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m m -va/ Study Tide FC-143: TwoYear OralToxicity-OncoqenicityStudyinRats Peer Review of Ovaries Authors Peter C. Mann, D.V.M. Experimental Pathology Laboratories, Inc. (EPL) HPOernBdooxn4, 7V4A 20172-0474 EHES.tlaekIsv.tkoedennullRRPLo.oaFanbdrtoa,drmPae.teNoO,reDy.mB.fVooor.uxMHr5s.e0,aaPnldhthDCao.nmd Epannvyironmental Science Newark, DE 19714-0050 Test Guideline: Not Applicable Date Computed: June 25,2004 LaboratoryPrefectID: DuPont-15261 Work requestNumber: 14459 Sendee CodeNumber: 1243 S ubm itted B y: NEHE.leakLwstkodaenrulklRP,LoDoaanbEdto,drP1ae9.tNo7Or1ey.4mBf-o0oo0rux5Hr5s0e0aanltdhCaonmd Epannvyironmental Science A u th ors \tki\ C . V(VNV- PVeetteerriCn.aMryaPmat,hDol.oVg.iMst., Diplomate A.V.C.P. D ate________^ J f t / t s l ^ 0 0 ^ ______________ DnPont-15261 PSrtrein^vcebinptaRJl.LRFeMrasemaerc,hDP.Vat.hMo.l,o2Pgih^sDta.n,sdDsRipAelosem_aractehAM.Van.Cag.Per., Pathology _D_a_te^ ' \ d ttf l Q - 2 DuPont-15261 FC-143: Two YearPOerearlRTeovxieidwtyo-fOOnvcaorglee*nicity Study in Rata TRDPoptLigonrrrhhaaiioaptd.ebgthDdlslioiisaiefnw,nrlegmiaaDfgrdenoltaa,oleriolytpetalrsiesoivslpete,fwiexrwesAcmo,aelinenemmmIralnosgtrleieimcetonrahr,.veins,eeAecipds3neiaonmoMwncoavtrlneefCaetar(rdttdrpPhiouicrebrlerrealeeosyenpotjgaafoevtrCntewcoraidototormoeynNlcdflv.eFrVoubegiTCtmfyteeeedh-troDreb1eiiiaer4nefrpiVrn3ap.aenRr:ae0eeyrdTe2ortyerp8wrbrrPreae1eieotvanaCrhvdtitYaoeRhiGriewloeye0woedla0Pgopirl1fiagaaOis(2gntittshsh)srrdtt.e:oaousielPnlldToaomTgeynhggstoedeipei.sxnsraptStiTtstsCcehto.hiede.oTtnviyriMslshelo-rceOaeengausgvnsiRnisrsiolnsceeti.n)de,oewFdDefmgdrosefiiaVerasonwmnsgRcMiuctenueieiir,o,sktsesyeDserderreS.esVfoltlauane.Mtndcedytde.,idn Materials and Methods rpAdAftnpewheovaioevpaleoetaelnhgepislrsdeekunoeelrwaisaonoleadtotd.vosafniegeoTiitniasxehismnshrwsleA,aetieta,ssnauslef.etonsddoeevIvadtpdynetahnahatpliatraihunerhmiestaeeacopetdsastalesierueivlofdeeserdransedorciehiavsnlrmadaaam,eitsedfobtvtehteawhleisateeeoohrfnwywdbesvoSyweiywhas3adperesgteiwiarahreanaornecesgeneolirfienmiwssinofmfkitoeoiesuaescrsatldrpaieeoslesityssdenniwnlvatcfpiahsosoee:lattuatrrtrutelfeetdhaetoddvhdesvoneyiidieaaloeoe.iosinwoitdTnlgna"ptvsheiobApsrtariehneltanrigemiwseatoerhtofnehrsreooreseierbmtfrlap"eooeapco.oagmfrtrvFeroliitesteafsoahriaitrnrtedcrecihargeeefSheatgosio3vaatmraeinveirdnnwepedeaaiiwedumeeinoledeir.aawtaapfkhbTlorltyosilelhnhtaeyssohreerieofstdnesfihooroenogoserrbaeitiifttfetugivihdhsnfaadieteosaninulynt.traipada,eaSilleynalyi5ennso3rdcirse, below. Criteria for Diagnosis of Proliferative Changes in the Ovary mTcwasIanhadphhaosdpticiehusiecrstelahiog,dornvotinhtnsoneo,eosranlsmitfduoceobatutarecelpmllaeasdarltrlegrligcvasosileeganammlncnnglsuaatodolyiomssnvce,lbahaabdiernyraucyactntaeosygotprmpthesofprteerppieoyatlramilateiahrsfsslo,ieamengrsvrneael.efattnoTcsinaeveohadselcoseuschcv,emsaahaanmbranlrtaotinaahcacvlgroontleeearugsrspcngilt.hsoardhotnarihamcnfdoagslfaev,ei.netlsleTiaenaaathegtrsdeeedreresarnbevnctooyeeu(rlllllmiucolafsutproaem,brliafmonofla)itoyadoacrmahpeialnapylgclvtesieeanearmlprglsaapsta.rnietyaIacintareasal.,lsnsgIoaocnlnmaedneds. Pocc(Dalbratosiesxelsgirofiovfenirereyaeddttiiinavancsle,tlehul1eiedt9sheo9ioes9vrnl;aeesrPspi(ieeohilstuynhfspseroleociramoaplnm,ltdaghpsoGeioanscoaeourdddrraronolenefnso,tgtrp1rsola9tmaun9sdu2aiay;llo)A(wssinaelei,txsrrtoeihcnneaosclreildactgl-at,sooltln.ru,toaht1emde9aaa9olll0ovs))taror.rsoPryemgrraotearolrelimlfiige-nlreciaonketreeliilvrgcaieinelnlllye.olssr,Tiiogohnirinss 3 DuPont-15261 mhrTiashiskxu,besdt,euefpmonororpterhucsilosdamtepiroeminveesrendroedffvertidohemetwhse,aghtocyfneoplalredtfrayoplpelaseptssruioa(rDmpaoniaxsldoecnnseeoleolstfpsablinae,sa1cilaoy9msw9i9seb;raiPennedddduieas(vgPoandloauunsasedtodiGoaanonsrodgdfoGocnnaoa,rrdc1dia9onl9nos2,gtr)1eo.9nmI9itc2a)l. Gonadal stromal hyperplasia is present when the interstitial and/or sertoliform cells (but ntH(uionybtcputrehleareaprsnplianorsogrimafgilwarealsadlsuoetgfewrsaatilrtdohcemedinllafcsrl)rocefmeaolsrlim1sn-wg4d,siitdishzceerop)eer.tnewdoiitrnhdgoiuofftnuatsnheeianrrceerlaeasatiscveoeninstiafziinebiornofgutehsneclopanrrgoneleidcfetcirvlauetsitotiesnrssuoe.r bThpdsdcfooooyriiyaaimrrtpmpggrhteeihenncarsaweooparpdsyssllhoeelaeiyascnnsdl,t,rieodaitatismsthhferifteoebfrraoooirnicoateemasrrnnabiaditdrndrgoeiyeachroiufimflnnytafueeoaapedaerdettseseceuaritdnlrpnalertebolagasiaatlnrlforsietsotciifehnahfymtveigwepteaoadrllhloelleduofy-ssaaodugipedtorisjineemconigrtnnan,psoeolgolninbmafsnfaseasoligadaisoyea.etranuefdlflToaraOrseooltehtexsrmsneaoritmrzdthmtehtheeuaif.eacanomtlrnortdGooeaom3is,dtosracmt,atenooiltnnawmhipoandgeealmacu(lsaDooliidassrsbwisheetijxrescengofosocbcoomsntrearmindvesaosaeeeelotddf.dnaamap.tdlplIr,eoeSofrs1nifctalim9rinoionofn9cmenamca9ersrinaa)iiasd.lsstiilyimetzvaTenoerenahcenliceishsytdhtahiaedneta ModHchifaoaatgwnhnnyigesoveossseeftrwudt,hdtedoeyrueocervnoidnasniagurtgiaraeiensnrotoehdsduieaatdvtignnedneoruoyerssisveunmdabgltawultlehalittedaihoorreengsaveo(si-nDeeoawfidffx.eapoclrntoswetlritofaeamsrl,oaatv1lioe9hrn9yl9opw;oePhkrpieeclldhau,sswaioaloladupnuloddrsinGpsigrbootlrbhedaeopbnprlo,eyl1einf9reo9rrte2abv)t.eiivewe hInycpiedrepnlcaesisao/afdpernoolimfearactoivmeblienseiodn) sw(egroeneavdaallusattreodmbayl thhyepCeropclahsraian,-aAdremnoitmagae, torrend test and foe F iber's exact test Statistical significance wasjudged at P ^ 0.05. Results frIiT(oeTAononeaxffahpfsecafdalbepioemaidlelnepeclpeaeinttrrpnotnee1eadheerrcd.stisaiidsexemgiRrisnnospinAncaonsemtaeet.ahrfsslaTceoogttcssruhhvrfatfihdoufeeaecaiuygdrecrloiilipnrtyeabfroptc,iinerahcugrwieylodealpispenodleetoiostannrtfhiaherlreodcateterrenntf(etathhnSlosoopteieeutibcovfcbmccaogorteisoutsnonn)blenraaeneearedsnks--eanriyiyiidddoomd,oeeeannb1favaralse9rtaeralshfs8ndi(itronn5eri7ifoe"mrt3o)oteeasmh-rrratwtseiiwlahgrmlseiiloei/shgenghvksiihkraycnaa/ot')lhprctlueifymireennoprirsafiotir,pmiecmoctalrrouaesiofosvmms,isnagianacacgiordssovryaragiiwpenvfdcwrniidiorececdia/ivuelfeouslsi.epvcraaTalseTaolsavablrpdihruabasaameeialtsltnsestasenehiobiod1nutosmhln,tmweo.paiacsnrftbnTaeoildetnnsihehrrinesietrbeosnhsedTenftveitepeshuafiodexornamivwtuniiomanbn.r5rediat0reolss 4 DuPont-15261 Incidence of GonadalStromaTlHabypleetrplaala and Adenoma in Rate* Dose NHAAHoyddy.peepEnneeororxppmmallmaaaassiiainaane(ddT/oorta----lGGGNGrriroaaaa.ddd)deeee 2431 405 628040 12 43173501706 16 aAnim ils on study beyond the interim (53-week) sacrifice 34060 15 62531 17 Tgmoregscceivorrrrhgsooioinhtepnduruetyreeierprpefpocin(i.sawectltc,ishxaFveer.eanpeseorottstlleraaypifsbsean)ie,inx.ltoacigca3s/tHsairrmh0vatedeoa0edapedtwlseinlpyseefoep3.to,divmmci,rTenl4aeaarch(,ls,dPclieoitydeoor=irneemsnnnoaaic0ggtcdbmim.nerdei0naasniee4fdeondoni6dcemcitfad-aiefprnnaonsenr)tdroltooaiwrpln0etftirefacao.lo0eedsrtclere4sci4paidaf8uot/resi4ogrntrev,oa5grsseaotr,rioi6sleuvnteshf/piem4nshgesil7cyrooecCaipnmnadodoesnemoeocrdndpnhf3picslpa1raaeaagwr1rssnnoen/ioa4addloAis6ff(staerootaeibomrndbdocatesaitwotvtenhilanevroniegvtetwmurhee0olmdeeaaa,l3rssnbwieg.i0ndoerSse,rantFtor)haadse,imnteseatihhdosde3oitegei03tfrchnh00'3aseoe0lpomstsppetrisamzpintsem,, Discussion and Conclusions TrpeahvweieswwliweddeieswwoipfthoatvehmanrlipnehgsaioasitfsaroantnnsgpfnrroonamliHfeaarlatwatitvmoe-rylneersaiirhofynepseedorifpntlghaesstiouavdratyrrwygn.intLhareFfsaCilo-gn1f4sm3dtirwamgelnraoeHspeaendenbrmyathe ppnsdccduhooaaiearttarsmgfhhrinaegnooegcsnolnlepeooascsoggteelinaoidiposstdbinuttbtessh(ryoedeowerf,tnltvheiotgeueureodmetbghnsubriteaanruladaandsdtatruheihylahldeeogspyrtopsnarpatrnotohhoomcsamolpeeinlafsllooaellforgrsrtleauoeiifastsrmmtitueivo)ocb.oeorneurvTalsn-ledaaatbhslreretiyeinoyhatdpotnpnyeiumsepasr.bgetorarlernFoifwpsfoumglhlesoaroettacsuihndlctileaeadcntdrdoeeomsalrr(umllmhostgsue.ertsgebnrseuo,ucpsbmslletaeaacatadsrutnlerabrutddeouym,emrointanghoonoiercdnfm-upm^tfarwherroobeeearmrynspmrthateoohdlovsrvielioaeoeasggwrgtinuieacodnnsyetricic Etoxtcheopstefoorfdthifefeorreignicneaslisntuddiaygfnoorstthicen3o0m0 penpcmlagturoreu,pr.esMulotsreodftihspeapraetae rreesvuieltws owcceurerrseidmfiolarr the control and 30 ppm groups where more hyperplastic lesions (irrespective ofthe 5 DuPont-15261 nhociganoodyrfconmeptruhnteorepeoaopnsmpsll.cseaela.saeisnitSrauoros,rceiemaczvduueieeesrowerneevfdo,dsi)mtdtihwrenaoen,emrgocrereeraewloaoaldebtfeeresisernneioironcnvnrmoceesiadsa,dstwebaaentnydaicsdstletheoihscsebyiaionspplelneetyrhrevgpsreerilragadcedsnoviieninaif,etitcwrcwhooaehlmnpig3tacbr0ithnoih0nwcuoeprpldoeoptuagimhsnliadestgntscrsrei.oionnaBrutrgeepeaoids.stnpehgHdaoerdnroooadwuonlpftedsostvthirreeaoeernrml,tearsateiulavltetesdto References RASLalit,s.EoAnlwcRaedHlle,mMMiRco,PrMgraeonssnK,tgSToa,mnanDedriyeMgJroo.,nCptgpAo4,m2a9ne-dr4y4MJ2ra,cCkAen(z1ie99W0)F.,O(evdasr)yP. IanthBooloogrmy oanftGheAF, Eisuhsetris DPInri:oxGloifnueiDrdae,tisLvfeeoilnreiTsnioogxncirscJooRlfo,tghViecaOlPeavritaohroyMl,oUGgy,teJ.roSuhTsn,PsV/oAangRAiPnNa/A,,CSFIetaPrbv, WiinxsaaldsnhdLinOGgvtaoindndu, cDFtrCiint.hRCaHts.(U19R9G9)-.5. Peluso JJ and Gordon LR (1992). Normeoplastic and Neoplastic Changes in the Ovary. IInLcSMI PorhersUs,,WDausnhginwgotortnh,DDLC,,apnpd3C5a1p-3en64C.C (eds) Pathobiology o fthe Aging Rat, Voi 1. FISnhicbi.oi/n3rsoMkcih,CeUmomi(c1pa9aln8Fy7C.).-1T4w3 oinYReaatrs.ORriakla(*DEiextp)eTroimxiecnittyN/oO.n0c2o8g1eCnRic0it0y1s2tu, Rdyikoefr Laboratories, 6 DoPoat-15261 A ppendix A : In d iv id u i A lim i B i*r R eview R em its 7 W KS ANIMAL# ON TEST IR4676 26 IR 4 8 0 7 M 5Pm | 4676 4686 4688 4688 IR-4BM IR-4001 4606 4610 4828 HM 8 4631 4832 1^ 0 40 62 63 83 63 63 53 63 63 63 63 S3 53 83 63 S3 0 ppm (Group 1) ORIGINAL DX WITHIN NORMALUMTTS MALIGNANTLYMPHOMA, LYMPHOCYTIC WITHIN NORMALUMITS WITHIN NORMALLIMITS WITHM NORMALLIMITS WITHIN NORMALUM R3 WITHIN NORMALLM TB WITHIN NORMALUMTTS W m iN NORMALLIMITS WITHIN NORMALUM RS WITHIN NORMALUM TS WITHIN NORMALUMITS WITHIN NORMALLANTS WITHIN NORMALUM RS WITHIN NORMALUM TS WITHIN NORMALLIMITS CYST. UMLATERAL DuPont-15261 PEER REVIEW DX M M EE A O R EE AONOI AGREE AGRBI AGREE AGREE AGREE AGREE AGREE a g r ee AGREE AGREE AGRU AGREE AGREE AGRBI 4877 IR 4 6 7 8 IR4681 IR 4 6 8 3 4587 4681 4684 84 WITHM NORMALLIMITS 36 WITHM NORMALUMITS AGREE AGRBI GONADAL STROMAL ADENOMA, 106 TUBULAR ADENOMA. UNILATERAL UM LATERAL 106 WITHIN NORMALLASTS 106 NOT EXAMINED. MMSMO AGREE 106 WITHIN NORMALUM RS AGREE ' 106 WITHIN NORMALLASTS AGREE 88 W ITH NORMALUM RS AGREE 106 WITHM NORMALLASTS WITHIN NORMALUM RS, ONE O F PAIR 78 MISSING AGRBI AGREE GONADAL STROMAL H YPER PLA SIA , IR 4 6 8 6 106 78 WRHIN NORMALUM RS WITHIN NORMALUM RS UM LATERAL A O R EE 4 6 8 7 106 GONADAL STROMAL ADENOMA, TUBULAR ADENOMA. UNILATBUL UM LATERAL GONADAL STROM AL 4688 4688 4800 106 TUBULAR ADENOMA 102 MALIGNANTLYMPHOMA.HHTTOCYTO ___ 2 2 _ __________ CYST. UNILATERAL UM LATERAL A IM M A O R EE 8 30 0 ppm (Group 1)- continued DuPont-15261 WKB ANIMAL* ON T EST ORIGINAL DX PEER REVIEW DX IR 4 6 0 S IR-4U03 IFM 004 106 106 106 WITHIN NORMALUMITS WITHIN NORMALLIMITS CYST. UNILATERAL GONADAL8TR0M AL H YPER PLA SIA , MMMAL, UM LATERAL AGREE AGREE IR-4606 iF u a o e 77 106 CYST. UNILATERAL NOT EXAMINED. MS8INQ GONADAL STROMAL H YPER PLA SIA , M EN IAL, UM LATERAL AGREE IR460B IR-4S11 IR-4612 IR-4613 IR -W 4 IB-4815 IR-4816 106 106 106 86 106 106 106 IB-4817 IR-4619 73 83 64 IR-4821 IR-4622 ....... i 88 63 86 1*462* IR-482G 3531 100 100 106 IR-4627 106 -4 *2 8 1 IR-4634 I 106 63 106 WITHIN NORMALLIMITS WITHIN NORMALLIMITS WITHIN NORMALUMITS WITHIN NORMALLM TS WITHIN NORMALUMIT8 WTTHM NORMALUMITS CYST. UNLATERAL LEIOMYOMA WITHIN NORMALLM TS WTTHMNORMALLM TS WTTHW NORMALUMITS WITHIN NORMALLIMITS W ITHttl NORMAL UMTTS CYST. UMLATERAL WITHIN NORMALUMITS WITHIN NORMALUMITS GONADAL STROMAL H YPER PLA SIA , M EN IAL, UM LATERAL AGREE AGHBI AGREE a g r ee AM H M W w lB S iffc S r 8U 0E, ONE OV 8 WTTHM NORMAL LEM TS AGREE AGREE GONADAL STROMAL HYPERPLASIA, MILD, SRATERAL AGREE GONADAL STROMAL HYPERPLASIA, MILD, UM LATERAL A G R EE A G R EE TUBULAR ADBtOMA, UNLATERAL CYST BILATERAL a m iiiiii m m iiii ADENOMA, U M LA IB IA Li CYSTM LATERAL WITHIN NORMAL UMITS WITHIN NORMAL LM TS WITHIN NORMALLM T S A M IA M t TM U A I H YPER PLA SIA , MEMEAL, UM LATERAL AGREE AGREE 9 31 DuPont-15261 0 ppm (Group 1) - continued W KS ANIMAL* ON TEST IR-4636 iFM se IR-4837 1 1 !^ 94 106 1 68 ORIGINAL DX WITHIN NORMALLM T8 WITHIN NORMALLM T8 WTTMN NORMALLIMITS WITHM NORMALLIMITS WITHM NORMALUM TS PEER REVIEW DX A M liM I KVM IIII H YPER PLA SIA , KM H AL, UM LATBUL AO Sn AOMEE AOMEB ACM ES 10 3>t DuPont-15261 30 ppm (Group 6) W KS ANIMAL! ON TEST 4781 42 ORIGINAL DX -- WITMN NORMALLIMITS 1 P SR R EN /ratfD X - AGREE 4 7 4 4 48 WITHIN NORMALUMTTS AGM B ^^^W gH W N ORm UM TC^^^^ iS H l llif e i IR 4 7 0 6 WITHIN NORMALUM TS AGREE 4707 GONADAL STROM AL H YPER PLA SIA , 90 WITHIN NORMALUMTS-ONE O F PAIR PRESEN T M ILA UNLATERAL IR-4708 108 W ITH NORMALUM TS AGREE 4 7 0 8 98 WITHIN NORMAL UM TS a g r ee 4 7 1 0 106 CYST IR-4711 108 WITHIN NORMALLIMITS AGREE 1R-4712 94 CYST AGREE 4 7 1 3 97 WITHIN NORMALUM TS AGREE m-4714 108 WITHIN NORMALLIMITS AGREE IR-4715 106 CYST. UNILATERAL AGREE 4 7 1 6 108. CYST. UNILATERAL A G R EE -- <S8QBSl -- STROM AL H YPER PLA SIA , 4 7 1 7 10S WITHIN NORMALUMTTS UM Um RAL 4718 4 WtTHM NORMALUM TS AGREE 4 7 1 8 98 IR-4720 106 CYST. UNILATERAL WITHIN NORMALUM TS AGREE -- oSnadal STROM AL H YPER PLA SIA , iB tw in i IN EU TER A L 4721 96 WITHIN NORMALUM TSO N E O F P A PRESEN T IR-4722 83 WITHIN NORMALUM TS AGREE 4 7 2 3 106 TUBULAR HYPERPLA8IA. MODERATE STROM AL H YPER PLA SIA , M ODERATE, UM LATERAL 472 mm 106 94 4 7 2 8 106 TUBULAR HYPERPLASIA. BILATERAL MILD WITHIN NORMALLIMITS WITHIN NORMAL LIMITS STROM AL H YPER PLA SIA , M ODERATE, B ILA TER A L AGREE G O IU M L STROM AL H YPER PLA SIA , MMMAL, UM LAT8RAL 4 7 2 7 106 - H ,, CYST WITHIN NORMALLIMITS STROMAL H YPER PLA SIA , M NM AL, UM LATERAL AGREE 11 33 DuPont-15261 30 ppm (Group 6) - continued W K8 ANIMAL* ON TEST O RISINAL DX P EER REVIEW DX 100 WITHIN NORMALUMTIS AGREE IR-4731 74 88 IR-4732 88 WTTTW NORMALUMITS MALIGNANT LYMPHOMA. HISTIOCYTIC WITHIN NORMALLIMITS 6LYMMAnmGPnHMuOnnKMnnAu " GONADAL STROM AL H YPERPLASIA, MMMftMU UM LATOtAL 106 W ITH*! NORMALUMTTS A G R EE IR-4734 86 IR-4736 106 WITHM NORMALLIMITS WITHIN NORMALLIMITS AGREE flWMAITAI. STROM AL H YKRPLAM A, M U L UM LATERAL GONAIM L IR-4737 sto m a l H YPER PLA SIA , M ODERATE, 106 TUBULAR HYPERPLASIA. BILATERAL MODERATE BtLATM AL IR-4738 101 WITHIN NORMALUM TS A G R EE IR-4738 106 WITHIN NORMALUMITS A G R EE IR-4740 106 WITHIN NORMALUMTIS a g r ee IR-4741 87 WITHIN NORMALUMTIS A G R EE C 3 S S 1 83 WITHIN NORMALUMTTS A G R II IR-4743 87 WITHIN NORMALUM TS QQNADAL IR-4745 106 TUBULAR HYPBW LASA, UNILATERAL, MODERATE GRANULOSA COLTUM OR, BENIGN, UNILATERAL STROM AL H YM RPLASIA, M ODERATE, UM LATERAL IR-4748 87 WITHIN NORMALUM TS ASM S OTHftfN i STROM AL IlYPtPRPt AHA IR-4747 IR-4748 106 61 CY8T, UNILATERAL WITHIN NORMALUMITS u n m t ir a l ; CYST ABRK IR-4748 IR-4760 IR-4782 IR-47B3 IR-4754 IR-4756 STROM AL H YPER PLA SIA , M IS SA L 82 WITHIN NORMALUMTIS UM LATERAL 87 WITHIN NORMALLIMITS AORBI TK7MAIW STROM AL H YPER PLA SIA , CYST, BILATERALTUBULAR HYPERPLASIA, SBVBM , 106 BILATERAL. MODERATE M LATERAL GbHAPAL STROM AL H YPER PLA SIA , M 00B IA 1E, 106 TUBULAR HYPERPLASIA. BILATERAL MODERATE UM LATERAL 106 CYST. UNILATERAL AGREE GONADAL STROM AL H YPD VLA BIA , 105 TUBULAR HYPERPLASIA. BILATERAL MODERATE M HA BILATERAL 12 34 300 ppm (Group 5) DuPont-15261 WKB ANIMAL<CM TEST IR-4878 49 IR-4842 S3 IR-4852 MJA^ 63 S3 83 * 83 83 IR-4671 S3 IIFM 674 > S3 83 . 83 IFM688 83 M-48S3 83 IIER-E46EM! 63 ORIGINAL DX WITHIN NORMALUMTTS WITHM NORMALLIMITS WITHM NORMALUMTTS WITHM NORMAL UMTTS WITHM NORMALUMITS WITHM NORMALUNITS WITHM NORMALUMTTS WITHM NORMALUMTTS WITHM NORMALUMTTS WITHIN NORMALUMTTS WITHM NORMALUMTTS WITHIN NORMAL UMTTS WITHM NORMALUMITS WITHIN NORMAL UMTTS WITHM NORMALUMTTS PEER REVIEW DX aoub AQRBE AORB AORB AM U AOREB AORB AORB A O R EE AORB AORB AORB AORB AORB AORB * IR-4641 73 IR-4643 78 IR-4644 106 106 IR-484 IR-4847 IR-464S 108 106 88 IR-4648 106 IR-4860 IR-4661 B 3EE! IR-4664 IR-4657 IR-4688 in-Aesa ifeteeo IR-4661 IR-4662 1R-4863 104 08 87 67 106 108 106 106 106 106 106 NOT EXAMNED.MI88INQ WITHM NORMALUM TS WITHIN NORMALLM T8 WITHM NORMALUMIT8 TUBULAR HYPERPLASIA. MODERATE CYST. UNRATBtAL WITHM NORMALUMTTB TUBULAR HYPERPLA8IA. BILATERAL. MODERATE TUBULAR HYPERPLASIA. BAATERAL. MODERATE NO DIAQN06I8. MADEQUATE SECTION WITHM NORMALUMTTS WITHM NORMALUMTTS WITHM NORMALUMITS CYST. UNILATERAL WITHM NORMALUMITS WITHM NORMALUMTTS WITHM NORMALLASTS WITHM NORMALUMITS WTTHIN NORMALUMITS AORB AORB AORB SM BPN . STROM AL H YPER PLA SIA , M OOBATE, UM LATBAL A fin H QONADAL STROMAL H YPER PLA SIA , SW fSNEi M UUHAL QONADAL STROMAL H YPER PLA SIA . SEVERE, M LATBRAL AORB AORB AORB A O BE AORB AORB AORB AORB A O BE AORB 13 35 300 ppm (Group 5) - continued DuPont-15261 WK8 ANIMAL ONTEST IR-4686 84 ORIGINAL DX TUBULAR HYPERPLASIA. MODERATE PEER REVIEW DX NDL INOM AL H YPER PLA SIA , M ODERATE, LATERAL NDL STROM AL H YPER PLA SIA , IR-4667 IR-4672 IR-4673 IFW7B IR-4877 106 TUBULAR HYPERPLASIA. M6JD Sj S d u l 81 WITHIN NORMALUMITS 82 VYtTHIN NORMALUMTT9 A OONADAL STROM AL H YPER PLA SIA , M ODERATE, 106 TUBULAR HYPERPLASIA. UNILATERAL MODERATE BILATERAL 78 WITHIN NORMALUMTTS 106 WITHM NORMALUM T8 106 TUBULAR ADENOMA. UNILATERAL A sm A O RES 5N EL---STROM AL ADENOMA, UM UM RAL fft-4679 106 TUBULAR HYPERPLASIA. BILATERAL M ill) STROM AL H YPER PLA SIA , MNDBRA1E, STROM AL H YPER PLA SIA , IFM 680 104 TUBULAR HYPERPLASIA. MODERATE BEAm M L IR-4681 IR-4682 IR-4883 IR-4684 IR-4686 IR-4686 STROM AL H YPER PLA SIA , M ODERATE, 87 TUBULAR HYPERPLASIA. MODERATE UMLATBRAL 84 NOT EXAMINED. MMUHNO AM BE OONNML STROM AL H YPER PLA SIA , M ODERATE, 106 TUBULAR HYPERPLASIA. BILATERAL. MOOERATE BBATBRAL a N IM L STROM AL H YPER PLA SIA , 103 TUBULAR HYPERPLASIA. MODERATE MNNHHALf UM ULTERL 76 WITHIN NORMALLIMITS AflH EB -- STROM AL H YPER PLA SIA , MHMML, 106 WITHIN NORMALLIMITS UM LATERAL 14 36 300 ppm (Group 5) - continued DuPont-15261 W KS ANIMAL ON TEST IR-4688 IR-4000 IR-48B1 IR-4603 IR-46M 108 106 100 106 106 IR-4805 IR-40S8 iR -w or 106 106 106 iR -w e 106 IR-4700 IR-4701 IR-4702 IR-4703 IR-470B 06 106 87 106 02 ORIGINAL DX TUBULAR HYPERPLASIA. MODERATE WITHIN NORMALLM TB WITHIN NORMALLIMITS WITHIN NORMAL LM TB CYST. UNILATERAL WITHIN NORMALLIMITS CYST. UNILATERAL WITHIN NORMALUM TS CYST. UNLATERAL TUBULAR HYPERPLASIA. M ARKS} WTIHIN NORMALUMITB TUBULAR HYPERPLASIA. MODERATE WITHIN NORMALLM TB WITHIN NORMALLIMITS PEEH REVIEW DX STROM AL H YPER PLA SIA , SEV ER S, UNNJLTERAL AOHEE A O R EE AOHEE A O R EE GONADAL STROM AL H YPER PLA SIA , UM LATRAL AORM A O R EE STROM AL H YPER PLA SIA , M HIL BILATERAL STROM AL ADENOMA, UM LA1ERAL AORM A O R EE AOHEE 15 37