~rirpl:il.O:[]l of the fUndings was qua'~:iit;l]Jtive. On]y ndnlmal jo rnli~,d Ieslena were fo:u.nd I3!IJId these 'we['e claimed ito be CONllmOFl '~O ell gml!J!!ps. However, under i~h.ese co¥l!dHians, th]s WIJJS nolt smprisirrn:g because no FI3!IJI,creBim~ hwerb'lophy was Wl!J!J:nd, Thiswas pliobaM.y due ito~he eJIfeo~ of the l!J!nrusua,]]y h,igh. dietary Fro~d:[1l eeneentration, w'hi6'h.,as the authors pointed! Ol!J!~ masked. andJoil" di~utea the b:iologkal e.f:fec~ of tihe trypsin inMb]wrs" This Is of parti.cr]]a.raorn.cem. beceuse ,~he' trypsin :inhtib]itoroo:nvem.t ,of GTS Hnes in lLlifl!poocessed

soybel3!lJlwllJs &]gF1!~HClJJFUt[y higher than In tbte mrn:~[\o] Illne {Pacl!gette e~ ,al" 1996},

It is Feqett;l]Jb]e thilt the des.ign oftWs impormnt Eatfee&i.ng stl!J!d!y had such.l!J!nliorrnFlare omissiens. Itis of partrcilllarl:'aolllCeTIl. lOhat no h:istDFogywlJJsarrarelltllYCIJJrnoo. ou~ on guittt~ssue,. Thus, IROlJeccitkaill. ''I\vmik is needed I~o decide whelEhertl:n.e leoomg value of GM and non-'GM soybe;l]J!E1Jl is equal 01:' nolL

Chicken sway

The broHer ch~.clbm.feed:[rng s'rud!y's experili"i1l€'[]im] deSJign doseayf:o]~owed that otcemFiI~e[\d;l]J~ [p.irlliCittl.ce and tl:nm!e.fam it!Fte resl!J!]ts shouM on]}' be in&icBitJ11i.'e o,ff :Iilile' co:mm.ercia~ :~eedingam1d productien va.]llle of the va,riOll]S ooybel3!lJl ]itrnes. As the d;l]Jta were pooled .6l'DNll allbirds fed on the' same diet, ii~ is not e3JSY ,tto see what, Uanyilh~,ng,.was tihe sigwull.I].e:m,C'f." oj the small di.Uel1elJlces fOlLlind in the Slru.dy, such as riFte sl~ghfly rower bodyw,eigi:nts,. breast IJJnd bt Fad weigihts ob~ai.ned w:i:tththe 'GTS lines (p0.['t.i:cula[~yw:i'tth. Gffi 40-3-2) for Ittheilllilliz:l:,[jOFl o,E GM soy1beaillll. It WDlIU have been better ito measure the ruut[ililo:rm]rer(OI.~]llUI!f1tce of i!J:n.di.v:ial!J!al h:iims (01" SF!ll;l]JU groups) fed. on d!iHe!l'eFl!t diets and ~lli1en mNllp0.[iE t~'tem. after statistica] analysiS" In the absence of d:rls,. we ha.ve~o [<dy en the authors' cenclusicn iIh:lt :th.e des~:grn. of the 'e%pel':irnenit gllJve theupper llim:iJl of: differences in w~:gh~ gai.n of: 3.5% snd g;3!i.n/ feea[';l)no of 2% and that tihe GrS lines vs, pBi:renta~~~.new,el:e],,'VHhm. 'l!!Fuis li]ll~jt. Thus, wHilt this l'eshiction, I~:he k'ediing vahie o'ff~h.e GrS~mesf:or Moilers was practically equal tD '~hat of the parental soybean ]me,

Catfish are .e:xcd]eiF1!~ and hi.gMy seFl!siltive i[nd.ica'~m"S lol:' the .feeding VIJJ~.lI.e ef d!±e,1ts~ u was ebvlous hom. the results :that, simi.l;l]J[: to' :~he f:irnd,inv with rnts, one of the GI'S liines, 61.-6'7-1. was superior tothe ather lines '~GrS 40-3- 2: and 1t!Fte paremal ]~:ne) in mostrespects, l1fius,nsh on. G'FS line 61-6'7-1IJJte mO!l'e, had betterwdgl:nt gllJin and g;3!i:rnJ feed rat:io and w1eiighed more at the .end of the In-week stilldy than tiheotihel~s, even ,tthough thecomposiiltiDn oJ the .fiiUets fa!OEll:ll these fish WIJJS not &ign]ficimt~.y di.fferernl. Thls signl,l]ca:nt

353

A. P:usz{ai et al.

d.i.ffere:n~e in pe:rJm·lTIl1l.l3Jnoe must, thel\e'~O:ret ~nd!kare !;!hail: ge_ncl;]c modllicaition may not be as :['ep:[;()dlLrdble as im has been claimed aFl!d. liiha,t t<he feedi:rng value and IDIl.etabo·HiC effeds ,oJ GM and paren~ Hnes llJTe lJI.o!!a]ways 'subs:~.arI!tla]~y equiva]eFlit',

~~.k poodurn.oFlaml!dcornpos,ilioFi aFl!d. Fei~ tommlFlce data in the ]adatiing cow study sJ10w,ed some sign.Hlican.t: d!:lifrel.\eFlcesbet!ioVeeFl oowsted. diets cOFl!taiI1!in.g :t!he d.i.f~nit ]iir1ies of soybean, illi1d.kallng a lack oJ'sl!.]bslalli1t]al eql!.]]valencer "bli vie·.v 0'1 t¥tes..e dliffur-eni.ces, e'l:'en th.ou;ghw,e may no'tt a:t presentl"now all thei.r IOOD]Ogical/ rI!ll:tl:'lt:i:onia~ cons.eguelJices, lit may be diffkulJ~ ,to lTIum:tam the view ,that :the feediFlg va]ne O'f IlJte GTS and parenl~ linesis equal. and. fu])tther wod1;. is needed. l,oestablils.h whether ltthe 'Gl'S Imes are sale-or n.ot lm, h.mil1l.l3JFlSlaniimab.

fu:iI".ens~v,e' studies have been ,earned! ou.'t ~o ascertain the safety 0'1 t:he' gelJte P:['Od.llld, 5-elllolp:ymvy~sMkimai~e-3-phDSphat,e syn;thase 'KF4lEPSlP'S), wb.lch IeIJlOOS the soylbea.ns glyphoS,lJJte resi.MlJit (H3iITIoon et ,(;Il,t '1996). UIJIJm1::m:JllJJt:ely, :!there aile- sOJiTJJlleHa!ioV's ln these !?Xreri]IITIH~IJt:~S, the JiTJJlost i!mportllJfI!t of .vh.i:ch. isthat IDt the acute gavage' studies the i)l!.]lltto['s did!. not use the ,efiL)1lilliJe iisolalo:ed!. from GTS lines but instead th.alfr.om fschErj,d~~ mlL A]tihangh. tihey were at pams~o ~lOwthat the ElP'5PS enzylTIllle SllJFlnples f:J,om.~he two som:ces were sim.Ji]a:r m. ]ad olf g]ycooy~aittion, m.o]!Bi:l!.]]ar siee, reaction with. a poolycIOoni}] .antfi.-EPSPS llJilllItilbody and elJiZyme 8SSllJys, these rnethods do not h.ll!ve su.fHde.nit pOW,eI" ~o Slli'tO!iOV unequlvocally w!hetihe[' theywel.\e identical The Il!ufuors '~h.enl!selves poij[IJ~ed mod tmlli rost'-'lTansJ!at~D."!1al rnod~f±ea6Oon of th.e cornp·~e~ed po·~.ypept;id.e chains emerging fro'IDIll 1'lItte rilooSOJiTJJlesmay be done- dH.len~nt]y ln two suclh e""o]l!.]tim]ari~.y distinct Hie fO!l11llt:S as higher p~.afl!t:; and pmb[11otic bader:iilll. Am.iidiati.o.n, .a.cety~illIil:i.oFl m:nd p[ioteolytic pr.O""" cess~ng Ci}U have such majo.~:e'Hects on the oOIll.f:ll[·:JiTJJillliildion o,I the protein. as to' make lheseg/EFleprodlLlds behave diJiUeJ."eFl!t]y millie

diigesltiive sY!5lrem. Thus, the use of the E. roii recornhiil!lllmt pro~ei:n fDF the acute mice gavage smdies lTIl1l.l3JY m.'Ilalli.dLailtetlTi.e Il!ulhars' C'()ncll!.]s~,Qn 'that" '~e gene p['odl!ld ]Tom soybea!FI did not hllJveanyklxk eff:ecil::s. 'f1hese srud.ies lTIlliLIS'tt be re-dcme Wiith.th.e gene producr isobitOO .IirOI!lll the tra:r1lsgeNc planit be'.fOre !he resl!.]]ts CDllkl. be aooepred. In any case, in such. gavage s'l:1!J!dires, yDilllJgt ra;r!i.dL~yg:row]ng llJIJI.1Jrrn.a]s must be l!.]sed. 'Ito show any di.sfuld effuat on. gl'Owth, As llJ]~ an'ill1lla[ weighs were unchanged in. the exrerimeiJi~, 'lthe iltesit system used. ('DuM nD'~ have d.e~eded alFllyeffect wi~essthe conOOC)]~uern::es of the gavag'ing had been diiSllJstl'O'U1.s..~eedmg stl!.]d!nE!s with the gelJie prodl!.]ct :~:IJt yOlHl!:\jI"ap:ld!]y g::ww'ing rodenss should be fhe pI'e:fe:r:rcedl: method rOl: the demonstration o'~ the de]ete[~ous e.flfe,al::s.

nle o,ther f:bw m.th.e experi.meFital des'igIDl! was 'th.er:e]i!ance' on an m. u.itm sirmm]a'red. ga:;t['k/inteslina~ dligestilolll.asSllJy,wh.id:n was llJlso ('a["I~i:ed! OU'~ with the .IE. roli recombmant gene pwdud. To dbta.in physi.olog~.cany va]id. :resl!.]]ls, i!twou.l.d. have been ne~e§sary 'to l!.]§e the gene' prod!md iiSD~ated. foo.]1I] GM. soylbeaml! :liFI! an ji'l uiwasSllJY :I!F1 'the rat 'COle other slllJ'ita'Me a!llI.lma]s; §e'eRl!.]Mo,e,~,(,ll" 1994.)oniiu.IUeooirng ITlal Th.Ufl,~t has been shown before~hat the kidney be.aFl (P~.rasroil1s vllt:gtlil'is) O'i-illilTIlly~ase :llFl!bUib:it:or is f;ljj~.r~y s:rnJb]e~o p[1oteo.lytk degradatien lim .the' rat gJi],t (Fillsztai e:r: at, [995, 1995Ji), but, wheFi i'l::s gene was 'eili:pI'eSlSed~n peas (P.is1,im satfm!tii),H VI'as ra;piJdRy d!lige.s.tecl and ]lrmdh'atoo. m. the rat swmachl sma]]initestiine ill vioo {Pusztai! e.~ ,ai" 11.999). This may have contributed. to the saJetyof GM. peas far mts and, by llil'lll1ere:rllJe;. possi!b]y fOr oth.er monogastric mammels, Thus, in vitro dlges- 1:1D."!1 llJSISl1ys may hevelittle relevance r!:o the saJety 'Of GM .~d cropK

In 11 s..ep:1llI~a'~e leed:irng study ,(Jreshiima e.t at, LOOO},the possiMe haemful effects oJ teasted g].yp:h,Qsa~e-re&iislaFlt GM soylbe<m were in\'est.iJga:~ed.artt :300gkg-l irlll.dus,]oifl Ievel :l1FI the dijet" oJ ra~s and mice, After feed!iirn.g these aniima~s fOor 15 weeks, FlO sJigou~.l]am~ dii:f(en~TIces in nutrir!:iofl!a.] perfo!i]]l]anoe., orgaml! d.eve]opm.e:nil\,h.is~opath.o]ogy of the thyml!.]s, ]jjver, spleen, mes.e:nte:lic lymph. aedes, lP'eyer's patches llJfld small iilJltest1ne:. and. tlll.e prod.ucth:m ,0f[gE llJIJI.d[gG humceal anltiibodiies between GM end nOIJl.~GMH.ue diets were

359

fouoo.Hiawe'v,er, as rats gt'e'l\v less lidrualFl 3(1 g:<md mice no:t aJt al] in 15weeb, the CDIl!d[HcnJls were sOIJ.IJtPh:ysiologkal thai!! no va]!id cnnclueions cou[d be dmwn. ,b:O]iJil these expen]l!l:eub.

ln ,:1, majiOT commeI'd,a~sCaJ]e bJ,oi.1e:r dJt'idk.eF1 (eediin:g sh!J!(iy w:irl:h. rations ClJ:lll'la]nmg·t!:ansgeiJI1c Eveni~ 1.7&-deri.ve.d lit m8!lZe :iTl!vO'hrlng lZ8C1 bErds (Bmkeand Vlachos, 1998), it w,as da1.EIllIec1 that FlO s~aJttisHCaJF[y si;g:rlliHc:1:nt d1!~ (erenoes m Sl!J!F'!.dVI3J] 'Oil" him. wdiglhls helw'eeFI birds ,fed. d:iel:s ,oorntammg GM ml3Jize, Eveflit l76, or mil. :isogeFl!~!c palief1l:t maize ~i:ntewere (oulJld. Indeed, briMs fed GM E1IBL];ze mtiioos a!ppeared. to lmve ~ign.if:i:cimJfJy belite:r~eed. CDFU",'ersro[1l [catiosaIDlJd an i.mpil'OvM. yreM o.f hreastmusde,. However, the authoI"s caiLdkmoo.:1g;l3J:irrnst the Cl)ndusion th.l3Jltt t[h~s enhanced pe[h:rm:1noecauld he a,1;IT~,but,ed. ~o~h.e Hi maize per st!. ,It i!l possible that the resl!J!]ts 1TI11light have beeFI dl!J!e~o slight diflfe:r.ences :in theove:rI3J]1 CltID1!POSJi'liioFl of ltiheaiets, This ]S l'easoFlaJh]e cOFlsidering ~ihe~ern;gth o:f tms srndyail1Jd posslb~e problems. of CDl1!sJJS'~el'1i:t rue'l1 preparailrionom a mEl~mercial scale, Minor d:iHe"enoos iirlI. cOlTIllpositioru such as the s]ightly~owe[" prolltein COIli'~ei1it o,.~the 'bM maize and fat COFl!~el1!ts ,of ,the dil.,ets ]l~.l3JWUiJ],ed. to tllile scaill:e of tftllis :mal.mabe :~he resules more relevant Ito ,oom]l!~:erda.] 'tIJillln to academic sci.e:IJI;1ri:ll1C studies,

[napOldrry feedingsrudy, itwas d:1.1.lITiili,ed that-the GA21 ROl!J!ndup' Rel3Jdy maize-based diets gave simibr perlm:mIDJiJCe daea ilF1 g'[\l)wth. feed. eff::id.e:ncy atodrar. pad wcigh:hs to d~ets ClJ:rn:mming the pl3J['ental CltJll:rrol line 1(51.&1111 ettd" 2000), HOW'l''V,el:-.ihiJs and aJ si:mtlli.1a[, srudy carried. out m Geml.l3Jfliyw'iitr:h a ma.iz,e HneexpI'essiil'1l:glPAT -.PROfE[N (F1ach.owsky mild Aulldch, 20m.)1 w,ere coIltlmercial p[\oduc'tficm. expeaciime:n,fu;: andmadelittle c-.onmooiltion ,to sc:ientilfic safe~y assessment,

ln a separate s~lJ:dy, maize Wl3JS genetically modified by the tralJlsfer oftheg:ene of egg 1.vbt.iil:e <'3!v:i:diln lID ]TIl,am the seoo. resl.st1l!f1tt~o :storage insect pesli:s (KiEamer t!l aJ'" 2000). It was also claimed rhai,t tJruis GM Etlll3!:llze WI),S safe

for mice as a:ppa[ieFl!tay:. wheiJl.., instead af a balanced diet, theyweil'efed soldy on!h.]s mop, the mi,oe sl!J!ffJen.~:J! ne liU eHect:s. However, the n1l1cf." used in the experiment we'readl!J!llts wh.ich dil.d not grow at aU,aifld l!tereJO[ie the cOIJI.dl!J!sio'Il!. ~mt the GM maiae was safe ]s,at best, pt'eml3Jtu['e.

D±e:hs cOIl!ta.in.ng l:itcans~ern,c peas le!l;;p[lessl:l'1lg :thelraIlSJgielliefor irlJlSecHddaI beatlJl. a-l3Jmylase mMbHor (-3 gkg-l peas) atrnso different mdl!J!sioIl! levds l!iI1Jth.e d]cij 30001' 650 gkg-l, w'ere subj.eded. ltD :ruutrlliolJlal. e'!Ta~lJ.llJldion willi rats In aJ. UI-day feeding Mail (PlLl!szibail et al., 1999),. the Fluhiti.cmaR pedormanllJe o.f rats fed GM pea rue'l:s1.vaJs cO]iJilp.l3Jrro.'I\vHh tho~e obmmed w:i~ raihs pari[~~ed iso-pmltei.n:k and il~o-eFle[~getic dreittsmlli'mmmg p:1renlt-lme peas I)lFI!d allsoladalbumin diets spiked wilt'h 'isolated he.an and. pea m-amylase i.nh~hijlto:r!l;, respecbvely, AilE 300 gkg'-\ but no'~ ai~ 600 g kg-lindusimli Ievel, i'1rte :lJI.u!:ritnonal. va]ue o:f die:~oO:lJitamlng umTlSgenic or pa:renitt peas was not sigJii.i:Hcanitly d:ilHe[iel'lt.iEven.a:t 650 ~. kg-l, 'tile diflferen.ce was s]Tf].l3J]I, F!iliaitnly because t~le ItraJFI1!lgenica:]ly exrres~ed pea :recombi:lJillllJi:t a-amy lase i:m-ui:b~~ol~was quickly (m <: 10 F!iIin) d.egrr--ad.ed in the mt: diigest:ive 11racl' and '~~efor.e iitsa.ntmum:ti.v.e e.flfoo~wl3Js abolished, In cOFl!t[;ast, srlHlJlg the paren:tal ]l:nte pea diet with the stable bean a-amylase hl.iJbHor reduced its ll.l!J!trifioIl!::d",'a1ue (PlLl!S:Z'~llll et 1]1" 1995, 1999)1,

In dltiis s:tlJ:dy, UFItorhma:tedy, no gut histologywas. done oil"lympl.1ocyte responsiveness measl!J![ied, and ith.ereJm:e ,olJlehaJdi ,to rely 01'1 the eva]ua,liion. of: flil!J!rlriJttio'llal p:1mmeteJ:s ,ttha:t are in~lereFIt]y less sem:itiive iirlI. orner itD find possible diJfEe['eFtces in me,tabo]k :respm:ruses between GM. and oenventlons] food comp:!lJI.ents, A]~lrtl)l]];ghtheI\ewe[ie si;gnifrcaIDlJt diUeren.ces lin the de",'eloplTIIlen:t of some OFgll!FI1!l~ 1TIl1i:1.mly the eaecuna aJiFld panc['ms,. F!ilDsi~ o:rgan'l\'Vei:ghts weloe re'Dl!arkaibly slmflar. AJ~ '~h.eeFl'd. of '~he srudy,crulJ.tiolus Dp~m~s]JJl was expFe:!lSootthat 'GM. peas could be' used ]n the drein;; oj farm l3[n1.1TII1,a.]s, pIlTt~!C1lJJ]arly:1!t the' lo:wllTIlmdLen,:~e' le'll,e·]sil'ecommended iIl!

]00

oom]1Jille['cI;lll practike aeid :if the pW_gI'eSill ·oflLhe ilH.mals :wasmoiEl!l:~onil. aa.l'efullily. However., this relatiively !l,ho]j~ feed.ing srudym,t:h mocl!est o!bj:ectUv,es ·ca:rnlol~ait~h.is stage be tafu.en as proof of the sa:~ety O'f GMpeas WI' human ,crn:lsu.mplikml. There iis a: need. ·t·o ·carry OJ!J!t fIwdhe~c a!l1IJd. more specifiic risk assessmenatest~ng procedures, which. must be desl~ed and de",'e1oped wHen human censumersIn ]1]lli.nd. ]k also has to' hekepit En ]1]][indth.llJtonly one pB!G'Eicu~mc liirn.e ofGM peas wastested lin whkh. the en;dogNlous ilJiFUti.nl!J!lt!:ienl· le'llds1.cve['e !Seled:OO.~o be simii~.llJ:r to dJlose of 'ilJle p>ll!rNlit pe.as" lin some oltter GM.lli:rnes, h01.cve""el',I.edl.n ~.evds col!J!M vary, up o:r down, by lJJ factor. of fol!J!G'.Mol:'eove[", ]!F1 some :f1e.ld pea: culnvars, such. as l.al!J!m_ lh.e con.()eIJI:~[;a.t:iDn of t:rypSl.n i.nMbiror m.=a:sed hy ilJibou~ 2.4% and illie Chym:lotryFsin hy 'IOCl%.,wh.iiIle :lthe haemag~lutinatmg activity decrea:S'ed by a fad:arof tol!J!lc i!FI '[he GM Ineoomp:JI1Jed with its parelllt (AP1l]szJta:i., unrubllil'hedl This slil'N1~l'hem the argun]eiJit th.llJi!'. illlJ the saf,ei~ assessmentof 'GM crops, many lsnes should he included and lh.llJt~ .&'omthe results of a smgle GMline;. no blanl!eil: appl'oval sh(}l!J!M be given ito ° tihel, lines deve]oped, even if in i~ne' 't:ra!l1lJSooTIll!a:tioll the seme vector was used and. cal'il~·ed out lJJt the SlJJme tjjme.

Thereheve been four iiFld.epelJld.en.~ studies on diffe:renit GM tp0taJoes.

The Sl3!lfety of transgeruc pOlf.llJooes I?xpre.ssing the soybearn g'~ydmlJt gene was evaluated IDt ilJi short (4-week) rat feeding: study (Ha:sh.i:mtliJolO' et at., 199%}. With an iin~erestmgEl(pedmefr tal design, contifo] :ra:ts and the experimental g:u.~Dl!J!pS were fed the S:JI.]1[lle cDntrol cemmeeelal diet. HaWe'll!eF~ :!:he rats were ilJibo .dal!]y furee-ted by gavage w]lih :2 g .0frespecWwe polarD lines kg-I bodY'Il'lldgh:t The potatoes used. were a pm::ental control ]we and two trnnsfoI']1]1tedlines, one with tifie gliydnm gene and another one mth a desiigned glycmil.n ~eiFle {oodiFl!g .l1o:ri10l!J!1: a:d!dHlcmJlal. ]1]lletrnon]rn.es

:iifl the geille p.['odiud), respectively .. However, there were a: number ,01 poobl.ems with tlns smd}'. Thl!J!sta],rhol!J!g~ Thodafer.e:lJl.ce :in gI'owth.,i1eed iirntake., blood cell count, blood C'J)]1]lpasith:m aoo. inl:er.IJI.llJI. o:rgaFl! weights betw·eeFIt'ihe groups was w]!J!IJI.d,tlheuIllc:e:r-lllJiirnty' as ~o wilhe,t!he:r the animals WHe fed with raw Oil" ho]~.ed/ba.ked polllJ1EoesleaY!es a queSltion mark ove[, ·the~:nte[pI'etatiO'iJi. ·of the resu]ts.

An~:iJi'tte['esting, mam:lyWs~o~.ogyt study was caT.~.ed oul: oiJi.the Ileum of ll!11l1ceted wiifJi1 POIi!'.llJtoes iltra!!rISfo:rmoo w]tih a .B.. thulI'i:l1!giC'l'/S'is va:!:'. kurstll'ki Cry]~ox.in gene. As a CC!!Dlt:ro.1, th.e effed Q1f i~he to!ICin itseH wasa]so ]FU'Ilestiga'led (Fares mli,d.IEl-'5.llJyoo., 1998). U was s'hO'llYTI. :that bath. the delta-endosexin and, 'loa. lesser eXilre[1i!t_ the Bt ro't'atO'ca:used vmus ep]theal;a;~ cell! hypeljttrop'fIIy and muhinude.a,DDn, diJsrupted micmvimcal!J!sed lIilii.HochDndri;a;~ degelJi.elCa:tinn, mcre.llJsed nmllii'bers o.f~ys.osomes and autophagic vacuoles, and :incre.ased!. m::iltivatlo:n of cryp'tiPalJieth ce~ls. As a resuln, itwas :recommended. :I!ha:t 'it!hO~:Dl!J!gh ·tests of ilthese new' ·types Oil gelJietilca:lill:ye~ineered ,C1)0'p!l ]1]lUSi~ be made '1:0 avoid the risks befure ]1]lla:rketirng'. UFlifu]jmna:~el}', some flaws ilFl theexpe,imeFItal desiign detract tro]i!TI. the st:rengJ~h of the ccneluslons, The ]!iliJOsit iimpoT-'lllJfI!i of ilt.hese was ·that~ apart :&omi.n.d~ca:[jjng that t!l'te· gene used ii.rn. the t:iI:ansJonlll.llJDon was the Ct:"y[ gene ham B. .~h:r.iriw!tiefl:sis var, b!rs~akf, lihel"E.' W.l1S no description of the B~ POlffillJtoeS. 11:Jte geiJi.e I?xrressionl.ell.e] In the GM pola,lto was not g1'1l.en and it was D.oif deal:' \'lI'hetihel' the potatoesin the d±e.fwel.'e· cooked or Fa.V .. MOl.'eove!L, '~he amount o.f ttthe Bt'tax.ll1lJ used. .tor sU!rp~eme.nDFI!g the pola,toes 1Wil.lh.m the CDntrolpoiffillJro did was Doit specitied either, This m;adeH bupossiihle to ]!i],aR a qUll!f][~tati'!le m]i!lpacisoF! Oil the ef~1Is on the iileum Oi~ the Bit pota~o wHh those of the spiked cDnlrol potate diets. the assl!J!mpltion !:hat t::he i!~,e.um is themost important ahsorpti.ve pBl:n1t of~h.e rodent S]!i].llJ]~ intestine CDl!J!]d also beargued aga.~l1ist. bec.mse90% Oifa]] nlulirreill!.t ilJibisO'[Wtio:n ]F! !.llJdo()CW'sin the jfejiumlm . .A.s tl'ui:sWilJiS mlI. ellflOtI'o:iJi. nn.icrosOO'f'Y smd}" the :llJi:a~ion of th.e :liIleal samples was

361

nor!: done 01] weMl,-orient·ed, ~ectiW1S but on. dhoppe:d l!l!p :Hne tissuepieceaand lim,po:rmnt' dela:i] oJ!vm,us ,or:ga:lJtltzallEioFIJ 'was lihe[,e'J!Ol)e Ioet, Firl1la]11ft the d.elrbaren.diolltax.irn~indhlced hwerp]astrccha:nges an ]]eal,..ilU sh.ou]d have been d!em,o:mslTatedi by Nl~easul:fi:l1Ig ceU pmlHer.aJltion alFlld m]toilElc[--afue~ ]n HeaJi, {and jeejunal) cry[pls ICath.er tlhan on fuevH.i. Ho:wever, d.e~P]te ;these &ho])~.com~ngs, .t!hills study has esta,H.ished once a.nd fmc allthat, ]]1 COTh'h;ast' ,t·o geneml belliet exposw:e olf the mouse gu~ (1]e1!J!NllJ i~D l!ihe Cryl gel1le prodl!Jd has caused, pra(m:md hypeI'tliOp:h.ic and hyperp]as'ldic chll!f1l:ges in ce]]~ of ilthe gu~ a:lo!IDrpHlie epi1!:hdi1l1m an.di.C3Jn lead. to mucosa] sensifizahan (Vazquez Padron et a'l., 1999, 2!OOOh). "(hils sho'Ws uF the: f;lJJ]hu::y of &rawmg CONllJol.l'tting coFldusionsb50I!lil ii'l vitro 8.1.mulated, guit proiteolysJis tests, C1eady~ ClDncems ;lJJbout: the possl,b~e Iol.olagkal consequences o:f eJi:pos'Ul'e ,to GM faod shol!l!M be ad.d:ressed l!l!ndel" til viva conditi,ol1ls OOC8JllJJSe, even if 13!f1i, f. coli pmd,lITct breaks down ill VltlrIl, th.is doesnot necessamily mean. thaI: t[he same ~erte product eJ(PTeSSOO in the 'h;al'llSJge[1i.k cmp should slso bresk down,

GNA. GM potiitoeS

Some O'f the ])eslm]ts of 'rn:t(eecHng studies w]1iu GM pO'm[QeSeMp[lesslng the s.nowdmp (GI1l1:i1\\i\hU5 ~dmlis} Inmilb ]ectfu (GNA) ge¥le were slmib:r t'O ,~h.e resu~b of Fares and lEi-Sayed (1998). A. part OlE '~hisl'''''Q;[l;. GOThce:rnirng [he ,e,~f,ect of GN.A GM pota~oes 'OF! the h.istology 0'1 di.ff:e:r~iJl~ mmpart]TjJ~e:[1I'tr:s of ,the rait gu~ was published. (Ewen m:1i.dPl!lJs.ztSin~ 1999\lJJ). A]tllimugh ,t!his peel,,-revrewe.d scienti.fil.c parer wascrHic:i;zed by some, most o.f the criltidsms were 1Hl!pulhlishedpersoFlJlJJ] op:iFllkms. Mio:reover, lTIIl.osl1 oJ the publsihed criltid:mlS (e.g. lCuirer et at, 1999) were answered adeqmr~e~y (EW!,eFl .\lindPl!lJS'ZtSi~~ 1999'][,). Some selected results olff the nu:l:dtkmal! lTIIliJetabol:ic studies wel'e,ag;8Ji!ru;:1t the' w]shes of the .mtihm's, placed on. thewebsite oJ The Rowe" .Research mstiru:~e (w.vw.riril .. sa.r:LS!'C.uk},.vhere most of the work was d'One' (Bucbbum, Aben:l!een, UK}. Hm:,v,e'veT, so as not to jeop:lJi['clhlze their evenmal proper puMrC3JlEiion, 'these resu]tswHl on]y be mentioned h[·l:eHy.

YOlillli& mpl.dly gJ)owing 1:a:~S (sta.rtiintg weligtl!t O!f84:!1::: 1 g) were strictly p:S!i.[~fedolli. iis-O-pI'ote'irnc (60 g toi[r;lJJ1 rrlY~eln kg-I d'iett., lTII~O~~ of whi.c!h was fmmpataJWes) and ]SO'-CaJIorrc diets (11F! mntms~ tolhal descri.bed 'inKuiper el fll" 2QO(I) supp~-eI!l~.en'lredw]1iu vitamins Sind lITE1I]nern.ls(ol.~ 10 days. l'heteS't dielscorutBJirrnoo e:lilthe:r EaW or 'bo]]ed GM. potatoes. The 'co:rn:ItrD~ dre,ts cOIJI.,tamed the Sl3Jm.e arnOllm~ of pa[ieFllalm:nlepota~oes (ra:.vor bo.iled) alone 01' supP]e'm.el1l:ted wiltilJ GNA a,t the same co.lJlcenilErS!tron as expressed m. tirte GM pota:~oes. A posiJti!ve co.IJltl.jo],g;rour oflCa,ts was also irrndlITded m. ,the exreriment:_and t'hese weJ.'e(ed abcta.lbrn:!llli.nbased. high quaHity contml di.d to ch.ec.k ~o:r any potent:ial proib]ems in rat behaviour an.d. expeif]menrt;lJJ~ con.diHii,olJls. As F:lJiirl'!: O'fthe numt!l,mm[f meif;lJJho]ic ev.a]ua,'ttion, samr]es of stOEll,acli1, jej1!J![1i.rn:!I~ Ileum, Ca.e.ctJliTJil and colon were t:ali.eFl,filxoo aoo. ~tam.ed. with hae.ma:taxylm sndeesinIer flITll. quani'lEIitrail1:iv.e tui:sto,]ogicalevlJJ]lI.l3Jti.oF! {F:igs 16.1.., 1~i2 and 1~i3) orreacted with 'GNAall'lhhody ;8Jnd subs:eqllrent1y Sltam.oo. l!]sing a PAP' {peroxlidasf!"anltiremxlidase)1 meillhod. Ito es:ltS!b]isiF! whether any GN.AWlJJS bOlll!l1iJd~o the epiil'.hela] surface (~ig. 16.4). By measl!l!il~m;gthe mueesa] thickness of the stoNl~ach.alFIJdl the crypt length ,ofth.e IDl'~es'li.n.e3 (E.ven :lliiJI,dPl!lJs:ziI:ta!l~ ]999a)i, itwas shown 'Iillrua't p[\O~iJern.t!I,onin ,the gas'rnc mucosa was :iFl! rad causedby GNA,th.e gene producliL However, ittte' goowth-promoiltiFl!g sti.mulus on :the sNl~am iilJl~es:ti.ne of die~sco:rnj~;I3!i:rung GM pol'atoes ]eadmg to ,clj'[pl enl!al'genlelJlt and a part 0'1 ,fie' sto]lil,acheFl~:rgement was not a GN.Aeffect. As sh.o\!\!'!FI before and contiiI"mM here, thEre W[lS ;8J &l!:iglht binding oj GN.A ,~o the s.maUinrl'.e.s[iFl![]]epHh.elii1!J![n (Fig. 16.4,). HaW'ell,el':.. GNA ]S[1l0~ a Elili~otic lectinand dle:refure it diid notin.dllilc.e byperplaslltic gr.awilt.h iin dos ItisslITe (Pl!JJszta~ et ,I}I.~ 1990). AClJOI~rl)ilJlgly,~he .~ejitma.] g:;row ~h.was prdoalbly due ro some as yet unknown effeGts of other p:lJi1:'i1is of the genetic cons:tmd used rOT Ifte' t[ci1lF1!slOI"[l];lJJth:m or :the genetic iltr<l!J]stoITll!ation itself. HypeI'" pl,:1s~awa~ shown p])e'll~ous]y by measl!JJil~iil1lg theincrm~ Ern myrtl.elJl:gth (lEwe:n Sind Pusatai, 1999a). How'e'v'eI', similar resu]ts w,ere obtained hy measuring tiheil1l.ITe.\lis-e m. clJ'Ftc.en numhers (Table 16, nand cry]J't EliltHolkfii:gures (no:t1fuUy s:i;gnjjficaftt) ]ll'I the ~ejitmum of GM poboo.-fed mts (TaMe 106.2.),

A. P:usz{ai et al.

lb)-:

~

Rig:. 16.1. Comparison off tile stomach IlIl1UlOOS.a off rats fool w'itil raw GM potato diet" (b} shows markad [fiicl:elli n~ du:e ro hlV'pe!trophy of m ueosal ce!llsi n ()ompariSOlfll \l'l,<i~ that ![)~ mrs give'Jlllih:e IP are ntal 'I ine (a) (lllin = 1 00 JIIlIii}.

The results sugges:tedthat it liS poS!S~b~e II:n.lJ!t crypt hypeIW~.lJ!si.lJ! and . anincrease in epithe]]a..] 1r~ymiPl:n.oc:yte iir1I.fU,tTaJItiDnohsenroo. wilt.h GM. pata.,tc!oes miJgllfut also harpeFlwHh ather GM. plants Ij'ha~ had. beef!! deve]Dped! l!.]si:nglLhe same Dr s~.mi~m:gene:ltil:\,ffrorrs and method of insertion. :n lis thereloire impel:a:t~v,etl:n.lJ!t the eJkohs onthe guilt structure I]Jnd mJJ~.etabollsmof all GM l:WpS soouM be :i.n\'est:iga~ed Ihorrou;gh.lyas p.art o~ tine regu~.lJ!ID:ry prOijJess before theirrelesse iin:~o the hl!.]Fl~.lJ!f1.~oocl.d]a:in.

Desiree andRl!.]Sse~ Bll.1:1bank pOI~.lJ!toeS exrressJrntg [\,He:ITIlIilnaly m.odi.l],e,cl CffI'opllrld]llLe.1.iiltiln CllItrornc peptide chimeras and. eentrol Hue po:taJ~Des Jed Itto mice caused severe weight loss, 'Ute 11J[]l1.Wl.ds did not goo'l\V even a~teil." su!pp].ementiin:g ilttese potat0t.'8 wlithroo.ent ~.lJ!borlJito:ry chow. hccoooiFl!g to the authors (Osu:sky ret al., 2.000), mice fed w:itih tubers fro'Hl tr1lns~e[]lk pota:~oes were as be.lJ!]tihyand vlItal (sic) as '~h.ose from the control gI'O'l!.]r, and their fuecid pe]~,etswel'e CO]1l1Plli:rab"~.e.

Howeve[', ,!!he' s.ev,e·reweighl ]OSS serious~.y called. m~o questlon thevalue of the' resuhs of th.i!s po:or1y d!esl;gn.edfeed.ing exreriF.lJLe[]lt

IFi:na.1]y,;m limpo:rmrut stl!J.'dy wi1uve t·o be described eVeJlth.ough it waSlJtut pl!.]b]lsi'ted In I]J :reeF-reviewed! jOl!.][-mI]. lmt ~e ideas 11!I1i.d. ,e:xpel:ilmeFIts described had!. :SO]1lle Ir[](fi[uenee enthe &e'VeloPmJJ~elJt:t O'~ GMregJ!l!~lrion (No~eborn et ,:1l" 1995), 'Ittus, a new ].,:100[1]tml' GM~omaio~.iFlewas devd.oped l!.]sing the B.~h,lu',ing·tellSis crystal rm~.ei.n CR¥JA{b} gene but, mtead o'fthe 'CllIu~HIO!wer mosaic virus 35 S promoter (CaMV 35 S},wJllich. Is used :ilFl! pmcti.caUy an Ifllirst-genemiltiioFl GM mops, a pO'~lJrl:iaUy safer p~nl rW]1I~,ote:rwas used, .Ah'.hol!.]glli1wiilr.h tms fiheEli:p:ress~o:n Ievel of ,the Bt tmdint was on]yabout 1. 12mb ,of fihaiiI TOUlFI!d with Ca:MV 3CI S/th.iism]g~t be iimrroved urOFl. in future. In iCDFlh:ast wi,th ]1I~.ost o~h.er studies with GM l:ro'ps,th.ere 'l,<VlJiS a

Fig. 11 &.1. Histology o~ tha j!i!j!drl!1Jm and ile!d nm of rats {edl raw GM m p3l'E!nt pataro di·!i!tSc Jej!1Jrl>a.i crypt lengtn and >rells ~.hibit marked eiflll argemen[ afw. feedi ng rats eM potato die[5~or lO days ~b)i n comparison \-.1th tl1.ooo of rats gi·ve-n p.alrE!nta:1 I ine potato drets {a}" rile vi lIues lein1?;th is si I'll i I ar in [both, but inlir3i9pith!i!lial [lymphocyte cell COUII1[5 appear to be lncreassd on [Ihe eM potatn diet In tneileum, both crypts and villi oJ rats on CM potato di;!i!t!> alrE! elollga.te>dI (d} ;in cornpanson witn parent potsto-fad rats {c} {bar = 100 urn) ..

364

A. P:uszlai et al.

i(d}

Fig. 16.3.. The fllu:cm.a of the cascurn OOmoostrate!> little cha.n~~. [[!litre-renee!> betl.'leen GM-Jed (b} and p:nelll line potato-fad rats {a) are slight, whii le~il.e colome I'll UQ05a. i s mooerately thiclienedl in GM-ted rats (d) compared willhl [hat '00 rat; i8;~en the par,entalline 'c} {bar = 50 Ilm)-

365

h.' ~~:.J~~~

Fig,. il6,4. 1 m IliIUlllocytochef1iiis[l)'o-f the~ej UIllU f1ii o~ rats fed' raw GM potato di ets. fa, 10 days (a) shOVl'!S Imooer,ate binding of G NA 00 viii U~ tips (00 r = 50 .!:I.m}., Simi I oar binding o~ G NA oo~eJulllal vi II us tipsls

fOUind' in rats gi'ven p.alreillt pctato diet supplemented! w'ith. GNAirl amounts equivalent ~o tna:~ e:qJir;e~ed ilf1 the GM potato (b) (bar = 1 00 !Ilm)" SeatiCJlJli~ were Iii rs~ trealed' wiith ,alllti-GNA rabbit 9.Flbibody {dil U[Ed' 1/100}, fo I lowed! by visua I i zatiol1wi[Jh PAP., Note the5trong, anti body r,e,adiviity of food parliic las ill the sectiOlniS.

1!!If

/111 r :

.

J' •

/.. /~

,""" :;i,,~I.!L

) ~ ,~ '

~,j'

I.

". ,'.' Q' (

t·.'

... ,. ~.

jI ".

Cliiet

Parelilt ViS .. p'EI[llmt+ GNA(~

Parent

Parem+ GNA

Paneliltvs. ~ral1lsg;ellliG {~

Parernt+ EiNAV.5 .. h;ansgenic

(~

Raw IB!lJliled

Raw YS.. tmiled (p)

OoJJS7 Oo.46!6

OJ)OO 00.769

~5 .. 9 (00)5) 0' .. 8 {1.1) 0.006

117 .. 0 (OoJ') 118.2 (00.2) 0.003

2.0.3 (0.8) 18.2 (11.2) 0.0013

00 .. 000 00.749

"TIme II1IIJJ moorr oJ mJlJlei werr€ caLiIIiltedlseCjueliltia:IIV on we llhJmielllffid hasmatQxylilil alild e!ll!sin Ipara!tiilll seotlens {4. ~m). Values; repressl1lt means (so)forr5ix rnNi; per t[eatmelllt; ten orypts perr [at were oolJJnted .. Cliifferel1l008 b etweenlrearlliillBlilts arre signilic.lInt when P -c OJ15· (Sludenf's tteE't) .. The e,ff~ecl [If ooilirng

(P = 0.75!9) is, ,11I0t .sigl1liifi'cam:, \I'~hil:e !halt af GINA ad:ded Of as transgene pradUc,t {P= OoJl19) andlhe eHoot 01 ~ralilsl\[lJmati{l,11I (P = Oo.OOO) are higl1lly' si:gliliRc9Jlilt The inrl:era:ctiQl1Is bemeefl EiIliJA and cookingl

(P = 0.043) al1ldllbeMeelil~ralilgl\rnrmaJti[]in and oooking (p=: 0.0118) a[e aJI'sos,igrniificanl (1iiIlulitiivar.ian1 alilaJliysi!s: with "fllk'eV'SiteS.t)"

commendable aJ,1BI:emr'~ rl'D rneasl!l!iJ:'{.' the- binding af: the gene prodllrct~o the TaJt gut :!mdace :in u.ioo rather I~ha.n. us~:IJIg spuriollJS argJillmenJIis as to why '[fuege:ne prodl!J:ct should not bind,

A.]1ftough [Ito irn 'Di[!llI b:iFl!dmg was fOl.ilnd, tWs shol!]]d DO't detract .f:mm. the :siign.HicanJJe' O'f this i.niJt:i!atl.!i,e beceuse, due to the lack 0'1 avaHa'biliilty of 8l!l!flicieFIt q'illl!rulHii.es of: Bt Itox.iirn

l-a~~!e 116.2. Mi:tooo Illlumbe~s per 1100 CIiYiPls illl Ille j:ej,ulllllllfli oIlr<1tsioo potato di:e1s.'o

Diet Parent

Parellli + GINA TiE:lllsge:lllin

Aa'l.!i!' 43

l8ioiloo 57

4!9 75

56 157

lselated mom 'GM. tom;atoes~:,m E, coU reoolITllblnant and. polentii:lUy Ies:s silab]e farm of :Il.he g'eFlE!' prodlllJct was used :lilll! the il?xper:irneFl!~, and :I'irs pos:;1!b]e d!eQadatilon m. the gmt mll!y have aeeounred .. (or t.he Jack o'iibindmg, However, Btioo:inWBiS shown by ~.mm1ll'locytDCh.em.ilst[)' to biind. :~D gut seetions, inclu.diirl]:g I~he caecumand oolen, fro.rn hlllJT!lll;llJru;: and.rheslllJs monJ;;,eysin vitro,. Unforrunate]y, t!heiill~ s!hon:-liel'T!ll IDx.kitytesting In mice (a!lJId l'aibb:iitls) <lind the irn vitro siilITlilU.1aJed prol;eo]ysls:lssays, w-ere also Ca!n:iioo. out W:lrth. the IE" mlf reoomhiiFl:l3JfI!l gelJle product and th.e[Iefafe thelr conclusions of firlJLd.ing::1JLO ~oxiic ,eHe.cts may not be v;aHd,. OJoFlllmencbhly, the alllJilttors carried out 81. 9t-day(eed!m:g smdy MllLh [<ltsl]Sm:g .lIDeeze:-d!rioo GM. vs, p<lirerJ!t line tOlITl1l8Jitoe:s,. whidu were Included Bit a to%. level in the d!lielrs, blllJt no diiHeJlEnce's in .(ood! ~.nta~ or body end orgBiilll!wei:ghlirsweI1e ful!l!lJtd, However, because the Bt to:(Io;in exrress,tOFl! level in 1I'he wmaitoes was Fo.v, the ,dai]y ~nta~ oJ ilihe gene prod!.l!]:ct(s) hy the rats was ids-olow.,. Moreover,as tlhe dai]}' iFlipulf of ~mIl1l8Jro Fm~eirrus was on]y lJ!bolllJiIt 5-6% o.f[he ~ornl d!iJe<~;S![-y pmilte:in intake o~ Itthe :rats, i:t was sOll!lJ~ewl:!t.lJ!lopt;imiJs:tic ~o ,expect any signJifiicanl ,changes iilllJ~hese numJttioFl!:l] p!ll![-ame~ers.. To have anynasona1b]e dhllllnC'les to 8hmv ur S]1I1lB!]1 diff:e:J,ern,ces lin t!he mrtrilt1io:nal. value ef 'GM V'S. parent ime crops, :l,t wooul.d. I:!t.lJ!ve been impo!lt<f1Jtt touse as high a poolelin cencentratien BiS possible such as It!ha~ in the UOc-d;llJy G .... , Fo:m'lto~eed~ng study carried OUj~ at The Rowell llil!80'ttiiliu:te~inwhkh the GM pmifcin in the d!:iJe~ w.as diluted ,only !twofo.ld byot:her: dieta.ry pro1leins, a!ID1d. thisaUowed!. the si:g[ufkant d!:ifie.l.'eflces in !h.e gro,wth :r.a~es ef [;all:s fedJ. enbsked 'GM. potato diets vs, P&l![,erI!t potaro diets to showupvIn fad, toequalize th.egwwt'.h mtes oil the mtson th.e GM potak!oes~o tha.t of theaoiJJ:tJ:.ols, th.e GM

diie~ Itmd!to be supp]eFIleFl!~ed!. with an extra 12 g Iactalbuedn kg-l d!±e:~:. and It!hi:sex.tm pro1td.n gBive lJ! qlllJanJIti.1!;at:i:ve measuee o.f the dH.(en~:ce Ol~ ,the Iliultr:itianal va]llle heh<veen GM and. nOFl!-GMpotaloes, EvelJtaJt I~ese sim]~ar grow,th mt~, rhe1,\v,elgh:ls olf some of the rllJ'~' v]ta'~ ,m:garns, such. BiS the guf and padicu.1acly tihe ~maU mrestine, ,the liive:r and kidneys, were s'ti.U sigrn.i:ll.cant]y d.i:IJe:renJt.

I-nere welle other orniLss~.a1JlS i:ntbte B~ wma:i:,o study,l:hemost llITlllIxdanJt of: wh~.c!h was 'lI:mt no 'Iil~ toxin survivalwas measured lilll! t';he guj~ luru~en IlFld. rto .gild h~st'Dlogy was done to s-ee H ilihere was any Ell' t,:OOi:~.n bi:nd!iing to oe possible stl~ctura] dha!FIg:e<S :in il!he gl]:~ epHhellium orwhethe.rlymrhocy~e :lnfitmlion. occurred. "[h.is orniiss~olJl. 'is par.tiicular.Ry h!llportanl' becaase ]atelc stllldies sdrto.verl ilt.ha:~ ~e &]]:f![i.1aIC 5t it.oxm CrylAc could bind to gut ep'it[heli;a] ceFIs :lilll! l!1Illlce (Vazquez PlJ!d!:roFl! et at", 2ijOO~b) a!IJt.d.incl.uce mucosa] an:tigeruc sem:itizlJ!tIoFl! (Vazquez Pa:dl.IOFI et Ill., 1:999, 2QOO\lJ!,h}, The aUe:r~ell1!ic potential ofiH Iltoma'~es was n.oilt in"E.'sl:igatOO. e:Hhe:r,. However, desr~ie SO]1~e af liPS snm'bJOl!1l11mgs, ,this study ShOWM. m:lny novel <[[ltd!. COlITll.me9J1G.ab1e .f,ea'tures,.wh.i:ch_a:her SOJTJJlle iJmpmveme.nilr:s, may, hopefuJ!ly,iJe: inemporated into 1ihe ge:ner8i] GM fuod!~es;ting p])(];Coomes.

.Allf'rgelillii!i:iity

One of the major he:lJ!lth conceenswith GM .(ood~s its po1!entialto~]]crease illIl.le:rgllies :lilllJ the hlllJmmn popu]al:;ion th.rough the Jood mllm.,. 'Itte po§'S]biill.ity of fatal an:lrhylm~ :lilllJ semitized mdiv:iduals 8ifitter iliheiJrunwittmg eXip08uTe to aUergen.c proteins In unlabelled GM food!stuffs lis lJ! real dailll!ge:r,.When a gene Is transferred from a soueee oj' known lJ!Uergenc po~eilll!til.a], the aseessmenr of the lJ!Uergen.city o:f the GM ,crop iSlJe[:l,tri.vel.y sUai;gh:~fOl.war.d.,. This can be done usiiFlg :ii~ vi~~ro~ests wifih sere born mruv:idlllJ:l.ls sem:ihzed.~o lihea.lli1e["gen.f.oornrhe origflJlBlil. source, Si.mii~;llJdy, it :is relBitiively ellisy~oasses:;;: the eUect 'ofgene:t:i.cel1l:gin.eering 'on endogenous aUerg'em In C['O'PS w]t~li so,]1I~ee'l.':id!ence Qfal]e:rgenkHy.W:itllilJ tests such as '~e radioalle:rgoSlOlCbeFltre!llt (MSn RAST imib:i:tiooFJ!

367

end ]mmulJtO!J1oumg. the aUer~e[]ti.c pa~eiEl!tillli] of the GM 'Cl'Op lis ea,S,i]Yil:lU."llisured .. , There are now SeVl?ica] e:XilJJlTIIllp]es fO[· these.. such as the d,eJTilCmsb:a:~kml of the al.1erg'enicityof tihe BmzU nut 213 seed !>Jtm;a:ge: prcde:i.n in heans:gelJl.ic soybe.lJJF' {N oN!]ee et al., 1996) or the cod:l1sh ilJJ]leilcgyin poifuJJtoes gelJle~~,cally ,en:g~,neered with, cod p['ot.em gelJlesro lTII~ilJJke tihe POlta,roes ~olel"a:~e cold, !>Jto:rage (B:md:slJev[ensen and,Pou]selJl." 1997). The cbiim thlllit in glyphDSllJjte:-to']e:ra!Jll~ soyibean il'.he mtroolLrctnolJl of the he:J!bi.cid!e resistance gene does []lot ilJJHi'Ct !She aUergern.city of the soy elJld.ogelJl.Oilll a;[~el~gensis ilJJbo a good ex:aJmpIe (~nrb ,and ~I.I.CJhs, 1995). Hn:llFlg shD'V!IIT"I irl] a su["V'e:iUaI.Doe prog[;i)1!Illme O~ful:m:l"VOIlcers before and .4ire[" exposure to E,. thu!"j.l~gie'~'l8'ispes;ti.cide sprnys that: some developed skID §e1JlSi.tiza:tiion ,and [gE antiiOOdies to t'he Bt spor-ee%trn.d atrlidtha:t bVQ of il1.he'llJi1i. had a posi:tive sHnt-p:r:i.ck tesltt,.H may nowbe poss'i'Me ~o '~est JOilc 'tIJie allergeiJi:idly D.fB11 't'OO::IlF1S engineered in~D\'ariDilll crops (Be[nst:e:i["l e~ al.., t999). This ]S all t:h~ more :i]!!lpartant'bec'1l!l.I.setbie CI'}'lAc toxin has flOW been. shawn. to be a potent am] :inllMUflogen and. ilJJaJn\'an:t {Vazquez Padron e.t til" 1999~2.000I3J,b).

It ]S much more dHf:lcuJI:t to assess the lli~l.el·genridt:y of GMfuods when ~e geiJie is 'lm;n&tel.~:red. b:-am a p1ant whose a.l]ergeiJik po:tern:tial is uFlln.own.Moreover, :i,~ is also pooslb]e thall!, as ar-esu]t of ,the gene 'tmnster 01." vector I:lJISemDFI, a new allergen is deveFoped. orthe if.'xpresskm Fevel. ofa ginor a"Uer~en is increased ]FI tihe GM. crop. The gene pmdl!J:ct can also havealFl a]]erge.n±Cadjmrl3Jrn~ eHect on ilJJ {ood CDF'llponeJIl' pr-evIously of 1aw .aUeFge.ni.c po:te:lJltiilJJl air som.e cornpaneniti:rn. tihe GM {ood F'llLay hl3JvealFl 8Jdjruvailll!t e.ffed en t'h~ lli]l.el:gern.cil~ of ~e 'ttrarrnsgene produd. Un:rormna:t'e']y~whnetl:ne:l.'e' are grnJd aruma] models {O[~ nUlmitlDFla]/ l~ko]ogka'l testing.. no safis:fai:oo:ry arulTIl~lllil. ]1IliJode1s have been developed so tarffo:r ilJJ~l.e[~geFliidty tem;ng (Helmjmd Burks, 21(001), For rth.e 1t1:mlle bemg. orn.ly indirect me:thods ll!l"'e a vailable ror ;~he assessment of the ilJJll.ergeruc pote:lJlliilJJl of GM foods de:r:ivled (['OF.ilL sources off unik:nawTlll!Mi,el'gen.i:city. There I3Jre a mneber om recommended app150adFtes '~o be fo]~o!ioved, .A use:fu]p1'elill1ii1:1i.13Jq &~ep isto eililtab]ish i.f '~he:re <lire aFlY seql!J:enGe h.Offio]ogies in Iillle iI"rlli["lsgen:ic r~iotei;n to ilJJny oJ t'ne gboul

200 mowiElIa]]erge:ns. mrlh.e:rea:re, ~n v#m tests far .]giE['eadti'lllty needto be per.formed.. H ]S ,t.hought that the peptide 1eng:t.h in Illte !transge:nk p]U~in!iovhkh isoptimaUy needed for b:iinding iB-ce]~ epi,mpes[iequ]["esthe ;!).[;esence olFatleast d;gl:doondi:gu.ous identn,CilJJ~ Dr slIm.i]ar amiino acid.s .. However, ,the alTIl~.i.no adds ]["1 '~hea]l,e~:genk epiiiIDpes l3Jil'e[ca.rely mnt:ig:urol.l.!>. M:orem.'er, 'lheabsenGe o~ a pos.i,Hve reaction i1n 111'1 i,i',ilro testm;g does noigJ1ta.l"a!JlIi,ee !tlhailt ,the 'kaiFIsf,eI~red protem 'is nol~ lJJfI ,al]erge:iJL In a deci.siioFL.-mee~ypeof h~.d.ii:red: apFI'Cl.acb, ,the :IJIeJ{:t s't:ep iis to CDnsiJder :~he molecular size, glyoosy]a:ti.aIJi, smbilUty, so~uh:iljjty and. isoelectric po:i["lt of th~ t:r.a:rusgeFl!nc protem ilJJnd mmpa~el:hem ....-ith th.ose of lnoWTll. ilJJlel"gens (O'Ne:i] et IIJI.., 19'98). Un{mihLJJmlllJJite.ly, in liIl~O!litt slnd:ies ['0 dlllile, IttheaJ.-irmpodlliFil siabaiity olk the trilJJiElIsgenic protein to gut P(\()tec']ysns ]S established inan i~l Q,ilro sl.mullllired. gasl1r:i:c! mte!>Jti.nal sys.tem (As:twD()d el al" 1996; M.e:~CilJJllfe et al, 't996), and.lttMs ]sfnndamenlaUy :Ilawedl.. The [iesu.l:t:s" ItthemJore, are llilttbesl~ rumsleading and at worst' e[lIiOneOI.l.s, .R.el:imli.ce on. 'theoo.n~ert -t"!:mt moot ilJJ~l.el"'g:e:ns. are abundant PI'ot:e.1.IlS is rmbab~y also n~.islead.mgbeca:l.iSe, :fo:r exalTIllLp]e, Gadcl, :~he ]1[TIajo]? aUer~en m ,oodfij&h,~s no!tt a P1iedo]1llinant p:t'olcin (Bmd:slJev-leru.e:n and Poulsen, 1997).

Wne:n ,the gene JlespoIl&lble fo!'" lheaUeFgen.idty of a crop ]S known, :its d.onmg ilJJnd. :o.:eqlLIenc1iF1,g open the w:aJY Jm· its :redmctioFi by an1ti~ru;e RNA. st:rall"e.gy. Thus, ilFlrice, the 1D'w mo]emlB!r wei:ght a-amy1asejlttrypsJrn irnhjbrors ll!re maj:o:r illi]~['gen&, .A pilJJ['if olf the genonlll.c sequence: encoding du.s p['ote:m :I'F1! aiEll antisense d.iin.'C!tlDFI was oJnstrl!J:c~edbetwe.en the- P[log.o:~er ()i~ the rice allergen geTlt!e ll!ill1d lits waxy teml!~.nato]',and trns ·.VlJJS mtl'odnce:d mto rice pmt.op113sfu;:, The' ilJJll.e.['gen~.d11y of the regelJle.ra,t"ed p1an'iI:s was s.iign.I]'Ca!JlIt~y Iess then that of pare:lJtm]wi.ld-type ri~e (Naka.mum l3J[]Id Matsude, 1996).

In eonclusien, allergelJi.idty testiilJlg appears to be one of Ifte Affimes hee:]s of GM food sarety.])tt is deal: lhat~if and whenH ]S known tlr!at the P[iOte:iTl gene ]S derived from a source witlJi.ll! history of aUergeiEl!~.cirt1y, there is a reaeoneble lIJe])~llliilJlty it!hait t'lhe GM cropm]] be allergenic, UIJIJortl!JJiI'llllItely, the reverseIs not !!:rue: It!Fte use ofagene nom. sOliIllLetiM.ngthat ]s not ilJJllergenk ·M.]] not gul3J[oa.nt.ee Ithal '!:he GM

3M

A. P,tJ\5zl.;;ii et a L

cropw.ill no't possess alel'genicity.[nllihe absence oJ new and reliable methods £O!i .id:eq~e:nki!:y testing.. pa.rtiku.1arly the' DilCk ,(]If g'Oocl anJiElllllllll models, at pteseflil it lis elmcst impessllole to ·eslilllb]lis.h de.l]u]teDy whe'ther illI. IM.'W GMC[iOpl.s iIJi[~e["geI1!k: al~ not JJ[]1advllIJ]ce ef itsrelease m~o the lnu.ma.nla.mma~fOOt:!<!:lIf,eecl chain.

OIn.e has to agliee wit:hth.e opiFllionexpressed in Science {OmITtllmgo, 2!OOa} ·thiIJil t:Fteife are many opinh:mts but vel)' .lew data on '~e ro~eIl!tiBl] hedlr.h. risks of GM loods,. ,even though reseaech to ·exdude su~hl.~.sb should have been carried ·oui: before t[he GMcrops 'Ilvel:\e' ]l1l!t[1odi.ucea inlto the food chaJin. OI!J!ii present datsbase is therefore w1oe'm]]y inadequate, This ]s dearly seenfrem iIJi closer ~mtm.y of the reference lists oJre;:eIl!t [1Eview'S which conta:m .only iIJi tuandJil]1 oJ tm:.iim.lo,glcal/fliutidth:n:m] and. immune studies (]If'GM Jood.coops Fubli!shedin peer-reviewed ~i.·eiJtce journals (Ru]bal-MeIl!(Uela ilJiilll!alLi.nns, 1996; He:1':z et(;ll., 2000; Kuiper fJ ai.,WCIl; PusztlJlli., 20m). Mm:eov.e:r,the sdenil:Hic qll,a]jjty of even what iis pub]i.MtedlS:, in most instances, not lll!pto the standards tlFuarlt ought ~o Iooe exrected. In d:1liis review, data. publishedIn peer-reviewed and some lJIrn:t-peerll'evi.ewed journals have been examined in detail How.eveI',as our future is claimed to be dependent on the success or fai]mie of 'lLhe promise o:f geneiltic modificatkm ddirvering 'GM(oods w.hich wiilllbe whal.esoNlJLe, ple.nrttifu] ana, most i]]lnparlant]y, SlliTe :for us aU,lLhe emphasis was OIl stirict burt fail" cri,tids.rn.

~m]Iln iltheresul:ts, i!!he conclusion seems lm.osCilJitpahle tiha.t the. present crude meshed ef genel:ilc modil]CilJifionoos noilt delivered G ... 1 cmps that aee preaidaMy SaTe and who]esmue, 'f'ne promise ofa superior seoo:nd g'eiFlemtkm oJ GMcoops ]8 still 'iilll! the future. ]:ti.s passlblet1hart some lofthenrst genemtion (]If GM coops m<l!y supe:r.fil.dally satiis:fy some ,oomElllle[idlll end poi.nts, such. as tlFteJr use ln bm]]er ch.icken preduction, However, w'e needte censider ithat these GM ree.a[<1tion-fea animals evenh.liaUy wlilll be COIl!SU]]lM~a by

humans, .and t:Ften~ lis ilJib801ute~.y notl:1liing 'known aiJoocrt the pa~eFl1tiBl] hazards (i.f any) fOI~ human he,ab.h ·of iI!h~;si:l]diirecit exrosure~o GM 'ooa. Furthermore, theexamples Enth,e papers hlgh.Hghted!. some d'ir.fe.l!eiFI:ces even between such crl!Jide thin~a8 ]1Inacll'ofliUtl~,e,IJi~Qomrositio:n. o.t'GM. end wuvenrtti.ona.] ]iiJJt,e,s. It :isill'g;mea by some that~hese di.f:lfer-enc~s have liil't~.e hiologk:al meanm.g. However, it .. Yil8 dear tha:~ mo.sl GM and p:a!ir:eIl!tal~i.n.ecrops wouldargu.ilJiMy fam shod ()If the defin]trolJl (]If 'slibilJmrun'tia] egju~va]ence' .. This Cl"I!J!a:e, pom:Dy de:.ooed.aI1l!a Wl!SdeFUti.filcccmc~p't ocrlHvoo :lits posslb~:e previDUSuseliu.ln.es:s. There iSaFU ur~entnteea to com.eup wi.th Jlove~ scieFitific methodologies to pmbe in'~othe composi6]anal... llill,k:it±oIllllJ]! t':(lKi.cologicaland ]1In.eta!bo~:lc difterence.s het~efIJ GM :md cOFl!v·eIl!tii:ollU3J~. crops ]f'llveW.i1lFUt 'to put ~his t.eclmo.1ogy on a pmFel~ sdeniltifk fmmdaHon aoo. aillsoto a1]ay the fe.ll!j[cs o:f ilihe genera] Fmb]ic. Vlre need. more science and not ]ess..fim"p[iOper safety assessment, our 1].I'S~ oo:n.cel9FIJougifrut ro be ilr.oestabHs:h. an a case-by-case basis the ]ElIlpad oJ eomponenlrs o:f GM !Dodson the diigestirve systeEl~ iJfus sltrud1!J!Fe andmeiabol]s:m, because the way our body wi.ll [iespond ·to GM fC!oC!odswm be. p[:ooeter]1lllmed atthislevel, A'OCOf,d:mgto ~eRoy.a] Soodety ((999). weneed 'to refine the expe:rlElinelltla.] des.iigFI of the reseiIJiJ:ch. done ·to date'. New ideas we[ie also ad vocated iin the .i!:ii.ru..et d.e!b.aite fEweFlllna lfIillSZta.ii, Th.999ib; If:(JlI,iper e~ 1iI1" 1999)1 and. at the OiECD Confe[iel"lcein Edinburgili1 i:nfiebruary 2000.

IRel1:!lDlnnllnelld<lJtiolHl

MaJilli1l tasks and lm.ell.(ilds· 'for safelty assessl1lelllll of GM nl!l-IPS

1.1.. For composttional iIJiI1liIJi[ys.is ana comparlsorn.,thepa:reIlit andtr<t.ns(or]1ln.ed ]imes ml!]S~ be gt'mvn under ]deFIt:i:CiIJi] eonditlons, t:rell!ted and harvestedthe SilJime\.yay. In addition ~o proteins, s:laron,Upids, .etc. oJ the parenrt end GM ]Jines,. their contents of hl.o.adiive comparllenlrs should alse be compared by noveD. metheds (pruleoNllti!C8,nngerpmtmg. etc.).

2. 11he sfabiiHty to degradation by acid. or pepsin or olther pw~ease8fhyd.ro.1B1ses of GM

369

products, foreign DNA, induding the gene construet, :p:r-arno1ter,alrltjibrotk resistance marker ge[1I,e, etc" has '1)0 be eSJllablill:slrtedl lin. the slDIIIlLacih and. ][l!~e5ti.nes olj rnoo!el.am.mals :in (,I,ioo.Willih GM Iectiin:s,i.nduding B~ 'irox.iJ!FI, the p[ieSelJlCe I absence of thel.T ep'i,iilietl,a] binding shouM.a.]so he demDru;h;arred by i:ml1lm.l!J!!Fto.hjj!l'io~ogy.

3. ThehiJOo]ogka.1, l.Im1I.ml!J!£1I.o]ogical.h.oITl1oIlll3!]

properi]es and. aller liciltty (]I~ GM. proo.uctrs

mUSJIEbe es'tabl~:sh w:iiiththe GM p~:odl!1ct

isoblted '&"00]]11 !he 'GM. cmp, a![1I:d nD,t w:i1!lh recomhiJilllllJJmlJls &om .E roU, as these twOo may have subs;t;mtia]ly diJJHe[ie[l!t pl."oreIilties.

4:. .As GM. fucd isun]]ke]y~o be Wg1~y poisonous, 'IDxrcHy' is alrl l!J!irJ.!Ie.1rfu] concept :md d.HI]C1!J!]t to asSlJJY . ln COOF1Jtn.'a:!l't,. DlUtrit:i:OF1Jl3J] sll!J!dies in which GM erep-based die~s a!n~ .£ed to youngg:rowmg aruIIl~a]s shol!J!M reveal their posslb]e har:mm] effeclrso:n metabo]jjs.m, organ deve]0rmen,t_ !immune/ endioc['line sys:t,ems snd gurtt :Ilora,whlch. rogethe[" det,eolii:ine the saJe'ty (iij li!he GM c:ropaFId~e d!evel.opme[l!t of the Y01ll!l:1i;g Inwhea]l:Fuy adults,

!i. fen· anirm;al. testlin:gi:so--pm~eiruc and isoelli.erger[icd~etB need to be formulated in wh.kirl most oJ the- d:ie't;8![~y prot,:ei!n~s die[;lvedfu'oHll the GM c['op" Theoomposi:tion of: the eenteel die,1ts shouldbethe same :lJJslhe GM diet but eontammg the pa~ient: Eine\<v:ith. or M'lI:mll]'~ slWpplementa'tio:n.\<v:H.h. the iJso~ate(lge:ne' preduet at the samelevel asexpressed m. the GM ]line, Groups CiI.fani.rnals (fiive or more per gm,up), of si:mjbr weight, sh.ol!J!]dbe pajJ]:-ted in sho])ta!1li.d. ]oFli,g~terme:xpe["lmen.ts. U["il:1JIe and lEeCillJ] samples should be oOOlloo~:edfur ,the del>eD1ti.nation oJ net pwt,eln u~lilzlJJtioFl fNipU),rub?ogen balance and feed. utilization :rat1:os .. mood samples s!hou~,d be taken before, duringand ;at theend of ,the experi.me¥lt5 .for :i.mmlW!fte stlmdles (ie. lymphocyte prolitfe:raltioFl ;a!liS3Y, EHspCilt),lwrmJJneassays (insu]iir1I, dlo~ecystokinm., ,e:tc.} and far ~Jrre deitem:l.iiFllJJf.ion o.~ other blood o:mstJ!ruents. 111e anE;aI.s ;are to be' weighed da.ii]yaFld any abnrmnallties dbse:rv,ed. Afte[~ hl1m:g~ea.1li!mals~ their bodies should. he dissected, the glmt rinsed a!£1I.d.its 'COlliteni!:s saved for mIDtther studies (efI!Z;)i'F!ll,es, GM products, UNA). Sf.\ClU,O:Ili:!l should he taken for his~o]ogy ,and l1he wet and d.rylicvei:ghts oforgafts recorded aiE'ld ;af1!a]ysed.

With su]mMe statisfical a!£1I.illJRys-es (ANOVA, ]]Illulrttir]e IJOl!lllpail'il.wFls ;and/or ml!J!]t.iivaril;aite analysis), the s:igru~.I],C;ll![1l,CE." oJ dH{en~~nces, H any, in the pammf.'tel:s shou'~d be esta.b~~sh.ed,

• If d.Hf:eiLence.s beiMeenan~ma1s fed GM and p;8!l!ent ljjne dfeit::s indicate th_<Jitthe geneltic:moo.i:H.cat11.o:n must heve ha.d a. si.gnJilJc3nt ·eHect on ut~l.iz.a,t:iJJn end flutrit~QlJlal. va~'ue, the 'GM coop' 'CillJmTiD't be accepted fOi" Inclusien ~n 'lite huwmlli!FI/ aniim;al diet.

• If, silmjj]a:rly loth.e GM ,di.et,the p:uen'tt !line d.te'~ spiked with lithe gene pl'Odud showsdif'fe:rences, '~he use OI~th.1S gene irn GM loodlfe.e,d~:s not l3:oceptable,

• Ifnte,gative eHects aile []loot ob~er\,ed with the paIenf mlJle die,t c(]I]'lita.m~.ng il!he~so-]ated gene product, iiltis Hldy l~aiIE the harm is caused by the use af the parf.iCiU.·lllin." C'DF1JSJkudtt 01:" by an Uirlw;aml!~ed. or l!mJO!I."eseeFl eHect ofth.e gene :iiru;:e:rtioon on the ge.nome.

Ammal ItesilEingis hut a first s;~ep and not a subsillil:utefor h!uman st.l!J!.dijes.,. T.f t:he·re ]S DO md.iicarttio:n. of ha:rm to fhe aru]]l~BJ]s,the resultswlll have lo bevaH.dated. w:iil!.h ill!J!Hlan volunteers m. cl:lli1ca] dOl!J!ME!"-bHiE'ld, placebocO:l'1itroomed drug-'type '~e5ts.. Sl!J!d]. st]1d~es may have tD go on ro:rcolli:!li.dem:hle FeFlgtihs of 'tl.me. It must also be ~p~ ]!FIlITl1l.1nd ,that ;aFlY pOI~elJl'ltia'~ ha:nm. W]~ GM food ]!Il,ay be ]]llO:M aC1!J!rre lin. theyolLl!ng. eMe:r1y and sick. pa:rtiC1!J!]a:rly those SUfferiFlgkDD fml, hefatiti.s or oith.er viral dis-eases.. Many peop~.e suf!fer &om ;ame~~gies and other diso:rae['s of the gast:rointestilna'l tract, alJl.d. :~or these ,the CCinSl!J!Ff~ptioll of GM food may ha.veunJm)esee¥lcoIJIseql!J!ences and some O'f tihese HlLaybe lll:il'f.'vel,sible. Thus, far these, the dear ]a:bemng:of 'GM food. mll]stbe II1~ade ma.n.da:t,oIY.

There is 11 cO]llpellm:g need to devel.op rn.rther ~lhe conmpts of b:iD]ogkal~egti.1lg. partknl!a:rly(mo po~entiia]I.ong-leI:TII ,effeds... SilJlce the GM po:t;ato !IoVO[-l W:iltth. male rats showed ab:lJlOml!aliilties in the d.eve]_(]IrmenJ~ o,~ theM' sex:ua] o:rg:ms, iitis ]:IDlTIperailEive tlh:1l~ &]]1Jm.l]arexpui!menilts shonld be done with :~emale rats to be foUowed by studies o.fthe effoJllis on

370

A. P,tJ\5zl.;;ii et a L

['ef"['od.l!]d~v,e perfuI1ITll"mce oJ rn.ls (or ,otiher .animals) reared end lITll..IJJiintai!IJted on GM vs, IJton-GM diets fo~: several gelJle:l'l3lt.ions.

H there isa genera~ w]l~mgID1ess~o .fu.nd ['e::;e,a.roh alllJ.Tlg these 01: similar lines and ,!:!he l!egu]a~C!n aeeept theQllJ.Tlcert of b:io]ogica.1! toxico.1ogical testing t:r.a.nsparent]y and j[[]t~.ll.sJjvely,~h,e me'~hoos aee available for the' WO,[l;. to sla.rt.fiO:Uaw]fiJ,g '~hils route, pu:blish.hlg 'lrhe resultsandconsulting the rubl!k: wii]~ ensure Ih.aJt a techFto:~.ogy whiGh pml!!l1l1sed safe a.nd p.1e:nJlEifu]f:o.od wii]~ deUved.l for usa]], and we are acmfk]enl that i.fpeor1e see rhaJI: eVeTytl:n.lng has ~een dioneio estaH:Ish.its !l.lJfety they'Ovi.U acaepl iit wjj]l.i.ngFy.

RelelJ'1en ces

A]liia]]lG! fm Elio-[lllt@g:r1ity WC!ibsi,tQ (1998) 1ii!f'I.-'l1W_bfa~lltegr.iJty.oT-gmdll!l.din,g CaJ;g~~R.AVIRSAV.Eil 1tOmaltoooporit,. pp_ 1I.--604![n~ab'ona] Resoon:h lmdDeve1.opIllQI1l,t COIJP_ ml ~~t NpOff,. W- 1'736-1'738; eoneluslons of the' IlXI?@:rtPll!lJiQ] ~llrd:m.s1illlQ saU!ty,oftlu!! R.AV.Eil SA V:ffi:1l1A to:ma1iO,1EN\I'IEilON, A!rIli]!.jj1iOn, Vir.~ gi.IlJiOi, pp.Z355--2382; four. we@l. oral {ili1lbuOOtl.on}liID:fciitj'sttruiy i.n rrllfus,t.y .rn::oc,. pp_ 2:&9S-3@OO.

Mttwoocl.. JDy D!adJi, J.N. 3i1ldfucfu:, R.L (']996) Stlib.iility 01 food. alIlfiseru 1iO digl!l'>tl.o:n .ih1 viw_ Nilrtru:fe Bir:.t/oc-hwJ{Jgy 14" 12.6'9--12'73.

&rlb~n.ch" S.A, bam,_, l-E.. J.a.cboll, 1'_.l.." Wood, .IL,.

StipaIllovi.c,.R" ]'laNey, .r" Patzer, ;5, and Fudhs, R.L (1996) Tht@ coIl1lUJffi:utron ofillsootpmlt@cwd ,OOtl!o.TtI",~0d is equiva]l!TIitliO that of COl1'V@11tlilllil.] .co.t~ .. lr:.tll.wal wf AgricuIM~.aJ .f;'ood! Chel'l'I.liit.ry ~ 36&-,1'7L

Bmns~m, KL"i3emst.@.m,. R~., M.i11QT, My 'Fi.=i.@'W,.

S"i3emst@im(. ][l'_n~ Ll!imnms, z.. ;S@]g:mdQ., MJIC, Di:D~@r;. D_[.. and S€lJigy, V_L (1999) Il!m[furrteJ u.~ in farm wor-kers aft@r '!TXiPool!im~o i:fa.cillw.; .11i1.lrillf\gj'~lSfs pQStiddQ& .Er:ii9irOlimenta~' Ht!;!!f.11i! Pe.rNptlc:~j''li'eS 107, 5'75-582.

~f'_s..,E[amTIumd. ltC and F'l!lcill'S" RL (200(1) Saft!ty andaJ.va111tages o:!fi!Jtr(;'i1hiS thMrj'~giru:rsjs]JmI:@crod p]anit';: to oo.nUQil pests. R:egu/i!'i!Vry Tuxf.cmogy a:nd I'Jm.rmaoo!o:&Y 32. '.~..56--173 ..

I!md:sl@v-R,QI1ISQIlI, C and POI.J!1s@Il, LK ('U99'7) Has<I.msofWlID1t@1lt1illlill!mtmltrona]:mbool!l.dii.,CffI of ,al!1@:rgemmto :foods_ AlIefg!\!, 52, 1]84!,-·H.8lii Brake;. l and V1!lIciu)s, U {(993)o lav.a]uattion of 1tI'1lnsg@Jll..cE'!I'1mt 176 'B'ti:' corn. :i!1l: Dl1oil!Q\r cnickmL .. ri!JI.rJlhy SCienCf' '77, .~6,53.

E.riJtiii;!h [:lbrnry f'il!Q ('199'7) r'ulblrcll!~QliBl102'l3l SUP 1'H3' Clruil1don HBarrnljDi:DOUJ'll@11i!s,. .No • lUl. A va:ii1ab,FQ at: WV!!'W":maff_Sp" _ Uk/pL1II1I.1:h! p'!;.'!.'! cli'>l1(lon/mdQX.ntl1l

El!1i:ks" A_W. 3[]!d FI!l.cbs" .LILL {l:99.5} .A5.'ll!SS.lUeillt of thQ .QIlIdO£jQ1llOllffi aUer1\~s.m g)yphosat@lio.1Ql',ant: and oommareial soyihQlln V',arL@ti.@ll_ §r:.tJH"NIll'~ f)f.A1I.e.rgy ,I'md CUl'iiffll !~m~!j:lwl~ '96, lOOS-']i()W_

OriI1ter, A., .ForbC!!s,]J'I·[ alldIB1;}ir, G_R (2!00Q) (DNA stll.lbil!itym p]an~ tlssu£.s:imiPl:lcalforu:~O'r ~Q~:mi>Sllhl(! 1tr,aTIlsfe:r .of.~ fu:m:t ~Bl1Qttiical!1y ][lodifiioo k!Od .. F.EB:S .Let!'ers 24008, 1-5.

Do:urumg:o, J.L (2(]OO)~jQal1t!h riSh of ~QJI~~al!1y ][tmHfiioo fuo(Is~ many op.mi.Wls, I:mt f:gw data, SCieNce 2.88, 1'748--1'7·4R

El!imtpC!!lln CommissiWl.DirodorntQ C (2!OOO) Orinrrn of th.e'Sc:i@11Eif:i!cCOll1lllli.iitttooWl.foodon'Jh@ EvllliI:rn.lfcm of 1'oxi'Gdlogka.]~:nfulmatlOIl. R.@~a·itOO.iO thE! Sa£@tty AssQSSm.@11tt 01 G@I1Q-Eical!1.y Moo.i!ti@d 1'oru:aliOOs:'_ CS/Nf/fOM'/8 .ADD :r. .REV.3 fi.t.1...:i[. RmDpQail1 Corn.nssimll, B~ls_

Ew@I1i, s, W"R a[]!ciiJ'ulSXl!ai, A_ (199911) E&clS 01 dtQ'i:S amttaillillg g;@11eticaUy liOOdifi.ed poIta,tOll!!S iIXpmssia1g G~lallt:&.nr£ lIioo/('s Jetti.n on mt sma!.] mttesfuJ.e, .Lrm,cet ~ 1353--'1354.

E'Mm, S,W_R aTIld.IPu!s:z1!ai, A -e~999ib) A u.thocs' ]iii!p]y_ .L1nctl'/ J54., 1727-:!I..'72R

fams, N.H <llldIEI,;Sa]ll!!d, A_K (199S) [l([tQstrudtmal cbom,gESm t!bQillellirn. of mfCl!! £00 on deltamdo~axin-tnaU!d potat.oes llindb~g@I1lj.c poItll~O@-s. Nduml Toxins 6:. 2n9-2n_

F.lacillowsly, G . and Aulir:idb, K {200iJ.} Num.IbiGruil aswssm.enit.of .fl!!OO:'>f:ro:m gen@ti.all!lyuloofiH0cl rn:gll:rus1rL Jr:.tJl.FlfaJ @fA.1'iJ'mal ami!.F'oo Srjer~CJ!'S 10, SmpiPl.em.@n~]~ 1IIH-!J.94.

Hanu:m:md, Ili.G_, Vicmi, Jl~, I::i,artn~l]_. G_E, Nay]or, M_ W" Kru;gihl; CJD_, Rohi]]lsoJl, EH"F'udhs, RL aTIJ.Plldg,l!!I:ttl!!, S,R.. (1996} The' f~dmg V'a~I1Q off soylbelillis,~oo. torllH;:~ cruck.eris, catfish aind dairy cattJjQ iis not ahemd. by geilJle1ti.c moorpomt'io.n. of8'~YiPhosaJte' to1leruce • .1{wmlll'J of NMtri~j'm1. 124 71'7--,'7.27.

Harriso:n,. LA.. s Hlai.Jej', M"R., Naylo:r;. M~W~, Ream" JE.." Hammond, B.G." Nlim, ItL, Bll!rn.@lti.@" RL, Nic~ TJE" .OOts.l}', 'I.A, 'Fayrar, M .• t,

fuchs, RL and ScK {].9%) ne

expoossed p:IDlt@m .- ihol'laW-ctol.~ri1illt soy-

bean; 5-ellollpyr1liVJ11shllkmn.a.1t@-3._(pihoophat@ syn.1t!h1l&!' JOOli[[ AgrliIDaci'e[;i!!N1 sr. Sltl;am crt, lis El3.]J!td~.y diSQStoo .~III m'tm and is no.t ~a>::i.c ·1tO aooJtQ1'y gll.V.a,gOO m;[c~ .. fr:.t.ru:rtiiiil{ Q!Nu.triUr:m l26, '721!-'74O.

HasfI:ilmo:to" W~, M.onIDla, .K,. Kal:Sulb~ 'I., Ohikawa,.

Y_,lmi:@E!; T _,. KitQ, :M" Utsumi, S" and MU!rllta,. K. (11. 999a) Safety <lssl!!S§illeilll of ~@I1Q-Eical!1y engI]]Jl!el1w. potatoes with de-sJ;g[loo. ooyooan

glycirun: compm~ttoilid aNialysBS of the'potato iDUoors and d1:&@stilhiiHty of I:he'n@wiy ,rofn'iE'SS~. ]J]iOil!!!1n iIlitrill1s,@g]JIi.cpoliatooS., f.(JuFm:rl ojScrel[C;f; {)OJ.f;ood tllid .IIgri£Mfhr.rt' '79, 16@17-16']2,

Ha;s.rumOitQ,. ·W"M:orrurt..1, K" YOOI\. H-J" Ozawa, '5", Ohka",·a,.. v. IsiI:lige:, r, K~IO, M" lJ~um:~ '5, and Mura1!a" K" (1999b) Sllf@fty as.sessm.cmt ol 1i[aI1isjjf!nic potatoes wi1ill1 soyooan g;llycim.n by f@oo.trt;s siDUdiesm rats, BWSC~'imC;f; jg~'~jffdJno'ogy !3liocJlemf.s'tI'Y 63, 11942,...1946,

H@linl, .RM_ andlll!:l~ AW., (2100I[I) M.edhl3.nfislns of fuod al!l@r'jjY_ Cr~r.rt'llt Opi'.I:IWN i·1iI.rJJm[l\l~wo[ll!' 12.- 647--ti53,

HWiJw~ U" and DO@riiler" W" {2(01) Ontbf!,fa.1t@ (]If p]ant and ot8h:!!I'fou.ug~ £looe'> upon 'the uptake in food or a&wlntrll:mucsrularmj0CtioIlW ][ti.c@" MoJI!1r:~~la.r a~m! General Ge.!1e/ii::s 265, 22:>'-233,

Kramer,B:.L Mor-:soo, r.n, Thro:mie_ J_IE..., DowelR, F_IE~, Baiilr!!Y, M_ ailldFH.<owa:md,JA. ~W\')O)TraillS£l~c a.vidm NIla:i!ze' ls ~UslailltlO Stor;1S~ :msect pests, NI'I"un .!3lroternIrJ:t/ogy: 18,. 67ia-m .. t.

Kll!iiP~, HA, N(]IteoofIl\, HP_JI)",L aIlldrl@.~II1I@Tll:nJ![& AACM_ U 999) Adequacy oIf metn(]ldslO:nesl:::mg'ii!heo safuty of £lgru!'lticaUy mooifi@d lioorlK ~iticet 354~l:n5-'.~316c

K1J!iiPu, A_R" Id.rl!ter, G,A., NotOOo[]]J,~:r.J,M_ and F;;ok, E.J (2001) Ass@ssm.ent (]Iftlhi@ Iood .s.afemy i.:SSl!iesmla~oo. ~o 8!ffi1ltica~]y moofif.i0cl. foods" .Pl~iti~ JO~j'rnll '9, 500-528.

Lapp~ M_A, ElaiiiLey, Ell" ChlMress, C and ~tdJjiLl(.

KiD.R (]999) AJ.t:@f'atio.1ls tn cllinl!C;}lliy mliPOr~ tant phyto-Oe'>1i:I'iogem in i\'eol!lI~cal!ly mooifi@c\, h~bfci,cle..ci:Ol@riilnt s:oybeaTIl'>.. 1(I.rJr~ra{ of MeaiCJlfI .Food 11, 2.41-1,1,5,

MerU!T, UK,.S!JoU;, KP" Bill!J.ro-Jo~ W.A., G1IDver, LA •. and fl:mv. HD- (1999)~leoo£ f!riar!! DNA and.~atimn. ,of ora] baC!.er1llinl Strepl;{IC(I'C('rJ's goJ'ilDllii D1.1 plesmid DNA in human :salli.va,. AJ.i'pimd a~[d END.irom.II.e~lltl'l MiCl''DtrJi9J''D,R\i!' 65, 6-'.~.!1

MelCallJi~ D_D" Asmooa, JD" ']'OWTIS@1ITiG, lil" Sam.pron, HA" Taylm, S,L and .Fuchs,.~;LL (']996)' ABse'>&NIleilllof the· aiL]~rcpott@:nlbla] (]If foods d.rl!rl.l;r@d~om g~tirnllly ,eonjjinerl!H!d crop plants, Cri1j'rnl 1ffrnisms iN .Food Sdel[c(! fIM Nr.ltritiD~ 36 (SUiPiP1EIll@1ITik), Sl65-Sil:B6.

M.i1Jstom~,IE"IlJJ:'W1.I!f!r, E" and Ma~;. S, {1m) Beyond substantial 'Bqfll!jV'a.]oon~,. M~f~jr:e 4!O'.D, 525-52.6,

M£!Inl[lla, E:, HashiIllotto,W" 02<1\"'3, $" Kln~'laj" :S" Katsuoo, 'r, Thkai~ F" Kj,tD,Il!.'L, iJJts1J!ml, S, and Murata.. K (]999}Qualii.ty and .s.af~ eV'ah!.I.at1on (]If i\'ffi'I@ttcaIJy '~.gfne=d :rliIJ~ w.ith ooyooan :slycirull:aI1ia~yses of th~ ~([I ro:mapil>:;.itiOil and digestiibi!lity of jj]1r~ rn.~i\'eoEllc rim_ .iB.WscJ'~lDf' Bii!l.tIl1clmQ1.oyy: .BiOcJl~I:!'Stry 63, 3'~4---3]~L

Nahnmra,. R aNld.Mll~uda, 1i', (1996) Ricea.l!Ir!!r-geruc protem . and mO]OC1!lbr~grnetic approach Jor I:Ij.pwlJl@];gmic ricel .1AAlill·tmt'e BioJ,OC-hNwOgy jgj'K-her/fiSilry 60, 1215-~~.21L

NOIlU~ J.A, Taylm" :Scl" '['m..mseond, JA. and Thom.as~ LA (1!996)~.ctBIlti.f.imti.ml. of .8. &razil :lIut aJ1ID:geIlmtrnnS&~iCoo}'bgan" .New ENgland' f~!jnlrill of Ml!1Itj,c.i~~ 334, 6:B8.-692"

N.OltroOrE1i" ELP.J.M" Bl.eTlf!mIlanJ'll,-rlolDl,i),.·'LE, van den Bri!r'l} Pii,ji" Ailmlk, ca .. 'l" Znlla, L, .lll:aynl3.em, A",f'eml1, M_ and K1J!iiPf!r~ RA (1995) Saffety .~sS][tEmt ol1ill:leo .Bt:rc.ilhls :~IJJ!I~riMgial':lS'i9ins@dti.cida.l.aystalpooteom. CPlYlA{b} rI!);.~ m InlllsgrlmJ.c lomalO~·_ :rIll!: Engei, KH" Thkoo'lGii, G.lilo and '['ernrusJl!i, .Ill:. (eds) IICS :SympDSjnm.~ Se.ies 605 Gmdj'Cfllly Madififd foods - :S.~fety Js~mfS_ Am~jCl1lIlCBI.n:tical. Soct~, Wasbin,sron, DC,piP- 1:3&-l4'7_

NO'''t .. k, WoK. and ]']:a:>J1berttef, AG. (2!J01D} :;ubstantial '~ival~a!! of an1il:rn.l!lt[i!ll!,ts 3lldiiIill.rl!reTl1t phimllOXiIl!;: :in 8;eneti.ca~.]y mooifioo novel food:;., f~ a~[dCJ1~i'l.iClli\fJ"oxjC'ii\logy38,4'73-483,

O'NrI!.ii1, C" .R.oos@, G" and Leihrri!:r" :S,R (']99&) Allargeruc potranti<lll ,of mcombmntffood pmt@l!n&, .Alk.r;[1J!'.rilNd CI.!~[jclill immuliotogy:Ii:l~en\\fiIti'mi'iilli(}, 5--9,.

o.msky,. M., ZhOlJ!l, G" Osuska, L, Ham:nck;, .R_E., Kay, ~IiI,.W_ alld M.tSf'a, S, (WOO) n:a~@DIc: p~;JnlS ID:pm;.g:mg rnl!:iontc IJeptid.@ cbimerll5> ~illbi1tl:lrollJ.~ECI:rumfC!!sistaI1ice· to pbytopllth{ll8~' NI'l~'un .Biotec.h1:1.o-[[i'g:y: :~8,. '.~J:62-'.1166.

hdg;el1te, SR, Thylm, N.Il" Nfda. DJ ..... [i:aiilr!!y,I'IILR, MacUoIlaM, ]" EaoiliWn, LR and Fucills, .RL (19'IJ6) fi@ cOl'llposi1tion of8')yphm:alt@-tolrlm1l11t 8oyb~Ilt sseds is '!XJU!i.'i'a]~.t to tI1~.t .0£ OOTIveIlt!:01l131 soybeans, 'tm~m.-:il oj NrJ'tr#i·l.Vll '].26, 7102--,'7M,

Ii'Uszl.d, A {2001} GrI!.TI.eti.caI.]y mooi£i.€!d. ~0tIl0ds: an!' 1i!h~ a risk to bumanlaTItiim131 heatl:lht? Ava:liI<l1blf!' ,at V!l'I.';I'W·"llctfoIlibIosc~enm_mg! brotJrl/pusztiili.JII,tmi

FUsztal, At.~ S,W'_B" Gralll, G" hU'J:llana., W"ff." van .[)antm@,. EJM"R1!1Ihio, Land l3ar-doc!;. S, (1990) 1il~EIl,HoMffiilip betwOOIli. s.llI.mva~. and brums: ofphmllriKMIs dur:mg small lIllt:l!rS,lbl:rnal pasSi1®~ and 1ill1~reffec1ii'!lrl!TleSs as ~lh facrors, DjgesfiO'.N',. 46 ~SIl'PP~eooeIll 2), 308--3hi.

Ii'Usztiili,. A" Grant, G_,. OI!:l;guid, '['_, BrowE1I, DS., P'rI!l!imlillS;. \1iI.1-- Van Damm~, E,J_M" and 1lJ300.0cz, S, (199:5) liIlh:ib:~I:fOil (]Iff;taochdi~eost:ioo by O:"!l.NIl1ilas@mmlhi~or rMUC!1!Sthif!' mlld.mcy of utilliza1tl:onofdir!!1Il.rypl'OiI!edJ1S ;2[t,j lIpIds and [i81a:rds.1ill1r!! g~QWI:b of ri'l.ts_ fOJlrt[ilI.l.of.N~t{~tw~1 125, "]£54!-']562.

li'Usztai, A~ Grallt,.G_, ·l3aro.ocr;. 5" .AlonSO;. R, ctlil~I!sp@@ls, M~J, SchmOOeI, H.E, 1i'a:h~, LM. and HJ;Kgiins, 1i'.J V. 0'9991) Expr1lssi.mJi off

172

tb.{!insoct!icidal ibea[l alpha-amylasa iJnl!Tiilbit.m 1tr;a11&.@~TI~ has [lliiniMa] d~lmjffi1tal. dled! on the' I'liutrlitrom.] vanu~ of peas fad to rats at 30%. of 1ill:J:~ diet~ jOMrNal of J\l'MifriUolti 129, 1&97-1601.

Rea@]'jioo.ugh" .K,&'H:a1tl\. 'iN., MarlliiI1l.Ba1!i, R, KmmlN, M~, :SheM.y,ffi':" Smtd@fs,R"El,oocik, C. and Em]ay,lD" (l992} S{Jjf.ty A:iIH'8~lfmM/G.m13tJ\cany EngiNt\f'1!f'd f.'[!~lrs and Vc:getrrbI6: a Case :Sl'udy fJj ;tljf FL4 V.iR. SA V.RTIii ToDnI'£iW" eRIC P':Iiess 1:E1tCv Boca .Raton,.flortda.

Rog:an, cr, Elookmlt,. §.. T,lDmtcan,. D_R.,Pl:Jeihs, RL.

Lavriik,,[,' .a, 'LQVI~ :S,L, .Mu~, M.,. Olison,. T., Owem, E,D.,. .Ra.ymilllLd, IP'J" and Zamw:'ill. J (WOO} O:mlpoli!i,ti,{ffi~l anllliys.Js of tubers from ~rured! and v:lin!.!s :li2SiS1ta'm potatto plantt& fOMrNal {}j AgrIcultMlfal aEd F~ CJt£mi'l;~ry 4:B:. 5936-5945,

Royal Socr~ (1999} Rt'Li'i~ of £111m OIl Possr:trJe TalJicHgD/GM.PoDtfIti:iIfS" .5lJoya] Society London.

Rl!lIbio, LA~, Grant.. G., Cabal!l~ C, Manm@ZAmg;om, A andlP'u:sxt!ai, A «]994l} H~8~ iifJ' vivo {roO wS,e;1riiIbiillHy of faba lb~lj]l (Vi·Ccil'lfo'b.i:i),luiPln {i!~pia'lill!~ .rmg~~sl:ijiJHus) and soya. fuelm. (GlyciNe rJft:rx) sol.l11Ihl.e' glofuuil:i!ru>. joD!i1'im1 of .Food Srit'!u ll1~d Agrk'1l.1M!lf1f' 66, 289-292"

Rlliba~M~dieta, N.L 3ndUnIS,:EA (199S) Nov~] aNid transggkfood {T~: ov.~r:i'~ ,of scuen.t:i~ VEI5l!lS p1!iIhlk p~IDC~. na119gfltiJr: .1'1e.5fiird 7,3'l9-3S6"

Sdt1!1lbfu@rt,.R., LettmanIll, C and lDOOr:lil!@T, 1i"'i" C]994} ]:n.gestoofoooigrn (phag(!! M13) DNA S!lI.TIr:ives ltrn.1l£toonly m.th!· &a s tr-oim~tIDsl tiro1lct and enters t!l:t~ blood s1bD@am of m:to~" Molt:edrr ~~r:ii' Gt'I1t'm1' Genftf.cs 242" 495-504L

Sdt1!1lbb@rt,. R" Hoblw~ U" Rc!!ru!;. D. aruclDo~f.Il~, W. (]998) On th~fat~ olor,al!lymg~ted fOliE'i~l DNAm ID:iCl'!: rnIOIuo:w:ma] aSBocia1tijcm and pEam:n,ta.] trnllSM!issioniin 1iI:t~ :iferus., MoJ~;::ilIla.r ll1~d Gr::ltf:.n:ll GItNei!ic:!l 2Ei'9, 569-b."'76,

'SidihllJ, R:S" Hammood, i),G., hems., RL, Mult2,.lN" HoM~ LR,. Goorge.. B~aI1Id. Olsoo, ,]L (20) GllypihOli!a~~O'l.emillt rom: m.e oomposl.1iion and

lfeOOlng va]u~ of ~am foom glyphosaite to1@l'ant com til, equ:~val.ent tOo that of oonvg.t!kmai rom (Zc:r.i maYs L)" J@!~.r~UlI oj Ag.rtcIlI1/!!.Ml {JEd Food CI!emtsuy48, 23@5-2312,

'Ia.y]or, N.R, FuChs, RL" Mac[)o]1Ia·1d,. J, S,harillf, All and rllJ.S~1tit@,. BellI. (1999) OJlI'l1potli1biJDllilE aTIiilysis of S-~l1PihOli!a~tol(!!ro1l[lt soyfu0am;: tr-eated. wi,th B')yphoSII1t@" !@!u1i1rll &j Agnct!l.tulff a~a!' J!;ood Chemistry 4.7,4469--44'73"

'Ies.hfima, R, Aldyama, H" O:~lJ[IllJki,.:HI" Salushu:l1lli" J.,. Goda, 'Y~, OI'lioo.em, H, Sawada, J and ToyOOi.i,M" (2!00D) EH0ct o:if GM. and ]1jOJITj,JGM soybeal'lis,Qn1±I!.e l.mm.uru!.systilln o:ifBN Eat;, aTIJ. BIOA m.to~. jcmrl1.QI' of fh .Food.HygJ't'l1£ Soclf.ty &f JI"lP~~i 4l~1I, 188-193.

V~ Padmn, R]" MmiI?I1Io EE!ITOs, L. N(!!ri (l.;azan,. L, ID@ ]a .ru.va, GoA and Lop!?:!: EilQVj]]a.. R (999)1Ni1:fil~13s.1j['ic aad :intrnp!N:'i,taTl~l adm.trLi!sI::m:tion of Cry]Ac pro1ioXID from .!J:adWlss t~Jlm)ii'gj:f'.N'sis i.I1idu~s Syllt.~CC and mucosal antl1booyrespons~ iIll m:tcj~. ufo Sci:e.N'Cfs. 64, 189'7-'.~.912.

VIl2CJ!IffiZ PadlDll,. RE., M:ooon~A.ef!:os, L,

NE!]'j-~I'li, L, Mal'1iine:z-GiI, AE, de ~.a Riv,1li" G.lL and Lo[p{!ZReviilJa,. .LIL (2!OOOa) Cl:tamc~@l'iiz:a,timTI. ofth@ mucosal aad syt2m:leimm1!l.TI{! JIi?SpmliS(!! induead by CrylA.ciPm~~n.f:ro:mr.t ~'lh!s .~JJ;ur~·l1gi~:wsJ's HD'73 .in [llim'" Brn.tiIIrm fOJlrNIlI.1 oj Mtilka.1 ~ltid Bfol{}gimf iRc'seJlrrch 33, 14'7":155"

VIl~~P'admrt,. RJ., Gom;a1~ Caibrera, J" Garcia Tovar, C.,. NeriB:azan., L,Lo[p!?:!: .~e-v.ma, R" H~ud.0z, M" Momrm .f'ierr:oo,.L ailldDe' la Riva" CiA {200llb) OylAciIHo~cocmf:ro:mr.t !lat'j'/h~ tJit.Mrjirlgif'!lsrs siP. kll.rs~aki HD'73 bmdsltO So1ll'fam pIDtce<n :1iIl 'Ih~ mousa smal] rn~!?S'liiine" ~i®c.F!etlJj,rnl ~~d Bfoplly8fMI'Jli:i!";liel'j:l1r!~ G:m:!II:l.!!~~ij;rn:fiO'lls 271, 54-58.

llS food and Drug .Admirustratim1 (1994) M@morud.llillt dated. 1'7 May" Summary of oo:ru;;1!rltil,tiOI1l Wl.th Cd~'lmiC., a:mcemll1lg flLAV'.ffi':. SAVPto:matQ@S. Avaiilab~~ at 'lo,'WW.brCi"int~rlty ,or-;g

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