Document nk1jgJb99ZrVGZOV6kBRavrg1

Study TMe FC-143: Two Year Oral Toxkct-Oncogemcity Study in Rats PEERREVeWOFOVAME8 APEPOexutptehBeroroCirm*s.4Me7na4tanlnP,aDth.Vol.Mog.yLaboratories, lac. (EPL) Herndon, VA 20172-0474 BHESt.laekLsvtkoedennallRRPLo.oaFanbdrtoa,drmPae.teNoO,reDy.mBf.VooorxaJHntSieO,eaPnlhtdhJCXaonmd Epannvyironment! Science Newark, DE 19714-0050 TestGuUeHue:Not Applicable Dads Completed: June 25,2004 LaboratoryProjectID: DuPont-15261 Work requestNumber: 14459 Sendee CodeNumber: 1243 Subm itted B y: HNEE.leakLwstkodaenrnlklRP,LoDoaanbEdto,drP1ae9.tNOo7r1e.yB4mf-oo0o0rux5Hr5s0e0aanldthCaonmd Epannvyironmental Science A u th ors DuPont-15261 PVeetteerriCn.aMryuPmath, Dol.oVgJis&t ,DiplomateA.V.CP. Date * 0 0 4 ________ Steven R. Frame, D.VM., PhD., Diplomate .V.C.P. Principal Research Pathologist and Research Manager, Pathology Date 2 DuPont-15261 FC-143: Two YearPOerearlRTeovxiekwttyo-fOOnvcaorgieesnidty Study In Rats TRDPoLrhhaaiip.begtDsloisnw,rlmiaaDdetlaolreiypetrseilpee,fxresAmoa,emmmIrantreiectenhr,.vie,Aecid3eaomMwnavneCea(rddrPioicreblraelosyenpjgfoetCrwecortotomoeNldflveFVubegCmtyeee-troDeb1irn4efriVrn3a. rRa:0eyrT2otyep8wbrPa1eiotnaCrhttaYRohGrOloyeoealOPgoirl1igaOs(2titshs)srt.to:auslPldToaTeynhgtodeipesxraptSistCceht.iee.otTvyrMlheo-rOenegavsinRnsilnceti.)d,owFDefgosfeaVorwnmcRMiecueiri,,skteeyDedrS.Votun.Mdy.,in ptigonrroatdhdliiaiefnegfgrnoa,oltalisovstwiewcilnenelosglimoaresnepsninocotrlefatrttphurreeeotaavntaidorync.roiTtfethrhieaepapeneederrrrereeavvcieihewewdpfaaignthrdeoienlomggsei.nstTtschdmiisslceausgisroseneedmdiieasnsgutneiosssrereesfllaaentcedtded Materials and Methods rAdptnbeAtpwhehveiaoevalpoeelatelnogheipslresdeukwneoelwraaisonolead.tot.vdsoafniegeoTiitniasxehismnshrwsle,aAteieta,ssnaulste.eotnsdhdeevhvadtpyedtahinahatpliartiahuernhmiestaeeacopetdsastalesierueivlodfeeesrdransedrociheiavsnlramdaama,eitsedfobtvtehteawhleisateeeoohrfnwywdebsvoSyweiywhas3adperesgfeiwiararoaenaornecegseenolirtienmiwssnihfmfktioeoeiuseascrsatdrlpaieeoslesityssednniwnlvetcfpiahsosoreelattutarrtrutelteedtheathddvidesovneiyiidieaaloeoe.iosinowidtnTlgn"aptvsheioAbprtasirehneltanrigemsiweatoerhetfnerhsrenooeiseebrmftrlap"eooeapoc.oamgrftrveFrloiiefsteafsoaroiairrtntedcrecihrageeet5hetaghsio3vaatmraeinveirdnnwepedaeiaiwedumeeinoledeir.aawtapafkhbTlorlfyosiellnohtaeyssrhoeerieofstdnesthioorhenogoserrbaeitifitffetugividoshnafadietaeosninulynt.traipada,aeSilleynalyi5ennso3rdicrse, Criteria for Diagnosis of Proliferative Changes in the Ovary mwTcasIanhadphhaosdpticiebusiecrstelahigo,dornovtinhtnsnoeo,eosarnlsmitfduoceobatutarecelpmllaeasdarltrlergligcvasosileaegnammlcnnnglsuataodoloyimssnvce,lbaahabdiernyraucyactnateosyogtprmpthesofprteerppeioyatrlamlitaeiahrsfsslo,ieamengrsvrneael.etatthnTcsinaeveohadselcoseuschvc,emsaahaanmbralrntatoinahacacvlgroontleeearugsrspcnglti.haorsdhotnarihamtncdhagslfaev,ei.netllseTiaenaaathgetrsdeeedreresanrbevnctooyeeu(rlllllmiucolafsuptoream,brilafmonfloa)itoyadoacrmahpeialnpalygcltveseieaaenrmlprlsgaapsta.rinetyaIcaintareasal.l,ssngoIaocnlmnaedneds. oPcc(Dalbraotsiesxelsgirofiovfenierreyadedttiiinavancsle,tlehul1eiedt9sheo9ioesv9rnl;aeesrPspi(ieeiohlstuyhnfspesroloeciramoaplnm,ltadghpsoGeoianscoaeourdddrraronolenefnso,tgtrp1rsoal9tmaun9sdu2aiay;llo)A(wssinaelei,txsrrteoihcnnaeosclreildcatgl-at,sooLltnur,toaht1emde9aaa9olll0ovs))taror.rosPryemgrraotearolrelimlfiige-nlreciaonketreeliilvrgcaieinelnllly.eolssrT,iiogohnirinss 3 DuPont-15261 mixed populations ofthese cdl types (Dixon et al, 1999; Peluso and Gordon, 1992). ft hrThiayshskpub,estre,upefmlonarsorteirhacsioasdmnepdrmeivgeereondrndeafvedrdioaemflwlsa,tgrhtoofynmopardoatlahpaleldaspetsrnuioaormpmaonaasdl,ecnrseeeolsolpsfpeablcnaetsaicivlayoesmwliyseb(ariPenneeddlduieas(vgPoanelaolunusadestodiGoaanonsroddgfooGcnnao,arrdc1dia9onl9nos2,gt)r1e.o9nm9ic2a)l. ntHG(uionyobtcpnutraehleadreaprasnpllianorssogrtirmfaogiwlmarealsaadlsuolethgfewyrsaatpilrtdeohcermedipnlllafcasrl)rsoceifmaeaolsirlsim1sn-pwg4rd,esiitdssihzeceenrop)eter.twnewdohiiternhndgoituofhftneuatsinhneeitanerrcreesrlateaisattiiscaveolenianstniazfdiine/boiornrofgsufeeosrntecolopalinrrfgonoeleridmcfetcirvclaueetsiltoltisesnrs(sbuoue.tr Thdbpsdcfgoooyiroioyaaimrrptnmpgghrteaeihenncardasweooparpdasssyllholeelaeiysancnssdl,t,troiedraitiatsmosthhferifmteotebrraohoirnicaoaetemasrlrnnabiadlitdrerndgoeiyesahiroduifmifnnoytufaeeoanpadeaerdsetetsesdeauritd(nrepnalcrtoeablagsoiaatnrllmforsiteostciifehnabhyfmtveigiewptenaoadrllhleoelleduofdy-ssaaodguipedhtoriisineemyconigrtnnapn,spoeolgeolnibnmafrsntaesapshligdaasilyoeaa.etraunestdlflThariaOrsaeoolethtexsrmnsaeoaritnmrzdfhmtedtoheeuaif.eacanoamtlrnodrtdGooeaoem3is,dtsonracmt,teanooioltnnawmmhipoagndeeamaluad(ls)aoDolid.assrbsweehistijxresncegofosoccboomsntreamrindvesaosaeeeetloddfdn.aamap.tdlplIr,eoeSofrs1niftcailmr9nioionofn9cmenamc9aersrinaa)iiads.lsstiilyiemtzvaTenoerenahcenliceisshytdhtahiaedneta ModHchifoaaatgwhnnnyigesoveossseetfruwdt,hdtedoeyrueocerovndinnsaiagurtgairaeiennsroteodhsdueiaadtvtginnednerouoyersssiveunmdabgltwaulfleoalittedaihoorreegnsaveo(si-nDeeoawfidffx.eapoclrntoswtelritofaeamsrl,aoatv1lioe9hrn9yl9opw;oePhkrpieeclldhau,sswaioaloladupnuloddrsinGpsigrbootlrbhedaeopbnprlo,eyle1infr9oe9rrte2abv)t.eiievwe hInycpiedrepnlcaesisao/afdpernoolimfearactoivmeblienseiodn) sw(egroeneavdaallusattreodmbayl thhyepCeropclahsriaan,-aAdremnoitmagae, torrend test and the Fisher's exact test Statistical significance wasjudged at P <;0.05. Results tTATrooeIi(hnenaxffhapfescatdablephiemaidlelnepelcpeaeintrtrpntoene1eadheerrdc.stisiaisdxeemgRirisnnospinAncaonseiteeta.nahfrssalTcoeogtfscsruhovrfaifthdofueeeacaiyugderrlcoiliintpryebafrpotci,inerhacguriweyoldeaplispenodleetoiotsanntrfhaiheerlrdcoateterrennttafte(hhnloSosotpeieueticbvfocbmccoaogertisoutsnnon)lbnereasneeaerdsnsk--eanriiyyiidddooomd,eeaennbf1aavlrasearr9teaslhfnsid(i8trnon5reii7foHmetr3o)toeemash-rrartwtesiilwahrmglseilioe/isgheghnvksiihkryanaca"ot)lprhctlueifyimreennorpirsafitoirp,miecmoctalroruaesifoosvmsm,isganinaaaccgiordssvoryaragiiwepnvfcdwrniidioreccedia/iluevfeouslsi.pevcraaTaslealTsaovabrldirphuabasaaeemiatlstlnssetasnehioeibod1utosmnhln,mweotpaiacsnrftbnTeaiodlenfsinherorineseitbreosnhsedTetnfevitepesiaufiotdxeornamviwtuiniomnabn.r5rediat0erolss 4 DuPont-15261 Incidence of Gonadal StromaTlHabylpee1rplasia and Adenoma in Rats* Dose No. Examined Hyperplasia (Total No.) AAHddyeepnneoorpmmlaaasaian_d_/_o_r _----_GGGG_rrr_raaaa_dddd_eeee__243l 0 45 8 62 004 12 4370 16 7 3051 16 `Animalsonstudybeyonddie interim(53-week) sacrifice 300 46 1563215 17 gmTogresceivrrrrhgsoooihitepndurueyreeieprpepfcin(i.saewcttc,ihraFveerepaneseoorlttstlearaypifssbena)iei,nx.altocigca/3stHasirmrh0vdtaeeao0edaepdtwlnseiplyseefoep3t.o,dimvmci,rTlen4aeaarch(,ls,dcliPeiotydeoor=inreemnsnnoaa0icggtbcdm.imne0drienaasnie4efedonodni6decmcitfad-afeiprnnaonsenr)tdroltooaiwrpln0etftirefacao.lo0eedsrtclere4sic4paidaf8uotr/esi4ogrnrfev,ao5grsseaotrr,ioi6selnvndesf/piesi4nshgesiil7cyoroecCaipnsnadodoiesnemooecrdndnphf3picslpa1raeaaagwr1rssnnoen/ioa4addloAis6ff(staerotoaebiomrdndboactesaiwttvotenihlaenvroniegvtetwmurhee0olmedeaaa,l3rssnbiweg.i0ndoerSse,rantFtor)haads,eimntesetaihhdosde3oitegei30tfrchnh00'3aseoe0lpomstsppetriszampintsem,, controls. Discussion and Conclusions pTrceoehvereirreesrwslepivdeodieneswwdoeipdfthoattvoehmaotrhlipoeehsgdaioissaiftsgsrnoaaotnsesgpeforrsoonomlaiffdetaaurlabtwstuitvroloae-rmylheeaysaliprhofenyerspepdeolarifnspfiglaeaseostioruavtdouayrbrwygu.oliatnLhraaeFddsaCielon-sn1ot4srmo3dmaiwabagelynraoetdhspeeeendseotbrumydaythe ppdcnsduhaaioearttasmhhgfinagonoegcnollneeooascsggteelioaiidposstbinuttbtssh(ryoeoewerf,ntlvheitgeuuereomedbgnsubritaanTualdnaadstaruhteyhlhldeoespytropsarptaronthehocmrmaolepinlafllooelalfrgrtrsleuaoeiisatrmsmiteivo)oc.oeornervTalsn-edaatbhslreteiyeiynoatdpotpnneiumseasr.bgtorarlnFeoifwsfoumghlseoroettacuhindlctleeadcntrddeemosalrdumllmosigse.regtsernseuo,cpsbsmletaeacatadsutnlerbrutdeouym,romitanghonoiecdnfrum-ptfwrheroroeeaermrsnpmrthaeoodloBvvrilOiaeoaeggrwgniieaconnsetricic Etoxtcheopstefoorfddiifefeorreignicneaslisntuddiaygfnoorstthicen3o0m0 penpcmlagturoreu,pr.esMulotsreodftihspeapraetae rreesvuieltws owcecurerrseidmfiolarr the control and 30 ppm groups wheremore hyperplastic lesions (irrespective ofthe 5 DuPont-15261 nohciganooydrfcomnpetrhunteereeporaonpsmpslc.lseeala.aesisntirSuaoros,receima*czdurueeteseroneerwevdof,dis)mtdthiwrenaoen,ermgocrereeraewoloaaldebtfeeresiserenniorinocnvnrmoceesidasa,dtswabeaetnnydiascdsftleieehocsseybaiiUonpspeneeytrrehvgpsreerilrgaadcednsoviieinnaif,eitctwcwrhooaehmlnpig3tacbitr0hnhio0ncowueprlpdooepatguimhsnilsadettgnscrrei.oionnaBrutrgeepaeoidss.tnephgHdaoerdnorooaduwonlptfetsoshttvhrreaeoeernrml,tearsateiulavltetesdto References RASLlai,stSoAnwcRaedHlle,mMMiRco,PrMgraeonssnK,tgSToa,mnanDerdiyeMgJroo.,nCptpgA4o,2ma9ne-dt4y4MJ2ra.cCkAcn(r1ic99W0)F.,O(evdasi)yP. IanthBooloogrmy oanftGheAF, Eisuhsetris PDInri:oxGloifnueiDrdae,tsilvefeionlreiTnsigooxenirscJooRlfo,tghViecaOlPeavritaohroyMl,oUGgy,teJ.roSuhTsn,PsV/oAangRAiPnNa/A,,CSFIteaPrbv,iWinxsaeldsnhdLinOGgvtaoindndu, cDFtrCiint.hRCaHts.(U19R9G9)-.5. PIILne:SlMuIsPoorhJeJrsUsa,n,WdDGausnohgridnwogontortLnh,RDD(LC1,9,a9pn2pd).3C5Na1pr-a3emn64eC.oCpl(aesdtisc)aPnadthNoeboioplloagsyticoCfthhaenAgegsining tRhaetO, Vvoarly1.. FSInliucb7oin3rodMcdh,CeLmoJmi(c1pa9aln8Fy7C.).-1T4w3 oinYReaatrs.ORrfallc(eDrEiextp)eTroimxiecnittyN/Oo.n0c2o8g1eCnRic0it0y1s2tu, RdyflcoefrLaboratories, 6 DoPont-15261 7 DuPont-15261 WKS ANIM AI. O N TBST 25 M ao? cm - 52 55 SS 1 IM B W 1 BO Tl Cm 68 SS 55 En 55 55 [ IfMOOQ 1 cm in - M aa IR -4530 IR -48 81 w aaa 83 SS 55 55 55 65 55 WMMO 0 ppm (Group 1) 0R T0M ALDK W im m N O M IM . U M T S MAUW ANTIVMPHOMA, LVMPH0CV11C VW1HM NORMAL UMTOB WITHM NORMAL UMTOB WTTHM NORMAL U M T S WTTHM NORMAL UMTOS WTTHM NORMAL UMTOS WTTHM NORMAL U M T S WTIHM NORMAL U M T S WITNIN NORMAL U M T 8 WTTHM N0RMALUMTI8 WTTHM NORMAL UMTT8 WTTHM N0RMALUMTTS WTTHM NORMAL U M T S WITHM NORMAL U M T S WTTHM NORMAL U M T S CVBT. I|M5ATERAL PSE R REVIEW DX AORBH MM AORBI AM BB AORBB AORBI AORBI AORBB . AORBB mn AORBB AORBB _____________AORBB_____________ ra cm cm M t HM 8B$ trabst H 651 tfW M fi IR -46 05 IR -4 5 0 4 IR -4696 cm IR -4 5 5 7 5 WTTHM NORMAL UMTTS 5 6 WTTHM NORMAL U M T S AORBB AORBB QOWAPAL STHOMAL 105 105 105 105 105 SO 105 70 TUBULR A D EN O M . UN&ATBTAL WTTHM NORMAL U M T S NOT BtAM M M L M M N S WTTHM NORMAL U M T S WITHM NORMAL U M T S WITMN NORMAL U M T S WTTHM NORMAL UMTTS WTTHN N O m ilA L L M im ttM PAIR UM LATBIA L AORBB 5R R -- AORU jm n m QONADAL STROMAL H Y PB R PL A 5IA . 105 WTTHM N 0RM A LU M T8 UMLATBRAL 7 8 WITHM NORMAL UASTS AORBB QONADAL BIROM AL 105 TUBULR AOBIOM A. UNILATERAL UNLATBRAL QONADAL BIROM AL 105 TUBULR ADENOMA 102 MAUQNANTLVMFHOMA.HWTTOCVTKS w CY8T. UMLAT5 RAL UM LATBIAL A om 8 0 ppm (Groap 1)- continued DuPont-15261 WKB u m d N frar omaoMLDx 108 JfiSSS. 108 Meo 108 WITHMNORMALUMTIB WITHMNORMALLRBTB CV8T. UMLATERAL HM80B 77 IR-<808 108 CY8T. UMLATGRAL NOTEXAMNBL MMBM8 F B I REVIEWDX QONADALSTROMAL HYFBRRLABM. UMLATTBML ABRBB QONADALSTROMAL IIYRBRRLABIA. UMLATBRAL OOMMMLBTmMAL MB HMS14 IR-481S M eie 108 108 W 108 108 HM617 H iie EZST1 78 08 84 M en yi im 08 00 08 4M 4 n iA B i 100 100 108 HM8S7 108 WITHMNORMALLASTS WITHMNORMALLBSTB WITHMNORMALLASTS WITHMNORMALIASTS WTTHMNORMALLASTS VnmONNOMULiJuna C W . UNLATERAL i am iw n u A WITHMNORMALLASTS WITHMNORMALLAST* WITHMNORMALLASTS WITHMNORMALLAST* WITHMNORMALLASTS uS S S m l ABRBB ABHHB ABRBB 8UOB.ONBOV WITHMNORMAL LBMTB ABRBB ABRBB OONMMH 9MMML H vnw uaiA .M Lo, ABRBB aatmm. GVST. UNtATERAL WITHMNORMALLASTS WITHMNORMALLASTS wwhbmlabm ^ UMLATBRAL ABRBB QOMABAL81W0MAL TUBULARADBIOMA. UNOATBIAL UNBJOBRALj CVSTBRATERAL CVBTHLATBRAL QONMm ^ rm ojiA L 108 WITHNNORMALUMTTB ^ J 8EH fllu-- 88 WITHMNORMALLASTS 108 ______ WITHMNORMALLASTS______ 9 01 M OV HMV MOT N 0V -- -- ^ tr VHW HM AN im o u u rw am o o rn m o B sm m -- l i i M ain m iM sD R rrm B sn ffi R -- s im m s a s m m 5aB m * araB B -- tt tti w 61 M XQMOA3U tfB d xaivM M O T SBEIMW pM iapw - (f <faKU*>)mdd o w bi Mrcn "ZBW Ji "5S F B T M i 1VNNV WSI-WOJW WKB a n m a lJ DNTBffl IR-47B1 I - 48 47441 4$ 30 ppm (Group 6) 0M M M .DK ---- VWTHM NORMALUM TS WITHM NORMALUMTS DuPont-15261 PEER REMEW DK AOHBB 470$ IR-47M m-4710 4711 4718 c rs n ra i rzm 471$ 4717 471$ 471$ 4780 4781 4788 4783 4784 478$ B P" ... -- STROMAL HVPBRPLAMA, 0 VWTHMNORMALLEETM N E OP PAM PRESENT M EJL UNEJKTIRAL VWTHMNORMALUM TS AORBB $$ WITHM NORMALLBflTS 10$ CYST 10$ VWTHMNORMALUMTS AOHMI IM M $4 07 VWTHMNORMALLOOT* 10$ WTTHMNORMALUMTS 10$ CYST. UMLATCTAL AMMS SORBS |M M 10$ CYST. UNKATRAL AflM B d S fiU A L STROMAL HYPERPLASIA, 10$ WITHM NORMALLM T8 unE S S a l 04 VWTHMNORMALIM T S 00 CW8T. UMLA1BIAL | H M nam L STROMAL IIVPBRPLABIA. 106 VWTHMNORMALUMTS 0$ WITHM NORMALUM TSCN EOF PAR PRESENT 63 VWTHMNORMALUMTS IM U 1SR A L AMRM A SR EE STROMAL 'K B s t H ,* 103 TUBULAR HYPERPLASIA. MODERATE UN8A7W UL IS U m i STROMAL HYPERPLASIA. 10$ TUBULAR HYPEAPLAaA.BLAlBIAL.M RJ> 94 VWTHMNORMALUNITS S S S era l IR-4728 106 VWTHM NORMAL UM TS h v m S l m ia , u f iS f e MMMm L STROM AL^ 4787 10$ 1 1 3 7 1 .- 6 1 .. CYST WITHM NORMALUMTS IM LM M RAL AM U 11 DuPont-15261 30 ppm (Groap 6) - continued WK8 - mANMALI ONTES! IB 4 WW7S0 74 IR-47S1 IR-47S2 108 IR-4734 SB wm 106 ORNNNM.OK .WITHMNORMALIM T WITHMNORMALISAIS MAUONANTLVMPHOMA.HMT10C7TIC WITHNNORMALUMTT8 WITHNNORMALISAT WITHNNORMALISAT WITHMNORMALUMTT8 PEERREWEWDK AIM E AEREE LVMPHOMA --- W f i -- STROMAL HYMRRLAMA, uSSSSMm. l ---- STROMAL STSEnSuL WWOAL M-4797 EV4740 I IA-4741 W746 M-4746 " sO T 10 WBLARHYPBVLAliA.LATERALMODERAT! 101 WITHMNORMALISAIS 10 WITHMNORMALISAIS AORBE un 108 WITHMNORMALISAIS ABRBE 87 WITHMNORMALISAIS as WITHMNORMALL6AT8 07 WITHMNORMALISAIS guSOSnBMl TUBULARHYKRRLA8M,UNLATERAL MODERATE HVfSSuWM, GRANULOSACELLTUMOR,BB6QN, 106 UNLATERAL unE K s l 7 WITHMNORMALLSSTS mmi IIYPEHRLABIA, IR-4747 10 u s a i 01 CY8T. UNLATERAL WITHMNORMALISAT uiS ktbrlCVST STROMAL HVNRRLAMA, IR-474S r n s n 07 WITHMNORMALUMIT8 WITHMNORMALUMTI im Z m em l ' l^IAfrAI. IR-47B2 IR-47B3 IR-4756 HYEERMAMA, CV8T, BKATBWLTU8ULARHVPBWLA8M, 106 BtATBRALMODERATE S S ! . -- ^gtlMAL STROMAL HWTEWLAMA. MODERAIS, 106 TU8ULARHVPBVU8IA.MUTERAL MODERAT! UMLATBIAL 106 CY8T. UNILATERAL S S r STROMAL II7EERELAMA, 106 TUBULARHYPBVLA8M.BILATERAL MODERATE MLDlMLATERAL 12 WKB ANIMALI ONTO! KM67B ----- IR-4M2 ? a IR-4666 53 JmS SimB . S3 cm HBJBflt II1MIWM tt a S3 cm a C T 3 1 S3 c m S3 MW S3 iiMeao S3 iw w a Hwe S3 300 ppm (Group 5) ORIGINALDX WTTHNNORMALUMTT8 WITHNNORMALLOOTS VWTHNNORMALLASTS VWTHNNORMALLMT8 WTTHNNORMALLOOTS VWTHNNORMALLMT8 VWTHNNORMALLMT8 WITHNNORMALUMTTB VWTHNNORMALUMTT3 VWTHNNORMALIM IS VWTHNNORMALUMfTB VWTHNNORMALLOOTS VWTHNNORMALUMIT8 VWTHNNORMALUMTTB VWTHNNORMALUMTI8 DuPont-15261 PEERREVIBNGX A0RBE AORB AOMI AORBB AOMB AORBB AOHBB AORBB AORBB AORBR AORBB AORBR A on cm cm cm le m m i mo cm cm 106 103 S3 N0TEXAMMD.MM8MO WTTHNNORMALLASTS WTTHNNORMALUNTTB WITHNNORMALLOOTS TUBULARHVPERHA8IA. M00BVATE CYST.UNLATERAL VWTHNNORMALL00T8 mm AORBB AORBB AORBB --'~ 3 3 S ^ m l CTTIOMAL UVFERRLAIIA, MOMRATE, UNLATBRAL AORBB AORBB VTROMAL HYRBRRLABUL, IR-4648 106 TUBULARHYPBWLA8IA.M1ATOAL.MODERATE BBATBML IR-4360 cm IR-4368 IR-4684 o u te r ir -m sb iiz c y BTMMAL HYKRRUjNA, 104 TUBULARHYPERHA8IA.BEATERALMODERATE b e S S r a l NODIAGNOSIS.MADEQUATESECTION _ _ j g HHL__ 37 VWTHNNORMALUMTTB AORBB S7 VWTHNNORMALLBBTS 106 VWTHNNORMALUMm AORBR 103 CYST.UNLATERAL 106 WTTHNNORMALUMm AORBR AORBB 106 WTTHNNORMALUMm AORB___ 106 VWTHNNORMALUMm 106 VWTHNNORMALLMSTB id im 106 WITHINNORMALLASTS AORBB 13 DuPont-15261 300 ppm (Growp5) - contiimed met AMMALI 0NTBB1 OMQMALDX B E E S EMBUEBE# IW STROMAL HYPERPLASIA, MOOERATE, 84 TUBULARHYPERPLASIA.MOOERATE m^n Om l WW7 1 1 IR-4670 88 TUBULARHYPERPLASIA.MND WITHMNORMALUMTTS VWTHMNORMALLMTB tmOMAL HYPSRPLAMA. MLATBUL AUREE a er es STROMAL HYPERPLASIA, IR-W72 HMW IR-467S -W7 106 TUBULARHYPERPLASIA.UMLATBMLMODERATE 78 RIHM NORMALLMTB 106 VWTHMNORMALLAEIB MATERIAL AEREE MM1 e S mEaL STROMAL 106 TUBULARADENOMA.UMLATERAL uS S S mSm. EMA0AL STROMAL mrPERPLAMA, 407 106 TUBULARHYPERPLASIA.BILATERAL MHJ) hum m l 8TR0MAL HYPERPLASIA, IR-4680 104 TUBULARHYPERPLASIA. M00B1ATE STROMAL HYPERPLASIA, BM6B1 87 84 TUBULARHYPERPLASIA.MODERATE NOTEXAMMED.MMSMO S E S S I AERES AAnABn i. mma ^'w S hrmS ^ 106 TUBULARHYPERPLASIA.LATERALMOOERATE la tb u l oiwbL hvpS mlama, IR-4684 108 IR-MS8 7 TUBULARHYP0VLAMA. MODERATE VWTHMNORMALUMTIE uS S S S ral STROMAL HYPERPLASIA, J&SSH. ___________ VWTHMNORMALUMITB___________ UMUmSML 14 DuPont-15261 300 ppm (Grosp 5) - contened WKB ANIM. ONTEST whom KKWlH-IWM'JOIl IfMOM 10 10 100 10 10 immn 10 10 10 IR-4698 10 08IR-4700 WM701 IR-4708 107 IR-4708 __1s0__ ORKWMLDK TUBULARHYPERPLASIA.MOOERATE WITHMNORMALLMTB WITHMNORMALLMTB WITHMNORMALLMT8 CYST. UMLATERAL WITHINNORMALUMTS CVBY.UNLATVIAL WITHMNORMALUMTIB CYST. UMLATBUL TUBULARHYPBRPLAMA. MARKED WITHMNORMALLMTB TUBULARHVPBRP1AMA.MOOERATE WITHMNORMALLMTB WITHMNORMALLMTB PEERHEVMWOX STROMAL HVPERPLAMA, uhE hbul _ _ jAgOgRMgI_ _ AlBRBE STROMAL HYPBRPLAMA, UMLMMML . AMRBB STROMAL HVPERPiAMA. ML&jMATMML BHTVfltlY STROMAL i SASMMS al AOREB 15