Document qXRG7808KMvVp9eyRLD6Vk7G

EI18636: Slide Revofpianecrewas lesionsfrom DuPoAnPFtO Study DateofReview: 28*Noveraber 2001-11-29 ReviewingPathologists: Dr E E McCoanndDnrJeR Flostler Stady No: HN-18636 StWuydlydT6i63f.le:CombinedChronic Toxicity/Oncogenicity StodywithLinuron, C8 end `Concolftuhesreivioewn: t`hTheerovfienrdailnlgcs.onTclhuesiroenvoifetwchoenrfeivrimeewdotfhtehceatrcwionsotguedniiecsewfafsectthoafttAhPeFyOwienretnheotDiunPcoonnstissttuednyt.in ``vaandstchoensmidsetreldi1l0byeexapldaencarteiaosnefdsrentshietJiavciktyfofoantohnedceovgeenlcotpimceenftfeocftpaonfcArPeaFtiOcianctihnear3eMffsetcutsd,y `sctoumdbyisnheodwwietdhthaenfuunlldseprecretprourmtionfg oAfPtFhOe-aicnidnuacrheydpeacripnlaarspiraoltihfaetrwaatisopnrsfesoemnth.yTpherepDluasPioant 2ts ahrefrletcootciaonruocifgnionmhaad.eqIutaschyoiunltdbheenoroitgeidntahlaitnttehreprceotamtmieonnotfotnhuensdteurdryebpuotrmteirnegilynroeftleicnttsetahdeed . fyaecartstshiatnkcneotwhlee3dMges,taunddydwisacsrriempionratteido.n oAfftihneaslecsuobflnepfancireorafttimhcialsecsotinoncisl,ubosaisnoandvaanwcaedaiimnttohrsee extensivereviewofthepancreasslidesfromthe 3Mstudytobecarried outbyDrMcConnell. +SLuAmllomofftthhaeerneerovpileyaws:ticindingsoriginallydiagnosedon theDuPontstudywere 2. E`lceonvfeinromfedt.hehyperplasia originally diagnosedingroupITontheDuPontstudywere 3. Tdwooo fthewhyspeorn paslasniog atstoorbir egirneapla olrytdeidadagsnhoyspe eerdpilnad gsriao.up ontheDuPontstudy were. 4. Adnaddo itiow nal5t0wn ao3acniog ntatrobhr yeperreppla oarstieadsdawsehrypeeedripalgadnsoias.esingroupIT dingthereview 5. 1praoscpeisteswofhithcehswecehraenngoetsotrheigovlelryadlilcsognncolsuesdiaosnfsourcthh.eDuPontstudyremainedthat 6.AFoPllOowiiantgiaslsitmuitdeydhcaodmsbhionwendrea vciaerwcibnyogDerniscFeofsfteecrtfaonrdtFhreammael,eorfatthpeapnacnrcereesa.sslides f`wreormecaopnpfroixrimmeadtienltyh3e03aMnsimtauldsya(snedlaeclttehdbouygDhralFroafmteh)e,anseivmearlaslawceirneanrohtyrpeervpileaswieadsthe ipnrdeulcimeidnianrcyrceoansceliunsaicoinnoafrthhyepleirmpliatseidarseovinetwhwea3sMtshttutdyh.eDedriMd aoppCeaor tmo bhmaeesabnleeAlnPFO- requestedtoreviewall ofthepancreas' rom the 3Mstudy. So Introduction: ``TohnAepPaFthOolwoagsyirneivtiiaetweodbfetchaeupsaenicnretahse'3Mromsttuhdeyt,wwhoiocnhcwoagsecnaircriiyesdtuoduitefsircsot,ntdhuecctoedmipnotuhnerdat t``hwwaaessmnraeolqtuecerastrt,ceisdnthooogcewonenidfcitarocmlteohaerprroaennfccuortgeeetanhsiewchfeiiflnfdeeiicntgostinhtnehDteuhpePaponancnrtcseratetaaisdc"a,cwrihonimacrthcheewltlasws.ooTnshlteuyscdioiendsdeurcetveideiwn STiheeorfevRieevwiteowo:k place at DuPont Haskell Laboratories, NewAsk, Delaware on 26% November 2001. ThosePresent: . DDrrRJaonhdnyHFaranmes---HeSetaunddyofPaPtahtohloolgoigsty,, DDuuPPoonntt HHaasskkeellll LLaabboorraattoorriieess,, DDeellaawwaarree,, UUSSAA. DDrrGCRKElceomb~n e,HeBin aodcohefemTiocxaidlcoTloyogyx, DiuPeonoDtulHnadsoekeeglUlniiLvasebrosrtaitt,oyr,ieUsK,.Delaware, USA. DDrrJJoohhmn BRuFtoesntheorf,f,ReTvoxiiecwoilnoggPiastt,ho3lMog,isMti,mAnsztsrotaaZ,enUeScAaPharmaceuticals, Cheshire, UK . DrE E McConnellReviewing Pathologist, PathLabs, NorthCarolina,USA CondofuRevcietw: 1. TPhanecSreTaPsGu(1i9d9e5l)iwnaessftohretbhaesidsifaogratoshisdiofaPgrnoolisfiecrcartiitveerLieasuisoendsionftthheerEexvioecwrpirnoecess. 2. Tpoagncertehaesr"wfirtohmDarppFrroaximmea,toenlya t3w0oahneiamdaelsdfmriocmrotshceop3eM,DArPFFoOsstetrurdeyvwiheiwecdhtihnecluded 3. DwroMacnCiomnanleslfrlwomastnhoectoanblteotlogrreovuipeawntdheth3erMesmtauidnydoenrftriosmotchceastioopndboustehgarsobupe.en g(irvepeonrtthpeesnldiidnegs).romalloftheanimalsonthsstudytoreviewinthenearfiture. 4. EFEoMrGthCe r)ewveireewogifvtehnesDuumPmoenrtyAtaPbFleOsSotfutdhytohrirgienvaiedwiianggnpoastehsa.logisis (JRF an1d 5. D`wrheMrceCtohnenpreelsleinnciieaolflycrietvhieerawceidntahrehpyapnecrrpelasassil,ieddesefnroommaoonrlcyatrhcoisneogmraohuapdbIeaennimals areconrdeid.rmIonmaagdrdoilutpiosInIh.eParnecvrieeawsesdltihdeepsafnrcormetahsesgirdoeuspfo|comnatlrloloafntihempalasifrreodmctohnetrol 6. DDurPFoonsttesrttuhdeynwienrdeenpoentdreeavtileywreedv.iewedthesameanimals 2sDr McConnellfromgroup IMNcbCuon,nienltlhbeaindtceornessitdseorfetdismheo,owneldyprreolviifeewraetditvheolseseiaonnismaanlsdforrotmhogsreoduepem1tehdabtDyrthe 7. sTthueddyipaagtahoosliosgfisrtomtobhoatvheDsrhsoMwcnCloensaioenlsluanmdFtohestoerrgwienraelirnedpeopretnodfetnhtelsytruedcyo.rdedand - 8."tAhueyndwiesraegcroeemmpeanrtesdb.etweenthereviewingpathologists weretheareviewedtogether ``oandd&ittwoon-alheraedvieedwmiocfrtohsecsolpideeasn, dto&gectohnersewnistuhsaregfreereednicenctoontshiedeorriagtiinoanlodfibagontohsitsh.e i 9. rDedrevbsireiMewefe.CnodmweelrelFjoositnere,dlHtaenrsbeynaDnrdsFErlacmoemtbhe,eBnumteetnthoofdfiascnudssKtehneaefidnydifnogrsaoffinhael 10.ci1rwceulsaatgeriete1d tthhaetsDternFdriangmemweomubledrdsaffortcaosminmgelneptaagfeerrwehpoircthoftthherpervoiceeweidnigngs tnd prateholpogristes,s0oedfDnthrtsFparroactemeiediaonngdsnH.ansenwould sig thefinal versionasansccurate Ls Table 1 Summaryof JRF's reviewoftheDuPont pancreassds C|m T E EEMcCIRF| Consensus| Aged _Dissgres | An No Review Diagnosis singout of hyperplasia) Original Diagnosis C Tresor T hap eel] X `Hyperplasia-borderline `Adenoma adenoma (multiple) EE E:77 7 Y Y :r r =r yperplasia);| hyperplasia | Hyperplasia (4) CTE taemortage ie me sie) | 3am TT Rew "Adeooma HytpperpmalasGi)a = [ees] Mo Idic nen reviewed 0 [ET pr [S reviewed ag meme e [os re] . tt. 1 EiVonot| RASHE0R CC] ErrEeevvMiiceeawwoeeddt | RAGHSIT focus Hyperion TAD Hyperplasia (2) Fm 7 R494552 Besophilic focus. `Hyperplasia (1) + basophilic C TV TTweReI n | | y Fospearppisn |Hypfeopculs a(|] [ TrT ews | wapy 1 [| Adem|X] R494633-2 `BaHsyoppehripllicasfioac?us; `Adenoma. [ TreT w@s| wapV Cr 7py `Table 2: Comparisonofincidencesofproliferative lesions in the acinar pancreas between [Acoarbyperplasia | 8 | 3g [[AAddnwerreawdecnhoommss--T 0 y 6 [PL oa | 7 ----1 [7p3 7 ] [[AAcchhaarrhsydpeenropmassi[ a |6& 1 71 [PA oul 5-- 3-- (EoaElmmorsty | mT % | IR Foster 1% December 2001 5