Document p2rg8ygRw0Ze3jmZob6G4k28D

@HwAisZELRENTEOLNN AR 226-0449 Sponsor: st. pa, Himesots FINAL REPORT Study Title: 13-Week PDoireutoatroyncTioaxniocTaittoey.dSt(uCdRAyaStwsNia.th3T6-2551-82061,1)Ammonium DRaetiiaqdueiTrineeme$2n.t1: Author: Matthew J. Palazzolo, PhD, DABT - Date: May 17, 1993 PerformingLaboratory: WHaSadz5il0se1otnoK,ninWWgiimssaccnoonnsSisaniu.nt,vSaI1rndc0.4 wr 6323-100 LabPo rojr ectaIdet ntio ficr atiy on: Vou 1 0F 1 Page 1 of 657 ; 01766 HHI 6329-100 COMPLIANCE STATEMENT 13-WeekPDeireftlauroyraToocxtiacniotatyeSt(uCdAyS wNoi.th318-2551-8206,1)Amoniun in Male Rats AHaTzleatsopnectWsashoifngtthoins, stInucd.y, twhearteweirneaccacrorrideadnceoutwitbhy HthaezleEtnovniroWnimsecnotnaslin,ProItnecc.,tioannd Agency Good Laboratory Practice Standards, 40 CFR 160. DiplomeawA te,J. As f l DSitruedcytoDrirector THaozxliectoolnogyWisconsin, Inc. L. iE 3 To the best of my knowledge, the above statement fs complete and accurate. SEpYonsor's Representative Date -- To the best of my knowledge, this report is complete and unaltered. pWwpTicant -- -- ate 2 - 01767 This Page Intentionally Left Blank HHI 6329-100 3 - 01768 QUALITY ASSURANCE STATEMENT HW 6329-100 13-Week Dietary Toxicity Study with T-5180, Amonfun Perfluorooctancate (CAS No. 3825-261) in Male Rats LtTdahheebenotrQrafuetapioloeirrstytyaPfnrAodasr/csotutrirhciaedsnecseSscttrUauinndbiydet,asrdwosiftthehaH3azatluhsteeehttooernfxoczrWeetipdhstciomoiennntshi4oon0fd,'sC.AFpIRapnnced.n1,d6Si0tx.ia3nn5Ed,auc(r0ch)doarsdG(rab8)anercecen7ii}wrniegtvhiTPeowrtnehedecbroeGiycooeoncdty tsfthoueldlyofwoaeldnldowiihnnagsthseiunbscapoientcdtutecidtonwsorfiotftthetenhesrteutpdeyos.rttisngTohfefahcQiuelasiletiiteyIsnAsuspsseeucdrtainofcnnestUthoneittchoenhdausccitadleosfoD1ctoMhneidsstuocrt.ed WarcictotredningstatotusHazrleeptoorntsWiosfcoinnssipne,ctiIonnc.s, aSndtanfdianrddingOsperaarteinsgubPmriotcteeddurteos.Management Date of Inspection 02/20/90 Lyeof Inspection Protocol Review Date Issued to StudyDirector 02/20/90 03/02/90 Protocol Amendment Review 03/07/90 : 12/21/%0 Body Weight Measurement 12/21/90 12/21/90 Food Consumption Measurement 12/21/90 12/21/90 Animal Observation 12/21/90 01/02/91 Test Material Preparation 01/02/91 01/02/91 Sample Analysis 01/02/91 01/02/91 Test Material Administration 01/02/91 01/02/91 Prepared Test Material Dispensation 01/02/91 01/14/91 01/21/91 01/24/91 02/12/91 03/25/91 ouyas/s1 Protocol Amendment Review Protocol Amendment Review Clinical/PharmacokineticSampling Necropsy Data Review Clinical/Pharmacokinetic Sampling 01/14/91 01/21/91 01/24/91 02/12/91 03/25/91 ou30/m 04/30/91 Data Review 04/30/91 05/16/91 Necropsy 05/16/91 ` 01769 DaItnepofection 08/23/91 07/22-26,29-31, 08/01,02,05-07/91 09/13/91 11/18-12/04/91 11/20-12/04/91 09/28/92 02/19-24/93 03/23/93 04/08/93 QUALITY ASSURANCE STATEMENT IvIenesopfection Histology Operation Data Review Special Analysis Data Review Report Review Protocol Asendsent Review Report Review Protocol Amendment Review Report Review HI 6329-100 StDautdeyDLisrsueecdtotro 05/23/91 08/07/91 09/18/91 12/05/91 12/04/91 09/28/92 02/24/93 03/23/93 04/08/93 gL p. NA RepresDe.ntBaotlilvien,g Quality Assdrance Unit 5711/93 Date s 01770 HI 6329-100 STUDY IDENTIFICATION 13-WeekPDeireftlauroryooTcotxaincoiattyeSt(uCAdSy Nwoi.th38T-2551-8206,1)Amoniun in Male Rats Test Material Sponsor Study Monitor Study Director Study Location StudyInT-iLmiefteabl(eExperimental) Start Date EIxnp-eLriifmeenTtearlminTaetrimoinnatDiaotne Date 7(1C-A5S18N0o,. Am3m8o2n5i-u2m61P)erfluorooctanoate TMoxicology Services SBtu.ildPiaunlg, 2M2i0-n2ne-s0o2t,a 3M551C4e4n-t1e0r00 Roger G. Perkins, Pho, DABT TBuoixlidcionglogy20S-e2r6v-i0c2e,s 3M Center St. Paul, Hinmesots 55144-1000 MHaaztltehteownJ.WisPcaolnaszizno,lo,incP.hD, DABT MPa.d0i.soBno,x 7W5i4s5consin 53707 (608) 242-2622 H33a0z1leKtionnsaWainscoBnosuilne,varIdnc. Madison, Wisconsin 53704 MDaeycem17b,er192901, 1990 May 17, 1993 6 C01771 Toxicoloay MDiaptltohmeawteJ,. APBaTlazzolo, PRO SDtiurdeyctoDrirector JSatnuidcyeCDo.ordMiannaetkoer ToxicoloayOperations Larry Giltner GSramopulpe LCeoaldleerction GRroobuepr,tLKe.adeYroung Rodent. Toxicology Shane Eith SGurpopuoprtLeaSdeerrvices Compound Preparation GDrioxuipe LBeuasdheere LaboAnrimaa)Vteteorinrariyan CDiipnldoymaJt.e,CarAyC,LANDW Clinical Pathology RDiopbleormtatLe., HaAlClV, DVM, PhD Clinical Pathologist WN 6329-100 KEY PERSONNEL ClinicalPathology (Continueg RSounpaelrdvisKoarrkevitch fnatonica) Pathology ATnhoamtaosmiEc.a PaPlamtehro,iogPihst GDreonnuips LeHaodfefrman Necropsy' RGircohuaprdLeaBdeecrker Histology AGnrnoeupMoLsehaedrer Pathology Data Bariculturs) Chemistry HHaannadgaerA. Tshabalala, PhO Methods Development Lmunochenistry JSuopaemrevisSoartyanarayan QualityAssurance Sherry RW. petsel Manager 7 - CoOL? contents OL10E F 11 COPLIANCE STATEMENT QUALITY ASSURAKCE STATENENT STUDY IDENTIFICATION KEY PERSONNEL ABSTRACT OBJECTIVE REGULATORY COMPLIANCE HAINTENANCE OF RAK DATA, RECORDS, AND. SPECIMENS TEST SIMtdAoeTrnEatRgiIefAiLcCaotnidointioannsd Characterization SRaefseetryvePSraemcpaluetsions TEST TISedYseStnTtEiANfniicmaat)ion STUY oeston PROCEDRDeoUtsReeEnStPorenparSaatmpiioens AcDDoocsseefmAAadntaaiilonynsiesstration AHBoondutyseimnNogeritgeannntdsObMsaeirnvtaetniaonncse HTFEooSroTpdonRCeaotneAsrnuiamlapyltsiioRsnesidue Analysis cAStlnaiatntiioscmtaiilccaal`lPaPtAahntoahllaoyigsoyeary WI 6325-100 pase 2 . M , 12 u u 11 111 %15 18 15 111886 hi7 1II8e 111856 11199 coL773 WI 6328-100 CONTENTS (Continued) Page VROeLsUtMsoE1seOFAInaIly(sCeosntinued) Real imation aa0 SABuonrdtvyaimvoNaerlltoenntsObservations 2a&1 MHFCoeooraommndpoonuBCenoodndtyAunCnWoapen1tisygutrhmostpntiGoanins Test Raters] Residue Analysis ii82 8 CnlaitnoimciaclatPatPhaotlhooglyogy 2a3 concuusions u SIGNATURES 2 REFERENCES PATHOLOGY REPORT u2% COMENTS ON THE OATA a CODESGAC,oeodnbAeersBre.BavRlifEaoVtrCIioAodATnenIssaOtNoSaamn,niddcAaUANlnDiotFUsaNbtIlhfTraooSttreotsoCvynlsinical Chentstry 33u%2 L1ESumary of Antesortes Observations 38 542 MMeMoeeaaaannnn CBBFoooomndddpyyoukCWneoedtniosgnuhCemtospntscuiaamoinpnndtiSs(oat3n)dandS(atmraydndsaDereadvisDa)etviioantsio(ngs) (g/vk) ai"a 6 18075 Summary SSSSuuuummmmmmmaaaarrrryyyy of ooooffff Clinical ACCCblllsiiionnniiilcccuaaatll]e Chemistry Data - Week OCCCrnhhgeeeammmniiisssNttterrrlyyyanbbDtaaatttahaDat--a'NWee(eee3kk)k 82148 Week Sacrifice 56 &5si@7 1311 12 Sumary Summary Summary of Avsclute of Absolute of Absolute Orgun Organ Organ Veioht Weight Weight DutaData Data (3)(g) (g) - - 8 Week Sacrifice 2164 WWeeeekk SSaaccrriiffiiccee &62 64 5 - 01774 HI 6329-100 CONTENTS. (Continued) OLE | OF II(Continued) TA14B"LE(SCumomnatryinouefd)Organ-to-Body 15 Summary of Organ-to-Body WWeeiigghhtt PPeerrcceennttaaggeess-- 8 WWeeeekk SSaaccrriiffiiccee 1176 18 SSuummmaarryy Sumary ooff of oOrrggaann--ttoo--BBooddyy Weeiigghhtt PPeerrcceennttaaggeess Organ-to-Brain Weight Ratios - 5 -- 2124 Week WWeeeekk SSaaccrriiffiiccee Sacrifice 2108 21 SSuummmaarryy Summary ooff of OOrrggaann--ttoo--BBrraaiinn Organ-to-Brain WWeeiigghhtt Weight RRaattiiooss Ratios -- 814 WWeeeekkSSaaccrriiffiiccee 22 Week Sacrifice 2223 24 IInncciiddeennccee Incidence ooff of MMaaccrroossccooppiicc Macroscopic OObbsseerrvvaattiioonnss Observations -- 814WWWeeeeeekkkSSSaaacccrrriiifffiiiccceee 2265 27 IInncciiddeennccee Incidence ooff of MMMiaicccrrrooossscccooopppiiiccc OObbsseerrvvaattiioonnss Observations -- 22WeWeekekSSacarcirfiifciece 8 Week Sacrifice 2298 30 IInncciiddeennccee Incidence ooff of MMiiccrroossccooppiicc Severity of OObbsseerrvvaattiioonnss -- 2124 WWeeeekk SSaaccrriiffiiccee Microscopic Observations- Week Sacrifice 3312 33 IInncciiddeennccee Incidence ooff of SSeevveerriittyy Severity ooff of MMiiccrroossccooppiicc Microscopic OOObbbssseeerrrvvvaaatttiiiooonnnsss -- 814WeWeekekSSaaccrriiffiiccee 22 Week Sacrifice 3345 36 SSuummmmaarryy Results ooff of HTeosrtmonMeateDraitaal Residue Method Validation for ADneatleyrsaifsnation of T-5180 in 37 ResRuoldtesntofFooSdtabEixlpirteysseAdnalayssitshe Percent of Recovery 3398 RReessuullttss ooff DHoosmeogePnreeiptayratAinoanlysAinsalysts APPENPDrIoXtoAco] Deviations PPrroottooccooll ATnPeSn32d]nent No. | PPrroottooccool] AAmneennddmneenntt NNoo.. 23 Material Safety Data Sheet APPENDIIndXiv8idual Antemorten Observations IInnddiivviidduuaall BFoodoyd WCoenisguhmtpsti(ogn) (3/vk) APPENDIIndXivCidual Clinical Chemistry Values Page [0] "7 b7i83 88 8a 5a0 99% 110025 111018 111174 112220 123 112268 130 113332 i134 115502 154 115538 1m 139 222212 10 Co1775 CONTENTS (Continued) VOL11UOMF1E1 APPENDIIndXivD.idual Absolute Organ eight Data (5) IInnddiivviidduuaall OOrrggaann--ttoo--BBroadiynWeWiegihgtht PReartcieonstages Individual Animal Pathology Data APPENQDuIaXlity Assurance Statement Individual Hormone Analysis Data APPENRDeIsXulFts of Individual Test Material Residue Analyses APPENMDeItXhoGd Validation for FC-143 fn Feed Method Validation for T-5180 in Rat Serun HHI 6323-100 Page 223332 254 221555 662210 622 663209 46445 651 n - CO1776 HW 6325-100 ABSTRACT AeTvmhaemlounpauitruepmosrPeeesvrefrolsfuiobrtiohloicisttaysntoouafdtyea,wnayswhteotxnoicafesdseefsftseocttrshatesasftfueobrrchraatopnpirlceoaxsittmoaxti1ec3litywy8eekosfwee1akn-sd518wt0io,thout t0(r5e5(a/ntgonrneopnautip.r-ifneTdGhreorcuoepntswreor1le)t,h3r2o01,ugmha1l0e,5,'3C04r,5l/:gC1r0O0oO,uBpRorriant0sGrpopaumspsi(gc6)nonetdarnodalt fegrdraonuddpioemtpsatiorc-osfnietxdaignrtioonugptshe aG8rroowuueppesksfe1dpotsh1tr0t0oruegphapt)e5ntf(.odresiupgnafoted13asweerkesc.overIyn aandidmiatliso)n,we1r0eafneidmablass/aslex/dgiertoupforin TbFhoeeofdoraenciomniasnluismtpitawiteoirnoenwoaobsfsertrvreeecdaotrmdaetendtl,weeawesetkelkytlwyifcoerthedaarnieilamyfa.tlesr,gBiovdaeynndweo1,inght1th0,se dwoearrye30ofrpencpeocrrdaonedpdsyofonrce pwtaehieerk-lnfyoendpfaoirgrro-aulflpesdgrc(ooaunntpirsnoalldsugrrigoniugvpe.nrec0oFvooerordy1.c0o0nspupmm)p.tionFowodascornescuomrdpetdiondaiwlasy rfoercortdheed aT1nh0dera8eniwwneeaerlkess/g1wr5iotuahpnoiumitanlstGrr/eogaurtpomsuepn1ts.tahcrroHiuefgpihacteid5cwaefCrtoeerOsx4a,icdrai7s,feicoeradct13iavfiwtteeyerksw1a3sofwedeetktrseeramtoimfneentdtr;eaftomrent Five animals/group at each scheduled sacrifice. NdSuoernrifunangstseatdmrpelaretasatesnftwreornaend10afnareonsmtthmeatlisaz/neigdmraowluispt/hgwreomrueepthcodoxulylreficnltguerdarneecaotvaenerdaychblfoosorcdhehwdoaurslmeondceolslaaencacrltiyefsdiicsef.rom t(hteotadle)sceannddinlgutevienniazicnagva.hormTohneesse, saanmdplefsorwetresetamnaatleyrzieadl fcoornteesnttr.adiol, testosterane raOlenlleatoaentdihmearelffaegnciitvmseanlson10sa0unrtvpeipnvmeodwratsetomsosabccshreeirdfvuiaclteeiddondssua.rcirnigfBiocdWeye.ekweiTghhedtrueeawntdeorecsuemnvuoelraetteisntveeckmabtosedoryrieasi;- wtehiosgehtofgaitnhefonronptaheir-1f0e0d-ppcomntarnoilmalgsrouwperethcroonugshiosuttenttlryeatsmiegnnti.ficantly lower than gcArnooinunspaulmspattifoeWndeekb1se0t0w1epeapnnmd tch2o.enspunaOeivdrer-afsleildg,'nainftdihceranenotnlwpyaasirl-enfosesdsifggoronodiufpitsch.aannt tdheiffneornepanicre-fiendmecaonntrfoolod CD1oi00AetopaxorimydaaastdemWienaeickststivria5,ttyio8,nthaaotnfdwtah14se. tsetAsatntiimsmaatltiescrailgalilyvenrsiegs1nu0ilftpiepcdmanhitandahttirgdhaoensrseiehneltpealvtyeilcshigpohafelrm.3i0.toyalnd Nwheeerepekathi5.cighpeTashltemitamoteya]nWeeeCknozny8.moexiNdaoacsteidviifatfcieterisevnictfeyortinhaanthiempwaaaltssicgsitvpaeatniinsit1t0io,cya]l30l,yCokosriogxn1i0i0dfaiscpeapntactaitvity wdaisetasreyenaadtminMiesetkra22t;ionthaotf reversible. tihse aftetsetr m8atweereikasl.recTohveeryefffeocltlowwiansg dotshee-d1e3pewnedeeknst oafnd 12 - COLT? HHI 6325-100 Ae1d0i0mgihnptpismstraaafntdteirohneaptaotfoTceteahesltlut4le,satr7,mhaytpaeenrdritar1lo3pwhceyaeuksisendtohfienctrrleeiaavtsemeredsntao.fbsaoTnlhiuemtaelpsraongdgirveresensliaot1ni0,veof30l,iveorr htireneptaarttamoceceneltll.luullaarTrhemehtcyahpbaeonrglteirssoaphoyabnsdedrimvdaeydnotabereaapsspesuaogrcgieasttoteidvbeewioatffhfeapcettreedostxibsmyaotmteehreiparlolelniegfftefhreacottfioonn. At ttrheheveeretsenisdbtlomefa.treercioavle-rrye,lattheedse icnhcarneagseessweirneanbostoloutbeseravneddreinlaatniivmeal1si,verinwdeiicgahttisngwetrheat Tahhotertmrroeinbeuwtaesldevneotlosctowhneesriestteessntitgmnaiptfaeitrctiaeanrltnlyofvoderriftftheheerehneotnrtmiobrneeetwecdeoenutresgrermoiunopafstitoahnelsthsowtuhugdiyhc.htcheNorouenledaobpfepeatrheed dteotebremisnoamteioinn.dication of elevated estradiol for the 100 ppm group at the Week B1Tea-vs5ee1l8d0o1n5whet1nh.e0ferpdeps.u2ldtsTiobfituthsisto struadtys, fotrheatnol-eoabsster1v3abwleee-kasdveisrse1-0e0ffpepcm;t tlheevelno-feofrfect 13 Co1778 HI 6329-100 OBJECTIVE AThmeonp{uurapoPseesrfloufortohoicstasntouadtyewa(sCAStoNoa.sse38s2s5-t2h6-1s)ubcwhhreonnifcedtotxoicriattys offorT-a5t18l0e,ast 813weweekesk.s and to evaluate reversibility of any toxic effects after approximately REGULATORY COMPLIANCE HAalzleatsopnectWsashoifngtthoins s(tHuWAd)y wtehraet winereacccaorrrdiaendceowuitthbythHeazElentvoinronWmiesnctoanlsinPro(tHeIc)tioannd Agency Good Laboratory Practice Standards, 40 CFR 160. MAINTENANCE OF RAW DATA, RECORDS, AND SPECIMENS Oilrliginbael rpeatpaeirneddatian, thmeaganrecthiicvaelslyofenHcUoId.ed Srepceocridmse,nsawnidlla bceopytroafnsftheerrefdinatlo rtheeport Sponsor and are to be retained in accordance with 40 CFR 160.195. TEST MATERIAL IdentiafndiChcaraactteriizaotinon NToh.e and t1e15s,t miastearilailg,ht Tc-o5l18o0r,edApmoowndieur.m PeItrfwlausorroeoccetiavneodateat (HCWAIS was assigned HI Sample No. 0058Al. No. 3825-26-1), Lot on November 7, 1990, dIenffionrematthieonteosntsmyanttehreisails mfesthoondsf,ilecomwpiotshittihoen,Spoonrsoort.her characteristics that StorageConditions The test materfal was stored at room temperature. ReserveSamples Rseasmeprlvees swaemrpelersetuorfnetdhetotetshtemaStpeornisaolr accordance with 40 CFR 160.195. Any woenreDecteaskbeenran1d8, st19o9r1edtoinbae frreeteazienre,d remaining test material was returned iTnhese to the Sponsor on December 18, 1991. SafetyPrecautions DpaetrasonSnheelet i(nMvSoDlSv)edpwriotvhidetdhebysttuhdey covered by the MSDS. Swpoornesotrh.e aHpMpIareSlOPsreaqpupilrefded bfyortheanyMataeprpiaarlel Sanfetet 1" - CoL779 HMI 6329-100 TEST SYSTEM TestAnimal aRHnaiilvmeearlCsrL1aw:beCorrDeatBoRarpiprerasto,sxiwmIeanrtc.eely(oWb4it1lamiindneagdytsofnor,iodmMaattshseaicnPhoiurtstieaatgtteis,o)n,MoifocnhitgDraeenac,temmebfneatrcial7,nidty1w9e9o0if.ghCehdaTrhlees 180.7 to 229.1 9. Trhoedenrtat spiesciferse.queMnatlley ruastesd wienresaufseetdy material on testicular physiology. teovaclhuaartaicotnersitzuedietsheaesffaecrtespreofsentthaetitveestof a Identification ttEaragec.ahtmaeAnlniltm,aldaetwaaacshfoaanrsismiaagnlneandwiamsaalatseasmripegonreardreycoarndpueemdrbmearunneduneptrononnuaemrbrieovrfalat.hnedseBiednfeuonmrtbeiefriisen.ditwiiatthionanofear aAcnciomradlisngwerteo STUDY DESIGN tJhseianfeoldlotwoingthdeessitgund:y using a computer-generated randomization Group Dose Level --foom) 21 0 1 43 3100 65 100[4 Number of --Hales 55 855 55 5[35 3 va1an0simaadnliissm)caolnswteirfneouretdrGerao(tuaepndsimaf1losrthwaretorueglheafse5td (t1dh3eeswibegaenskaastl,eddtihaeestn)rtearcneodavtemrteyhnety oecrceurroebnsceerveodf tfooxricreevfefrescitbsiliftoyr, atperlseiasstten8cew,eekosr delayed b Aapnnoiismmtaatllrsseati(mnGernoGtur.poup5) 6twhreorueghpoauitr-fterdeatwmietnht.theDuheigtho-dotshee pairg(frGeoreuodpuispn.g6)reqwuerieremiennittsi,atetdheonpaitre-stfedonecondtaryolaftaenrimaallls other 15 - O1780 INI 6329-100 dSIetnvaditiaviitsdituoianclsallobyfodydCihwfeefiemgreheatnnstboaatdtytthhweeeigthi5t.m0e%anopdfrogbrraaobnuidploimtsiyeziantlievooendlywe(reNei1new3ri.t0hi1nv9e71r2)s. snottandard PROCEDURES T19h5i0s, stanuddyAwnaesndnceonntducNotse.d i1ntahrcocuogrhdan3.ce wTihtehprHWoItocPorlo,tocporlotoTcPoS]321andeandtneedntNso.vempbroetroc3c0], dpoerrvoicbaeottdhiu.orness, `waenrde dMoSnDeS ianreacincoArpdpaenncdeixwitA.h tUhneleasbsoveo-trheerfweirseenceidndidcoactuemde,ntsa,ll HI SOPs, DoPsreeparation Carrier. Certified Rodent Chowe #5002 was used as supplied. TeSusptpMTiaetde.riaDli.etsDwieertearyprcepoanrceedntrweaetkiloyn.s were based on the test material as Ambalirexsinipdnneeggcri;bfbloiweetlnhdedeafrmrrooeumaqnnutwdihrieoocdfvhercalmaaaopriuprdnritoewxriiotfm(habttaeesasalptlyprmod2axi0tei0etmr)agitaewwllaeysrweaw$s0reeitgmghoheovenfeddwciaeanrintcgdoiheepardl,alcaaentbddheelneaiddndteHhadooWrbaoaSruorigtnhTglyye bmliexnidnegd;boutlhiwserperemmiixxedwasfortraapnpsfreorxriemdatetloyth15e smiinxuitnegsbotwol.prepTahreectohnetenbtasseofdietth.e dDaaiidpeedptetrdsoxnitwtmoeoartetehalemyaldmaeib1xe5ilfnemogidrnuHbGtoorewboslua..prstT2,hmeix3,icnogn4,tebnoawtnlsd. o5fAbythseppelmcaiicxfiiinneggdaabomsuopluenctwiefrioesfdbmiaaxsmeeodundtifeotrofwebsasal Bameoguinntninogf amount of abtthaesWaeGerkdoiuep3t, 3wtadhsieetmpilwxaaicsnegd apdidrneotdocedatourleathbeefloemrdixGirHnoogubpabro2twlw.aBsiximTnongdeifbciooewndlt.enatnsAd +spsepciefciiefdied of tne mixing bowl were mixed for approximately 30 minutes. T(hHeeedksiet3stwherroeughsto1r4)edinatcornotoainteermsperuanttiulredi(eWteekasdmi1nithsrtoruagihon8,) or in a refrigerator Retention Samples Spaomspsliebsleoffuteuarceh mainxaelydsibsa.tch were stored in a freezer for at least 6 months for 1 91781 1 6325-100 DoseAnalyses Assays for the test material in the basal diet were done by HNI using an analytical method developed and validated by HNI (Appendix G). Homogeneity as geternines for 41) concentrations at ek 1. pomsgeneity was also dttheeesttertmmopai,tneerdbioatfltoormc,otnhteaenndlto.twu-odosoeppo(1sinppgm)sicdeosnceonftrtahetiomnix awterWeeekass2.ayedSamIpnleduspltakaetne frfoorm asTonaamlpeylvzeaeslduawteoernetthhteeakdesantyafborifolnimtiyexaiconhfg,tdhooesneetepssrteetpamwraaatsetriioaannlalmyiizxneeddtheaffotbraeseraelsktodri1.ietg,eOnffeoorurseitsdewatayssionf a refrigerator and 7 days at ron tesperature; and the remaining sets were analyzed after being stored in a freezer for 2 or 7 weeks. Adursiencgondthestafbiirsltityeigwhats wdeoenkesatofMetehek s12tudtyo. evTawlouatseetstheofacstaumapllesstwoerraegetackoennditFiroonns each dose preparation; set was analyzed after one set storage was analyzed on the at room temperature day for of mixing 8 days. and the second sAsIea1lmepcldteieedotsfstweheqerueencotanistasrlaolylyeddfioeeratcahnaaneldeyksoinsef.otreTsththeesmeaFtiersrsuitmall4esdwieveeektsra.sryanEcaaolcnyhczeenwdtereakatsito3hnegrweraaofustper, 3 approximately every 4 weeks. All samples were stored in a freezer until analyzed. DoAsdeministration Dietary adnixture was used to compare data with other studies dosed in a siaflar fashion. eT1x3hecewpetteeksstthmeoaftpeatririrea-altfmeedwnatsc,onatd1r0aoilmnaiglsertsoeurpe(dd(eaGsdriogunIpaitb6ei)dt,uanswefrorerecafotevderlyebaassaatnlim1a3dliswe)etekffsor.romatAalfltleergsrsoups, 8 weeks posttreatment. Acclimtion The aniaals were received on Decesber 7, 1990, and were acclimated in Anim] Ranoiommal3s15wefroer o13bsedravyesdbedfaofrley ifonritiaabtnioornmaloiftiterseatimnednitc.ativDeurionfgheasc)cltihmaptrioopn,emtshe 7 - 01782 WI 6325-100 HouandsMaiintnenangce . Ar5no0io%nma]7v0e%rR,eoosamentd315taow1am2sa-ihnoutusareidn1ifgoarhtt/te1hmi2ps-ehroastutururdyed.arokfEn7cyv2cilrFeo.n3m6e,natraailartceiolonanttsriovlefsrohnufmoirtdhitethsye oafnimal coountdciotmieonosf wteherestduodcyu.mented and were considered to have had no effect on the The animals were housed individually (except for the first week of acclimation) in sscinhteialpiethnceltbeeeGdsdudsiiandsnge.tiemfeaollr,sAtniwhsmecearrleeCeahniru-nesbdboiaavtnnitdddorUumyaslcelaagynoedfshL.ohauobsuesoWdihrneagnitnoaartnpyioAmHlaNnylIciamrhcabeoloamsnlpatlthy(eNwIsiHcttaahgtPeuusbsslt:wwaainrdtNroah.arndhts8ae6rd-do,2wu3to,)odined 1385) CnTueotrtrtiintfuiimoebndearlsRodaceronemtporneCechonortwdseda1.n5d002Tehnev(iPrduoirneimtneanftWsaillrloscu,otnitnIaenmlci.yn)aanwntaassl.ysperdovibdyedtheadma1niubfitaucst.urerThefor Wdaitsesrolvweads elements, pshoerlaoivvdyisd,eBdethaaalrdsd,n1ebsoisrt,guasna.ondphoSssappmehpcalitefesise,dofmaintcdhreocbwhilaootlreoirgniaactraeeld ahcnyoadnlrtyoezcneatdrbbaoynndsW.fIorTfhosereletcottaeld results are on file with I. wTihtehrethwiesrestnuodyk.nown contaminants in the food or water that would have interfered Antenorten Observations CTaahngedeasinagnidnmsalasodfewtetaroeixliecoidbtsyee.rxvaemdAitnattwTiieocanestdwaaosincleydonw(eea.e8k,ly,andeacph.m.a)nimfaolr mwaosrtarleimtoyv,edmofrriobnunfdiisty, Body Meiahts ttIhrnaedtaitvmwieedrnueta',l nwobteoedkywleywiegihtgehhdetrebaedffaottreaer',weerxaesnadnrgoeuncionrtadhteedidonaf)yo.rofranndeocmriozpastyio(ne,xceopnt tfhoer ftiwrostandiamyalosf EoCuodnsumption fIenddiv(iGdruoaulps foodandco6n)sumapndtiowneekdlayta fworere211recoothredredandiamiallys fdorurianngimatlrseattmheantt.wereDurpianigr- recovery, food consumption was recorded weekly for all animals. 1 - C01783 INT 6325-100 tornone Analysis dacSaunevreraisuntmghaensdttairmzepsealtdteomsrewenidwttehorneamnedcitochlefolrxeouycnmfttileludraacnfneirenmo,tamrlisa1fn/0udggraaobntuliipomooanddl.uswr/aigsnSrgeorucupromelclaoetsvcaetmerepaydlc.ehsfsrwoNcemohrneefdtahueslsteteddodreessdcraeacntradsitifniwgceerevena vaaneparpliryfosixieisd.m)'a,telStyheernu-n7p0asacCmkpe(ldeexsocnewpetdrreystoairnceaa,gieyzaenlddocafsothriiopnepsetdfroartdoi3oHlecozllaneedtcotntieosNntaosshdtiaentrgeoisnoencanf(ntooorttalb)e and Tutelnizing hormones. Test Materia) Residue Analysis Sfarmopmleasll ofanilmivaelrs,'sttesnteecsr,opslyungasn,d asntdoresdubfcruotzaenneoufsorapdoipsossiebletisasnuaelyswiesr:e cSoellrevcsted residue. starmepaltemsentcolanldectferdom fr5 omaniump altso/g1r0 ouapnimdaulrsin/ggroruepcovateryeacwhereschaendaullyezedd safcorritfeiscte during material Clintcal Pathology A section of flash frozen liver was in 1iquid obtained from all animals at each scheduled sacrifice nitrogen. A section of liver from animals/group at and each scheduled indicator sacrifice was of peroxisome assayed for the proliferation. level of palmitoyl CoA oxidase as an Anatonica) Patholoay AAm1ef0tt:nh0ee0orcxryao4f.,pmls.uy7r,aw(naoeesrx,ced1wpo3etniegwfheooeerndk,stthhreoeexfesaantniramgenauailimtnamalettsnhetad,tt,hwanataosnndfwaessrnateececrdnrieofcpiarscnoieipedmsdailiesbndewtaewaremfeeotnreirab7nu:e1n0s0d0t:0h0cea).ot.mni.dzietdRaineodwcnio.tvhery animals were sacrificed after 8 weeks without treatment. The necropsy included a macroscopic examination of the external surface of the bsopdiyn;al alclordo;riftihceesn;asatlhecacvriantiyalandcavpiatrya;nastahle esxitneursneasl; sanudrfatcheestohafratchiec.brasibndomainedal, and pelvic cavities and viscera. Aptairtehde osrcghaendsulewderenecwreoipgshye,d tsheeparfaotlelloyw:ing organs (hen present) were weighed; BLriavienr Lungs ATcecspertosessstoar(tyoen,esextceosaotgriugsla)nastin(gsegmilnaanld, veusriectlher,a) 19 M C01784 HHI 6329-100 Organ-to-body weight percentages and organ-to-brain weight ratios were calculated. Tshcehedfuolleldowisnagcri(fwihceen apnriemsaelnst) anodr unless otherwise specified: prreepsreersveendtatiinve10sampphloessphawteree-bcuoflfleercetdedforfmraolmin, BrLeasiinons LiLuvnegrs ATcecsetsessor(yonseextesotrigsa)ns (seminal vesicle, prostate, coagulating gland, urethra) Thheemataobxoyvelin(asandappeorsoipnr,iataen)d weexraemineemdbedmdiecdrosicnoppiacraaflfliyn,frosmectaliloneadn,imasltsainferdomwwihtihch they were collected. Agtluttaheralsdcehheyddueledfornepcorsospisbylesameplleecstroonf mtihcerofsoclolpoiwcingevatliusastuieosn:were preserved in LBirvaeinr Lungs. ATcecsetsessor(yonesextesotrigsa)ns (seminal vesicle, prostate) StatisticalAnalyses Twhaes dsotnaetisttoictaelst meftohrodvsariuasnecde arheomdogeesnceriitbye.d beIlnowt.he Lcaesveeneo'fshteetsetrog(eLneevientey, of1960) varfance at p < 0.05, transformations were used to stabilize the variance. Atnraalnyssfiosrmeodf Kraner test vdaatrai.anceIf [tAhNeOVAANO(VWAinewra,s s19i7g1n)i]ficwaanst,donGeameosn the and (Games and Howell, 1976) was used for pairwise HhoawmeolglenMsoaduisfioerd Tukeycomparisons between groups. Opcnoeenl-swutanyptpiAeorNncO,eVnAtcalwgaiesnsi,cuasleadndcohteormgiaasnntarltyyo,z-ebhrboaroimdnoynewweeiivggahhlttuse,sr,atciouormsgu.alnatwiBevoiedgyhbtwosed,iyghwotersig.gahnt-'tcgoua-mibntosdi,yvefood b(oedxycewpteigGhrtoupgain)s,usi`anngd fthoeodSAcSonpsruomgprtaiomnavcaclouredsingwerteo aHNnIalymzeetdhodfso.r ali groups Group comparisons were evaluated at the 5.0% two-tailed probability level. RESULTS Grrouop w2s5., 3, 4, and 5 were compared with Group 1; Group 6 was compared with 20 - C01785 HI 6329-100 DoseAnalyses Rsetsaublitlsityofantdesttodiveetrifayssadyosse tolevceolnsfirfomrmTet-h5o1d80vaalriedaitnioTna,blehsomo3g6entehirtoyu,gha3n9d. rMaentgheodofvadliiedtaatiroyncornecseunlttsratiinodnicaitnedthethasttudtyh.e method developed vas suitable for the poMferaondtuhceheodtmhoeagoernheeotimitocygaelnreeoslueusvletlsdsi;sftortrihbedusiteeitosrnescouolfnttsTa-i5ni1in8nd0gicai3tn0edtphpemthdaatinedtth1ae0t0mtiphxpeimsnegwerlpeervoecwleisdt.uhrienMe1a0n% ahnodmog1e8n%eiotfythreesutlhtesoreftoircadlietvasluceosn,tairneisnpgect1ivpeplmy.and 10 ppm T-5180 were within 19% JAlolwertevsatludeisetsofwetrhee 1,8ay, than at room ctteohmnepsoeriredtaeitrcueardle s7t(a1db.aely.es,,u7n7d85e%r%ffotorhrethtsheteorsasagamempplleceonsdtsiottroierodendsraetfsrpiergcoeiofrmiaetde.d The atneamlpyesriast)ureweredacyosn,sisatnednt77w%itfhorthtehevsaarmfpalbeilisttyoreodf tfhreozeanssafyorat2 twheeeks1 pbpemforleevel. Dc70oo.sn0ec%e-np1tr1re9ap%ta,iroant9si0o.n1w%e-ra1en1a6al%cy,hsiise8v7er.de0s-ud1lu1tr6si%ngianntddhiec9a0tse.td1ud%y-t.1h1a1t%Thtehoefastahspeapyrotprhereoisruaelttteiscdairleatndgaoersdye frleovmels of 1, 10, 30, and 100 ppm. Acclimation tfIhoairbsortahstihosirpymsetnuatdnyi,maaplp3e7av0reemtdaelreihsneaalrwtieharyne. ronecTeDhieevceeadmnbiemaranlds17a,wceclr1ie9m90ar.teelde.OanseedIannfirgmoeamnleraawclac,slimeaaxnctilimuoadnlesdbyinftrhoem 4rs5ta/ungddryoomuicpzoantsfiioordneGrrafotouripona6s)sd.iugenmAtenonitmsamlatslol gnorttoeusptsesesl.e(c5t5eT/dhgerrofeuoprwetfrhoeer G36r9oupmsale1,s 2i,n t3,he4, and 5; study were sacrificed and discarded on December 21, 1990. Survival AO1n1e oatnhimearl agniimvaelns 1s00urpvipvmedwasuntsialcrisfcihceedduleddurisnagcriWfeiecke.4 due to severe neck sores. AntenortenObservations AApnpteenmdoirxtem8. observations are summarized in Table 1; individual data are fn There were no test material-related antenorten observations. 2 - CC1786 HI 6329-100 BodyWeights Body weight data are sumarized in Table 2; individual data are in Appendix 8. Bclooondwtyerrowltehiaggnhrtosutphefo(nrGornotpuhapeir61)-0f0e-adtppmcsotnuatdnryiomlailnsgirtowiueaprteio(nGsrioagunnpdifwi1)ecraetnhtrlcoyoungslhiooswuteterntttrlheyaantsmiteghnentifpia(cWiaerne-ktfsleyd 1 wt10eh,irgohuotgrsh30n1o3t)p.epdm. DleuvrTeihlnesgr.erweecroevernyo,sitghneirfeicwaenrte bnoodystwaetiigshtticaclhandgiefsferfeonrceasnimianlsbodaiy 1, Mean Body Weight Gains Mean body weight gain data are sumarized in Table 3. MpTeaoaiwnre-rfbeotdhdayncownettihregohltnoggnarpioanuispr-ff(eoGdrrocutophnet6r)1o0l0at-gprpWoneuepkani(1mGaralonsudpwwee1r)reetchsorinogsungiihsfotiuectnatnlttyrleyasthimigegnnhitefric(aWtnehetaklnsyth1 e tcohnrtoruoglh g1r3o).up e(Garnoupbod1)y recovery, there were no wfsteoaritgihastntiimgcaaalilsns gdwiivfeefrneeres1n0icgeonsrif3ii0ncampnetnalnyatbloodWwyeeerwketih2g.ahnt Dtughraeiinnngg.onpnostierd-.fed FCoodnsumption AFpopoedndcioxnsu8.mption data are sumarized in Table 4 ; individual data are in Afdeindfifmeacrloenstnrcfoeelding1r0om0uepapnom(Gfro(ooGdurpocuop1)ns5)uamtpctWoienoesnkusmebde1 twasneidegnn2i.tfhiecOapvneatrilaryl-lfl,eedssthaenfdroeodnwoantsphaainnor-tfhseeidgnngiorfnoipuacpiasrn.-t CompoundConsumption Compound consumption data are sumarized in Table 5. AapnnrioomupanoltrstioofwnearTle51tf8oe0dthdceioentsdsuomseecdonastbayifnotilhlneogwasn1:,ina1l0s, 3o0n,'aomra/1k0g0 opfpmboodfytwheeigthets/tdamyatebraisails.wasThe O0verall Mean --EC(.--oo--nDaiceT/ t5eQ1o8kn0 a tr/3ad0(otpamiyo)0n [0X.3086] 00.16348 01l.49048 6j.i50) 2 - o17s7 WI 6329-100 HormoneAnalysis AHpoprennodniexanE.alysTihseredatwaerearenossutmaatriiszteidcalilnyTasbilgenif3i4;canitnddiivifdfuearlencdeastabaerteeeinn groups. Tahtetrreibuwatsednotocothnesistteesnttmaptaetrtiearln ofvoerrthteheheonrtmiornee dcoeutresreminoaftitohensstwuhdiyc.h coNuolnde obfe the hdteootrembreomniesnoanlteeivoeinln.sdiwcearteionsiogfnifeilecvaantteldy deisftfreadrieonlt fbeotrwetehne g1r0o0uppspmaglrthoouupghat ththeereWaeepkpeared TestMateria)Residue Analysis RddeaisteuatlatrasyreoefxipnotseAsuptrpeenmdacitoexnrcieFa.nltraSsteeirrouunnm albuentvaellytsshiesorfeaTrwae-s51s8nuo0maiirnnicczrreeedaasseeidnfTpnarboslpeeorrutm35i;oTn-a$il1nl6dy0iviwodivuteahrl the course of exposure. Clinical Patholoay Hepatic Palmitoy] CoA Oxidase data are summarized in Tables through 9; diinsdciuvisdsuiaoln dofatathearedatian. Appendix C. The Pathology Report contains a complete Dpgsaiitlveanettinaitrsoyt1y0i]capadolCmlnoiyAnhiasosgtxiigrdntaairtsfaiienocsnaianeoctnft.tilvtyihteTyhhetieagstehtfefrdemocashtteeeprwaliateasivlce,ldsopsaTei-om5-fi1d8te30op0,ye'lnandcdeCanoutks1e0d0oaxnidhpdpiamgrsheeevtrehraasthcietbwpilaavesti.itcy Athnaitmals waansimasltsatgiisvteincal1l0,y 3s0i,gniofric1a0n0tppamt eweerke 5higohnelys.t atTheWeemkean8.enzyme activities for Anatonica) patholooy Organ weights, organ-to-body weight percentages, and organ-to-brain weight ratios asoThrbueesmemrasPvruaaimttzmhieaoodrlnioszgieyndaTrReaeipbnolireTnts.abTla2ceb2oslnettsah1ir0no3s0utghhrtaohur2c9goo;humgphl2i1en;t3c3ei;mddaeicn41src1coeusscoisofnipdoiiscnveivdoeaufrnadilttymheidcaortfdaaotsmacia.rocepr.iocsicnofpAiipncpdeinngdsixar0.e Aradefmltiaentriivsaettrallteiiavsoetnr ow4,efigt7,hhtesantdeasntd13mhawetepeearktisoacleo,flluTtl-ra5e1ar8t0mh,eynptce.arutsroeApdbhsyoilnuictnreeatshleeidve1riavbewsreosilguhtotefsaannandigmals rpseauligargt-eifsvetedivecloinvotefrroalwsetiegsathfttsemartfeo4r,riaa7l,nimaeanfldfsec1tf3eowdnee1k0is0ntoprfpamctewrleelarutelnaersnitmg.entiafTbihocelanictshlmayn3ghdeisgnhaeoyrbsetbrehvaendthaere z 01783 HHT 6329-100 oTabessasesotrcvie8adtweedienkwsia,tnhimiapnledsriocxatithasitonmgewetrhpaertoltitrfheeeartaettdeisotfno.mratateDruirliaenlags-trerle1a3ctoewvdeereykc,shanatgnhedesseuwnectrhreaenagtreeesdverwfseoirrbelaetn.ot CONCLUSIONS BTa-s5e1d80onwhetnheferdesualdtsliobfitutmhisto struadtys, level is 1.0 ppm. fotrhe atnol-eoabssterv13abwleee-kasdveirsse100effpepmc;t tlheevelno-feofrfect u 01781 StoATURES WN 6329-100 T52i0dd)e`cD.oorHdainneakteor Toxicology CDiplhomaoteS, uApB ceh:ipbe SDTtoiuxrdieyccottoDoriaryector by and for Hazleton Wisconsin, Inc. _ Bite shokr - . = 01790 I 6325-100 REFERENCES Games. . A., and Howell, J. Unequal N's and/or Variances: F., A "Pairwise Multiple Monte Carlo St Comparison Procedures with Statistics, 1(2):113-125 (1976). udy," Journalof Educational tIhnesCtiatrueteanodfULsaeboorfatLoriy oAnrisialAtnRaeismoraulrysc.esNiClombiisssitoenntioonnLihefte SSeciseancceso./sSGUuide StoErforL of Health and Human Services, Bethesda, Maryland (1985) Public Health Service National Institutes of Health: University Press: Stanford, California. (1960). Levene, H., Probability a"nRdobuSsttatiTsetsitcss,for(edEsq.u)aliIt. yOolfkinVaretianacle.,s,Ch. Co25n,trippb.uti2o7n8s-29t2o, Stanford pVriinnerc,iol8e.s3.,in C"xDoeesriignnenatnadl AnOeasllyasni,s oSfecoSnidnglEde.-,FaCchteor3.Exoppe.rim1e4n0t.s55,0", SRteamtiisitpiccsdl New York, New York (1971). 26 01792 PATHOLOGY REPORT HNL 6329-100 SUMMARY hgDaifcigfteheitecvatirtyhwyaasadtmdiodnsoiess-etdrealpteeivnoednlesnotfofaTn-3d0518rae0nvdecra1su0is0beldpeo.hmigtAhhneairtmawhlaesspagtsiitvcaetnipsatl1mi0ictapolpyln]yhasCdiogAntiorfxaiincdsaainseten,tlyThe it Merek highest 5ae.tpaWteiTechkepm8a.elamnitoeyn]zymCeoAaocxtiivdiatsieesactfoirvitaynimtahlast gwiasvenst1a0t,is3t0i,calolry 10s0ignpipfmicwaenrte AJldeamavsietnrisw4,teriagth7,itosanndanodf13 htwehepeeakttsoescteoflmlatutrleeararitamhelyn,pte.ratlrsToohpehcyaucshieandngtehisencolrbiesvaeesrresvdedaofbasroaelniumtsaeulgsgaensdatfitrveeerlatoaiftvea ptdneerstoaxnimisamotamelersiaptlhraotleifffweeercratetitoonrne.aitnetdrInafctoehrleluatlraerlceoamvseettrayb1o3phlawiseseem,ksantdahnedsmeayucnhtbareneagatesessdowceifraoterednatotwiltoehbssserved 8 weeks, indicating that the test material-related changes were reversible. INTRODUCTION mT3a3hteewrepieuakrlsp,osaenTsd-51too8f0tehv(iaAslmuoisnttieuudayrewvPeeerrrsefilbutioolrioatosycsteasonsfoatatnheye),tsouxwbihccehnreofnffieecdctttsoo.xriactFisotuyrfoogrfrotauthpesletosefssttmale SC1rr:o11u:0p,CDwa3sR0, praaoitrsr-1f0(e05d5p/wpgmir.touhp)t"Thwewoerhceiognthfr-eoddlosdeigertgosruopuscpornettchaeriionvuiegdnhgounttohettretesetasttmmeamntatet.reiraiTlae;ln oatne Tceovnetsro)of animals were rAdefevtseeirrgsniaabttieldlietaayss,t rpe1e3crosvwieesretykesnacnoeif,matlorsreatdfmerelonamty,eedacthohecscgeurroruaepnnicmeeaxlcseopftwetrofexoircobteshfeefrevpceatdisr-foffreo.dr controle. at least 8 weeks posttreatment. DoubrsienrgvatMieoenkss pporoerserhveed in wfS$ei,rxea8,tirve1ec4s,ordaaesndd,re22qo,urigraaenndimwabelyisghtthwseerepwreorsteaoccorobiltf.aiicneedOdn,eandaannidnmeatclir,sospsusieaescdr;wiefrimecaecdrodsuceopitco isnedrunfrosazalemtnphlefsodruwreiprnoegssiWcbeoleleklec4at,neadwlyassfiosralhfsooorrmnoetnecsertopasmnaiateledyr.siiasl,Atrteitshsiesduuesec,shaemadnpudlleesdsewcsetaircoernisfciocoleflse,c) tjeeder woefreperoobxtiasionmeed brain, Tver, plfuronorglsia,fsesraTayetfiitnognt.ehsetpiMasit,circoasnpcdaolpmaiictccoeyselsxoarCmyionkasteoxixoinodsragsaewnesraecftprioevmriftyo31r]msesdanainomnailJneog.tieosntee,r Sntoantpiasitri-cfaeld group. ccoonmtpraorlisognrsoupweraendmabdeetwebeentwetehne thhiegh-tdroesaetegdrogurpoupasnd antdhe thpeair-fed control 2 O1793. WWI 6325-100 RESULTS Clinica)Pathology AcIponpmdepinavdriidiuxsaolnCs. vaarlKeue.easninvfTaoalrbulehesespaftoirctherapocauhlgmhidtoos9.ye]grCookupoxainddastehearcetsiuvlittsy oafrestiantistical Mheepact5ik.c paAlnniimtaolys]giCvoeknox1i0d,as3e0, acotriv1i0t0y'pptmhanhadthestnaotnipsatiirc-aFleldy csoingtnrioflicaannitmliylshigher AtInhniacnmraealtssheedg.ipvaeinr-f1e0d0 pcopnmtraollsoanhiamdalsst.atisEtnizycmaellyScstiivgintiyficiannctrleyssehdighaserdoesnezymTeevaecstivity SeAhneeipkmaat8li.sc gpiaAvlnemiinmtaol1ys0] gpioCvnoeknhaodx3i0danaosreap1ap0ca0triepvnpitatlyyhadhthiigsnhteartthiessntzniyocmnaeplalyjarc-tsriievgdintiycfointctharanontllythaenhiionguohrnessr.air-fed cgpoianviterrn-of]e1d00ancoipnmptamrlosal,lsoabuntihmaadtlhses.tdaitEfinfszetyrimeceanlcleaycwtaissviigtnnyiotfiicnsactnratetlaiyssetdhiicga4h5lelrydosesenizgyTnmeievfeilcasacnttii.vnictryoAansitemhsaa,lns sthne tthhean acattivNietcikes5. for animals given 10, 30, or 100 ppm were higher at this interval Mheeepkat1i4c. palAaniitmoaylls Cgoivhenoxi3d0asoer 1a0c0tivpiptmyhatdhansttahteistniocnaplaliyr-fseidgnciofnitcraan)tlyanhiingchyeer 100 ppm were Tower at. this intervil than at Meeks 5 or 8. Animals given 100 than the pair-fed pcopnmtraollsoanhiamdalsst.atiEsntziycmaellyacstiigvniitfyicfaonrtlaynimhailgshegriveennzym3e0 activity or Mbeeetkwe2en2'. theThenroenpwaeirre-fendo dcoinftfreorlencaensd ftorreatheedpatgriocuppea.lmitoy] CoA oxidaseactivity Anatonica]Patholoy yiBInerniadgiTihnavtbislwd,eeusailgah1bt0saonltaruhtatroteomiuoigscoharlgaar2ne1p.awtaelhisoIgolnhoctgiisynd,eAndpcaoeprteganasndau:irmxetaorD-ii.bneosdAyepopafeennidtgWhiheextigm0ha.pcterrocvIseancnldotuipaevigsice.dsuf.aaolnrdaentaageicrchmprironSpsaeelonu-sbooodayre Findings are in Tables 22 through 29. capie SwSacenihiigegmndahiultflssi.ecdvaenSArtaeflctyresirilfgoi4nwc,ieerfsi7.,ctaenortArmlifnyt1ae3lrhwiegb4ehokewdsreyekowfsefoirgothrfatenssittnrmsewe1ahnstetmn,egnictvao,ebmnspoaalrn1uei0td0mealwpsipatmnhdgwihvrneeeennrnapcta1oii0mvr0pe-afprao|egnvderhrveaicdtthral Lts1i0htvoasepnerip-ftioocfa-afbnteoteidlrtyyhe4rhvweieiggeghrkheostrupopifnoefractnerCineomtanaattrlgmoseelsntgwiaevnareniedmnal3iss0in.gtonhpiemfTihceaaansfnitentealr1ly1s4vhegroiirgvhvee7enrgwhe3ite0nskspiphweseofreaanftitraeeeiarsrlgesnenpti.ven y11e39i0gwmhetekasncdhaonfhgiegtshreeraitnmtceelnsuttd.eeds-tATofotwbeeorrdy113iwveweierge-hkttso-pboeafrdcyternweteaaitgageehsntt,p(euorhtcenehnetrcaogmsepisagrneiidfniwcsiaainihtcattasiroguaasnivecnr the nonpair-fed controls) in animals given 100 ppm. 28 01'793 HUI 6329-100 Mbaectrwoesecnopciocnatlrloyl, `atnhdetrreeawteerde afneiwmaolbsseravfatteiron4,s a7,ndorno1m3ajwoereksdifofferternecatemsenitn. incidence TMlhiiivcserrocshcfaornpogiaecaalwnlaiysm,alcshmairgnaiicvnteanelr-it1z0o,e-ds]30ib,yghtoarn hae1cp0c0aetnoptpcumealtalefudtlearcren4h,tyrpi7e,lrotbrourolpah1ry3 wwaeseksobosfervtreedatimnentt.he pattern in which the whaeperppeeaatroraconyuctneed,sed`atgphiepveicanergleldsthtweoerhceaevlelosthaearmwomirosereehpuonmlrouegmmeanreakopaupbselaerc.ayntcoepT.lhaesmEi,xncceaipndtedncfteohreanctdehlelseenvbteoarrrdigeterydsof tohfistrecahtamnegnet in(cTraeblaessed3w0itthhroduogseh,'33b)u.t incidental findings. nAeliltheorthearppeoabrseedrvatotiobnes awfefreectecdonsbiydetrheedlangth Redeaictgoahv.tesr.yMSicarTcohrseicrfoeipcwieec.arlelynAoniaomnadtlhsmeircgrisovisegcnnoipf1iiccpaaplnmltyh,cahdatnhsgeiergseniwfienirceathnetfleywreomhbaisigenhrienvrgataioborsngosalnutanewdeibgnrhoatin mofajotrredatinfefnetrenacneds afitnerinciwdeeenkcse wbietthwoeuetn ctornetartomlenta.nd treated animals after 13 weeks DISCUSSION Doglxigiendtiaafsrieycaaancdttm.iivniitTsyhteraatteifodfnoescetofwlaetsvheeldsotseoesft-de3mpa0etenordriean1lt00acnapdupmseredtvheahrtisgiwhbaelsre.shtepaAatntiiismctailcpsaalllgmyiivteonyl 10Copnpm hs1a6t,dat3it0sr,tainocsraileln1y0t0lyspipghmniigwfheiercreanhtheipgaahtteiscWteepkaatla5.feteokyTlhe8.CmoeAaEnolexveiandtzaiysomene aoacfcttihivevipitatytiietcshatpfaolwrmaisatnoiymlalsCoggiven porxoildiafseeraatcitoinv.ity indicates that the test material causes hepatocellular peroxisome tDrrieeslatatateridyveafodTrniivaentristwleeriaagsthtitosn13 oawffeteetkrhseattanedslteausmntattree4r,aitae7ld, coarus1e3dweaenksinocfreatsreeatimnenatb.solAuntiemaalnsd for at least 8 weeks had no shliievgpenaritfoicsceeaclntltiuolnacsrhahnhgayedpserantirnoapclhciyevnewtrausawteeiodgbhstecsre.vnetdrMiiliconrboutslhcaeotpelidicvaeplralstyt,efrrnommiinntirmweahalit-cethdo-atsnhiiegmhahltesp.atocTyhteesse as3ripmopiuelnaadrredtchetelolcsebentfrmraoolrne tvhheoeimnocgoaenpntpreeooalursedaannitdmoallbsea,cmkoitnrhgee cplyutmopplaasnmd loafrgtehre. affIenctceodmpacerlilsson with intracellular vacuoles. The cell Ibnhooytrphedeervrtilsrdeoenpnwghcetyerh.eoomffTohrateerneyadstdiemesvegteniernnicettryatoaifnvdethtehcehacnecgleellsluslaorrapeapneblanarorergdmeamlteionttibeesdnidoarsensootcriouaantpdepededa.writthoThetirhneecrweaasse aponsismiabllsy isfroiandpiecraotixviesomotef, rperavoneldrisftiehbreialtaiibtosyne.nocreThaoenf Increased storage of metabolic products, o cshiamnigleasr cobhsaenrgveesd inin thtehe rleicvoevreryare increase in intracellularmetabo)isa, dFnidndi1n1gsmaancdrosucnorpeilcateadndtomicirnogsecsotpiiocn oofbsetrhevarttiebsootnths.mawteerArelilacloo.tnshiedreroerdganineciidgehnttalchanges 29 C0179 stauTaes HI 6329-100 ( DipFleZeobG emeartienr ,iryAassraitcsa2tnoogw,c4iosrttsege of (Era eithorogs) Fiinatogs iHst Rar E% (6329-100. 1hm) -- psi o/7-7-- 3 E$e722=2E . ) 01795 HHI 6329-100 COMMENTS ON THE DATA BsYoeamcreaiuosutesablcdeoismfpfue(rteee.nrg.ts, pamrneodagnrcsao,mmspusrttoaeunrnddaprrdoofgdrfeavmoisratwtierorunensc,autseeodrnutimonbdeiarvnsiadludyaizlfefedvraaetlnautelsiy)n, mtahvyiasludeissftfuediryn dssatltaiatgihswttalisycafalrfofmeacntatelhdyosseibsy indtahteoast.eherdiNftefaiebtrlheeensrc,e'stfh.reomintiengdriivtiyduanlorcatlheculiantteedrprdeattaa,tioonr offronthe TrheeferteensctedmataesriFaCl-,143T-5i1n80t,heAdmamtoaniufmorPteersftlumoartoeorcitaalncasteerum(CAaSnalNyo.sis3.825-26-1) is also wdTiahTye1 "asSaltwu"adDyyasyDab1ye,"" 1 bfudotarytfhdoeirffPaelAlrTeHnTitOn.X-TcifToehmepduatPteAarTHTcsOoyXlslteescmytsetadenmdmcatonhnuesailidlney-r1siofrethoendatsaatuddacytoallicenaciptttiiuoarnteion system (e.g., HAZTOX), the study initiation day is "Day 0. The calculation for test material consumption fs: Tot tere) coonestion + a wr RS ee a 0179 WE 6325-100 CODES, ASBREVIATIONS, AD UNITS AbbreviatGCieoondneesrsalaFnodCroUdAnenisattsaonmdfiocrAablCbrhPeiuvmtiihaectlaioognGyshenistry ote: TuihsneefdorfbmoyaltlWioowIningnayS1oimbseet,sneBoeufdtecdomdoetfso,recasebisbssraervrieilpayatrieo1.n1s,, oafndthuinsits are 2 : crave x Mean SD; 5.0. STAND DEV A 8 . ' o HI 6329-100 General Codes and Abbreviations Nusber of measurements in a group. Arithaetic mean. Standard deviation. fGrroounptmheeanmeains osfigntiheficnaonntplayir-dfiefdferceonnttrol group (Group 1) at p 0.05. Gfrroounptmheeanmea1ns osfigtnhiefipcaanitrl-yfeddifcfoenrtreonlt group (Group 6) at p < 0.05. Not applicable; No value. Number fn group. Coefficient of Variance. 3 01738 Abbreviations and Units for Clinical Chemistry Test GUlruecaosneitrogen Creatinine AlTbotuanlinprotein GAllobbuunliinn/globuiln ratio Total bilirubin Direct bilirubin Indirect bilirubin CHhioglhe-sdteenrsoilty lipoprotein cholesterol Low-density lipoprotein cholesterol Triglyceride UArsipcartaactied aminotransferase AAllaknailnieneapmhionsopthraatnassfeerase SBGorarombmmisatuolglplhuatdlaemetyiy]ndroctglreeaannrasasfneecrease CLraecattaitneedekhiyndarsoegenase Amylase Palmitoyl CoA oxidase CIanlocriguamnic phosphorus Sodium CPholtoarsisdieum Magnesium ZSitnrconttun BiTcotaarlbocnaartbeon dioxide Iron TUPonetbraocleunntdirofinrroonnbinbsdianitdnuigrnagcfaocpnaapcaictiyty Plasma cholinesterase Red blood cell cholinesterase Brain cholinesterase Abbreviation (Units) GonLUg(rMGo/O)L) CREAT (MG/DL) AT BPRO(6/(0G0/)OL) A6/LGOBRA(T6I/O01) T BILL (MG/OL) 0 BILI (MG/DL) 1 BILI (MG/DL) CHOHLOL (M(GM/GD/LD)L) LDL (MG/OL) TRIG (MG/DL) AUASI/(SMGGO/TDL)(10/1) AALLKT/SPHGOPST. ((I1U0/7L1)) S6O6TK ((1I0U//0L)) BSP (MG/DL) LOH ((UI/UL/)L) AMYL (10/1) PCOAD (10/6) C1APH(OMSG./D(LH)/0L) NA (MMOL/L) cKL (M(MwOL//tL)) MG (MEQ/L) ISRN ((MMGG//LL oorr PpPPMH)) TBeioc,hes(MM(OwLi/oLL)/L) FE (UG/OL) VTFEIIBB%ECSA((TUUGG//(D03LL))) CHEP (MU/ML) CHER (MU/ML) CHEB (MU/ML) HI 6329-100 u 01799 Abbreviations and Units. for Clinical Chemistry Test ElAelcbturnoipnhoresis AAllpphhaa--21--gglloobbuullifnn GBeatmaagglloobbuulliinn AIdnrseunloicnorticotropic hormone CGolrutciasgooln TrTihfyordoxoitnheyronine ElHecitgrho-pdheonrseistiys. lipoprotein VLeorwy--dTeonws-idteyns1iitpyopr1oitpeoipnrotein Abbreviation (Units: EE AAL]B ((GG//DDLL)) EE AB-E2TA (G(/6D/L0)1) IE NGSUALMIAN ((GU/UD/LM)L) ACCOTRHTIS(OPLG/M(LU)G/ML) G13LUC(ANG6O/NL)(PG/ML) T4 (Ue/oL) EE-LHOLL ((x%)) E-VLOL (%) HY 6329-100 3 - 01500 Code 11-2 Mu NeOxT TAKEN UMNISSUSIITNAGBLE AEUXTCOLLUYDTEIC 8-HIexnnf 0nN Codes for Anatomical Pathology HWI 6329-100 Definition ANIMAL DEATH CODES TIenrtmeirniaml ssaaccrriiffiiccees 1 and 2 SPaocsrtirfeiccoevdermyorsiabcurnidfice #1 MACROSCOPIC CODES OIrngdaincawteesightthantotorgtaakneni;s eexxcplluadneadtiofnrogmivceanlcuilnatnieocnrsopsy Orgnaontesafssing or lost OOrrggaann tauetcohlnyitciacllyanduncsouuiltdablneotfboer wweeiigghheidng Weciaglhctulhaatsiobnesen taken, but will be excluded from all MICROSCOPIC CODES CodesPrefacingNeoolasticFindings PPrriimmaarryy,, mbaelniiggnnannteopnleaospnlasm MLeotcaasltlaytiicnvanseiovpelasnmeoplasm Other neoplasa (see comment) Dist ofFrindi ingb s (nu =St everiityoGran de) NFootcalspecified MDuilftfiufsoecal 3% : 01502 HHI 6329-100 Codes for Anatomical Pathology Code Definition MICROSCOPIC CODES (Continued) GS radees fv or eriort Amouynt 1 2 Minwiiatahl th-ethTeighlteamsitcraossocuonpte of change that can be observed STight - Tess than average asount of change, but readily 3 Moddeirsacteerni- bltehe asavaebrnaogremalamount for a lesion of change that 1s expected ` 5 Mopdoesrsaitbelley Severe - a glsroeesvasetroefam(ofmuuannrtcketdio)ofnc-hoafangmteahrewkieatdfhfeacpmtoreuodnbtacbeloleflscl/ohosarsnggaeonfswith finuvnocltvieosn Toafrgtehearaefafsectoefdthceelolr/goarngans and frequently 37 - 01803 IN 632-100 Table 1 Summary of Antemortem Observations Observation HThuinnched posture HHCriaonlodokeecTdle,ugss,iLoinpnotofusteaidl SSotfitff,Fecteaisl eFRpehiwisntooarrxrihnseoafeces Alopecia SorBHeaesca.kd BlNoeocdky crust Back HReLieagfdhtt fofroerelleegg Neck TaARblidglohntenforepaw ChSSruaoounTiolndetnaincgryorrhea BBLooettfhht hhfiionnrddepappwaaswws Right forepaw HNieTscasriiolntgic, tail TTeiepthof tail -- T T I S xX x G mT 00 00 FE 00 8 oo 21 56 00 2 [o I o o 0 000 oeo 11 o 1 00 00 02 oo 00 0 ooo 11 0 10 0 n[I os 51 sIoon 0 [Io To 1 21i o o 1 o o1o o 0 0 2 1 ooo 00[I 2 1 33 2o0 2 o 1o o11 000 13 oo 0[03 0 1 00 000 0 o 1o o11 o0 10 0 10 oo o 0[0I oI0 000 0 01 o 011 oo00 oo 1 0 0 00 01 0o 01 1 0o 01 1 0o 01 00 a onTuhbimssbeerrvteadbolfweiitnihcnoiduditecnactreeessgartpdheertonanuimtmbhaeelr,sopoferciafnTieicnmgatlnhastuofrfoer,fiwnhseie.cvhetrhieatycc,oonnddriiettvieioronsnibwpiaelsristiys,ted. 38 : 91503 Table 1 Summary of Antemortem Observations WI 6325-100 Observation HTKhuainlncohcecdtuspioosnture HCSriEonVodPk:eTda:gasi,1dpnootfu1se1d1 SFRoehfwitnoorrFrencmoee.as feces RSEoporipesestcaixais BHNaeecackdk B1B0a0cdky crust Head LReifghttfofroerleelgeg ANbRnedichogkhntenforepaw CSshqorutoimneotndiancgryorrhea BLBoeofttthh hhfiionnrddepappeaaswrs TaRfigtht forepaw MNiescTTsriepoiettnhigocf, ttaalil -- 2 ----- -- --S-- TH--(3oL p0m)S1 10080 2 o o0 0 8o o5 o o oo I 331 SE 2 o oz ooo00 o9o0o oo 0 o 111 1 88 nFoE oos s 01 s1 To0o8}6 o 0HI i z i1 oTolo 0 o 0 2 1 ooo o 10 0 2 2 0 1 0 oo 1 i 0 0 1 0 3o e o o o31 0028 0o 1 1 1 o31 08 o Toooo0 r Tooood0 o oo o0 oo o 00 o0T} oo1 80 oo [I 1 oo 0 0 0 oo aoo1 0 1 0 5oo7 3 3 Tanhbuismsebrevrteadobfleuiitnnhcdoiiudcteantcreeessgarptdehretonanuitsmhbaeelr.spoefocriafnTiiecmnaglinshatuofrfoer,tiwnhseie.cvhetrhieaty2c.oonndseie;teieiocnnsninwoianistityi,ed. PF) 01504 WI 6329-100 Table 1 (Continued) Summary of Antemortem Observations * Observation --_-- T5180(opm) I. 0 30 100 2 KSamraltl17mkoevabTleestotnissue mass WTIoenrtriembruiinnnd sssaaacccrrriiifffiiiccceee Recovery sacrifice 1 1 00 0 2 Booo %oo%ok ow 1 3100 00 %o0k oBw1 Rx 0 fom Rumbar of Incidences per anigal, or Tength of ine. the Lond ompers Sted. a This table indicates the number of animals for which a condition was observed without regard to the specific nature, severity, reversibility, " co1saf wre fe ERS OCED ORS BR OBR Ph GOCE HN PROT BLOB OP ion ee ESCH TERR CHER CRA CHE CRECHR CR 0h OBOE B08 Gh POEs Rs Hh RR E30 Rh gs RY 23 2H3 := on Table continued) 32 = Jg 2b few TM WE mms we ws wt we wr wwe me wr we 832 I < 33S .2 $ _ nes nS BB rio ----" Le ePa e EE RR SEEMR EER CERCEOMED COES RR Rn he Rp CEL BS L Bh OSl Wa Wh 01 oe we TERETEERTFRCRHERR RHERRCLCHESBCLHL CR ORG BR Hg BL Ba us a325B a oe STEeI3T(EComBinEs)Choe se -- Te SERS BOBS ORE BS RL ga Ce TERR CHL BORG B39 a 32 -x2 s I SESS LMA 0 SSH ee. | TNL ng mr owl ows mn owe some wr ome me meow 2a g& 5 23B s w2 Te a BE wettt ere Bere be BBB De ECU CRLCHL CEL CORNED GOEL EL gh Boga own Te EER ROHR CHLOE CES CRA EL ORG BR RL oe Se ESHER CR FEDER CRL CRS CG CERO OW RL HS OBL Re CEL BLE RG OEL BORA BLOBS En G0 un. . 3 &* = OR SETAieR4 cEontinLues) oe o--- BR iw Cee ERT HL ED EL us 2 8 8s FL Bb bebe 8H s meme wma wa ma ms ws we wa ows ma we my 23 2a = a 2a2 <a nes WEIR ST on dew FEOROMMONEMotwo momo 0p om ay on og 23 B @@ z a Table (Cont rues) on a 8 <2 2 < i ovo casein tr) BB he hf Be oo + a3 32 w Table 5 wr een 38 @2 - mo o2gFI K woo woo o2. & Ties at an ge 532 - ,os =8 i mG en ve WS EEE of asp apy aR a sh Yan Cen Ten Pam Mew Pw FAI WIZE Pun Due Paw Pu Mae Poe :3-2 , Hl To RE GIG 50. -- Rl 232 82 a2 BS re = Ry RS WEEE Tm fw Yan he of dm HE Mm fw Ye te fw fm a 222 = <a st Ce EE mG gre EEBree HE af Ye fm woPw fm Ve AR fm Ta Pe Vw feefw 222 2 _ El or SpE SRE Cm fw Tae fw Ye Sew HE fwdm ta fm dE fam hilly hglmaohn wRMMR HE Ym Sw Cw Pm Yetw 2S2 2 3 a pe. = el EEE poi - rl oh CEE Tae TwCaCea lam EE eres 232 = @2 digi sasomtronics perce. me. "HEhg oss oo wenn detHanon ui dy HE Sw Me ta Pm fe EE oo TST <-&83 = RE IE pyre. ve BEE iy Bp Sli @B3a e 1 "Hr Bir peesa LS peep HR Ce Cm Cw Cw CwCw SRE Tw Pan fhe Che MRS SE Tm Cw wa Cm Cw Cw o 2 os & Cm HE dm pyre. ve al TE 5i3. ~~ at SAA GIG pen ve LS SRE Ce Cw Cw Cw Cw we 32 , 4 Hl LA Sp HE wm Cw Cw Cw wm Cm 3[ g 2 " HIE mn pane pg ah CerCm Cw Cw ws Uwe SE fm Yn Sw The CB Sen Ah Ce Ces we Cw Cw Cw gE32 x ~~ HE LA SEpe dE Cwm Cw Cw Tw we Cm 32o <2 as i Rg pe Hl SE Cwm Swe Ten Pw Ye AR Ce E Ce ee ww we HE wm CwTw Cm fw 332 = WS we Cw Tem wm 33o & . os al Gg dWaEd|ePC un ReE w PLBmlfUeS Gdahn aPm s HEE Cwm Cw Ce Cw mw hilly HR HE wmCw Tw Cm mm TTT &2o32A. TE RS pe. REBeen La TE pn aki Sam los Tem Tew Yew Mw 38a $2 aE HE rm pare. aif fm Dw tan fefPH w ahh Cw Cw Cen Cw wMww HE Cm Cw Cw Cw Cw Mm HE wm CwCw Um mw 2 8Bo EE SEO SISA ten. ve HEBunn. 3 &2Boz <= Tid! TN By eos ih Bw De tee Pw MCPw HE Ce Ce ww Cw Cw 2 &z &@ Ses LA Sppm ahh Mw Me PenCw fee Mw [33 E.N 2 A HH pe ve -- SWEEE PCwwC Sm PE es Mamm fm 3a 2 ~ HF oo a3B 22 e R/" se ym pe. = PEBgeens we wn psi wo tm 232@ag e Te a TIS EEE Cr EE RRR MR ERS RB Bonu on mg E888 in smn pvc, HEBrg antS on tS n Ereas 2 aB2 os e HE a EE38 dt me srs 3-aBoe Cre wn www CE ste fol 23%2FE EERE EEE RR Bou gen re sp eSATA eV mm i ahh H.32 E AT HE re. ve -- iad -3 2s & Er HE -- win wm vn Ehiidiad B3os a nS EE EOE RRR Egon WSS RE RN oop HE IE pyre. ve pI Sn wy . po aon on ESTE (vs) a3B@ = a TAIRA Toma ait a WOME EB RnB op CEE ROBB on on WME OR BoB ogo on Yama ceo 18 1s us 15 BESal wn on 23b= EER BR Rp og LE had! re 2 2Bs *2 em Co TI EE EE 8 8 EE camara co fa Re R23 e $ WS BB BoB ow og TES TB 8 8ow et ae tu) tear poy 2g2 =:x s82 ELE EE 8B 8: ISS 8 Bow ow sr arse Te a sr wo TILA EEE fo wr ese Re 2gs 2w- pt WM RB R888 $888 REIT SRG pyre. ve Le , mT oonee tn cin aon ms um pele 288 8 * ro RIALSA EE ESE RM Eu og EE EE EE LE RE EEE TT Hate soins peri, ve. > mane [fame 2 Re &8 EE prey Hite totem peste, 1m Ey ota rio oscuro mene Prod a = i Bn pre SES oes mn EE fii R EAp R e Rs l re, FFE nAeEnE wr WATEtsBiRB 8 4 b232.. & HEHs Er } mo mn WEEE BB Rn o Savt 91 CEE OE RB BR 2 coma 1c WEEE OG BR BoB 3 Ene 32.5 & Parsee Ra en pps. ve EL ee wo AIM eins wm sts 81s TE 232 = &8& Hema Svs TR EE CONSE BoB Bon on SE SR Eh z2z2,s & Eo ens eR soon ie on rs 2 &a2. ro CEILS ATT TSE RR BR RR EEE RR Rog ow IEEE OR HOW 8 oon AT EG pyre ve Et ens a HE ATC EU mam 2z g 8 IES sor a sn LL SLA ee ree SFE Fame ARE MH ros. 232] s. S me ys : } | s 3 IEsoon ssa so. SdLIA ree ree coiare co wens vw win 32 = N& WS EB Blok oe nam bos fs ss FABHEARY LASERS 4 : Ens aad 15 TIAA ve) te, on EE EE ALL gg32 s & JAEigIon usommtones perce. te. Rn min si -- corones 232 g & ennee a CISA MEEN ddGa E Fhiiili ERE E GY NED. a-gcteg1 Rf ES EE Bl eee a IIL ostaoi em om ls CIS As sk AkaTHe CEe LL SototBds"AMRE oIat ps08 88y4gd TRECnHEiAAnLLaESe eErARLE RE CELL ant SARS pceSA ER RBs UE ls yg Bi, cuisi my 8&B2 L ee UAorn sss nn os EE SE tits Rk monocricoig ieic 322 = 8a [SA em ET oc onan : EE AEE 3 : : : : RT sg pve. ve aoc a soirreer osrrions HHinRt ag es oEdEg Es E TRIE SIND, os srsmasviees sessions renee SOS SUS 8 as as PON Srio caenicierivi: a Teoma fog Add oR d Bo Ed mmm &s33 2] : ome Hl50 - Ee , rae wt ic bo CI ---- EESTI ff 4 1 3i33 := ort es es oer AAT EO TR i IL SREERE eng ne mo 833 gp sven un var cons ci SA ce ------"--g 184} mn 8 a 0 4 AREER] 238Boz 4 < pr a-- man ons i232 :. inp aaa A SnHFi dEdRBO dhA dhdh FETT wd ddd sg pp. ve rrr 1 31111 EE oe ro IIASA i SPEAR LR et 8 8 id EEE a Bio hoi ei AEE eg Hadad 32 . 2bBo og QS Tr EL we ir cas OI Rea idnoni ricuianceii 3. 2 A so TIS ey 4 4H on $3110 ER TG Owaug, 11100 10808 8} : HE m--"-- Hr Br sop os 7 ssnsc -- 3g2 =x -- oe TEAR Ra pegEiiiiig dd EAE HRHR fee ve UE 5 w A ns m a CLI SAT mse BIE EG EEE )- FEAEEG HdRhcision a --- Kad id ds iai "Ey hEdy Ed o3gEos { HE EG gre. ve a sms al so CLI SA ee I i -- EE har ona uiin cai 32 . &BF roi Y 22G 30 1 EOE A Ee EERE es co :::s|s 2 2 5 Tae0 Samir of Horne ta wi 69-100 et sow5i%n somi&e Wwe &h 2 wii en TT ar ma i Catratiol town) a(:o2 . : EeiTo w3% mi!e }:. wi*e oiman ho4eh :v: . : wTee wiNrh wi3g% .: wh3so mS3ah miGah oai3h SomPeosmiae leststersse oa/a) wwaaln5, mMeRr5. RmIaSwo , P eBmn. VmPUen wGhsein WehaenToe sReewis amlaiwIio!. PsBeaEsL b 3 faitl ereparfed with 06 high-dose. anes hrosghat treat. a:1y5 0T$sh :.: ""om agianfi, BsuaoIo, g BE -2 25-100 Table 34 (Continued) Summary of Hormone Data eek TT Ey Mo WoMTen Maemes Testosterone (oa/et) woseenns Aono oIaowsan To lo io To lweaens ase. BogewoFn zBnIzse 2 ses3s io iaesste eSshese Bseess: To " " swe W5 Lutetatzion (aa/s) 0o0sls 00021 0o06s o0lsy oosh 22280 5 We3w o0lsz o0lss 08 o0dss F0Es. os 5 5 5 50 Ww 002s0 [I W9 5o0o4r 00o'slo 0o0.l 05osh 0oogk s [iooth 2 Ww3en $o0.h4 :o0.is o0 sh [ 0 s EYo{ g ""w 4 Animals ere pair-fed with the high-dose antasls throvghout trestaent. - WW 632-100 Table 35 Summary of Test MatWearrieasl Residue Analysis Meek 5 M5eN an 8 HW9)m WooMn Zhe5Nn T -----_---- Sl8Gr0 opp (ppm 2 2 a ot 5 iI a 6.de5s 5m95.o4s a Y 7Lsm maesns aaowt71as ani2e ai HE 12 3L13e03 1l083d.5s 15S190o.n3s aa: owass io usees 0 a4 : 1nl0e3ds ur1n0 ee 4a: oLselte 3 oaeuss. 2: a AT] values were below the limit of detection. 122 0188 Theotroeet]ic --Lloom) i: 1 8810 33 fii100 wt 623-100 ResTunltRsodoefntNeFtohookd CVaelpdrastiiTeodanessfo3tr6oCeetreaninsatR ion oo f 1-5180 feafiit Tearrcegnta --lopm) --_ 0r.o0 Dav1 1s5o 0.760 &3younw i 8B0736s.a0 105.34%% 1a5083. w8on steitto 080. iov (x) $6.10 oi10tt0 3won 10s50 i59.31 hiov (%) :1.10 25. #wen Ji sfsr iov (%) 33.60 123 co1889 Wi 6328-100 TheoTro--evet!ical LJ 1:a6o0 Table 3 (Continued) ResiunltRsodeonft.MeTtohaodd EVxalpdreas(tsCieodontniansfuoetrdh)eDePteerrcmeinntatoifonReocfov1e-r5y16 KAasaalyyftRisecsaullts oar1 13oo7rm (Continued oH$enm V Thepoerre5cteinctal 10a57772 105.860 3 Da2v 1 -0.082 . - I1I1 0010.:.652528874 15s652.i.57 1.20 120 H3en 259.57 0 (x) u.7 11100 1065.86s 15E06.i5 H&einom 100$$0a0 V + Data are from reanalysis of sample. 1 0189 . Wl 6325-100 Table 36 (Continued) ResiunltRsodoefntMeFtohoodd EVxaplrieds(asCteoidnotni3nsfuoetrdh)eDePtoerremeinntatoifonReocfov1e-r5y10 TheoLraeevoteailcal EH3 11100000 t111.i0000]0 AAntaalyyotRoiencsaullts Dax 2 wf3so a5ad13 10s905o65 (Continued 5e'an ov (%) o5eanm i Hoan \&sD x ThPeeorrce5etnitcal a55633.0 s1s:50 31.40 31a.1 5Z2.i9%o i 0455s.5 56.8 333.870 12s 01890 wi 69.100 Tae 37 Rests of Stability Ansyses Gosnuioirtsgteens OaLiotfomito, ET. a i1 5rar we Pn teiTrriiogerpsteesr,sLuaee ln i1 Ham S5es B[8ion Fa on n1es 8ns rete, 2 weeks wD Soe we:' FrSadoe Bom H3Iam Blew B#I1lew froten, 1wets i:n| aHeeon wwiihim E i0es w + Vales in parentheses re percent of theoretical. TY S2n3elee 2j0t m Mi0nam 15020m a32 8 _8 Sitoragce Lika ie Sp Table 37 (Continued) T-- T umemm Loom mmm wo ee Heo Ble Fe ct cons ot soe er sr fron es 1 iz32 s. asulolles To wn won woton 4 Values WWE 6329-100 Tae 38 Results of Homogeneity Analyses pate TT B g g :1 SSoeammoenn mmoelmle mwaagsonh RoEoSn :| Soemmmmea lwarlge mSIeVsOeWs nHeIGw :1 SSoommoes emdeimeo siehaem) iwGm :| SSooeammeeas wRePnGs mNorlae) gIOmS parentheses are percent of theoretical. a n 2 F3 W wi 620-100 Table 38 (Continued) Results of Homogeneity Amayses lsoulmei Rite TL L ine Einmw *" :1 aoew lmeodr : : wnt :| C opommoa , 2, wa" n :| Co on g moe. : . sotton :1 oearnfmaee) :. sN 2 RBEeeaIsmuiEyszNersE,reTorTorneaan.:resamrbeybpiesrcoennt1o1f5/th0e1oretical, - 82 5 2 - pr To a e T mr n nie m g Ey mm JPoonamm n asnhaay aBm i mmime Co ;booiWmmEmYe e:o iEEyE wmamnE. nmmemmm :: a mm:: eeso aboosmp ; "1 * Lie tho S- E - :. 23 1 Hm es B @B8 oE= Title 3 (Contes) Results of ose Frepration Amys wi 632100 ,Meek 3|Replicate D STo sI i:- . :\ cso. -: 5 i) C oaeRmEmSa - :I wim :2: oT- o:- s. -: a n 2 :, .: o.z -: :\ C oermkmsn " }: 2, pweeay + Vlies in parentheses are percent of theoretical. 3 prpmoEoy -: .: - pRrS ey .: 2- 1%nwaeyd i: - : 0521302 :. -: APPENDIX rBrootPtarocoPcatreolo]ctooeAlcmnoeldDnerdvTmeriensanstttei]ohhnoo.s. 1 Protoce] Amendment ho: 3 Material Safety Data Sheet WE 6325-100 12 0189) HI 6329-100 Protocol Deviations Protocol wDiolsle Pberepraerfartiigoenr.ated"Alulntidlose preparations Sdninistration psDaormsepeplaerAsantaliwyioslnlesn.ibxeedt"aFkofeounrr Wfaedredokimtie1oa.nc.ah.l0ndeosseetsset of X06 Kept for at Tekst the am period eaanxnapdleycuztneeddde.r"tothebe saumseedcofnodrittihoensstutdhya,t atrheen ASbnepaelccyiosalillse.cAtneadl"yAsnainsda.lisqtuTooertsetdofMuantstee]rriuamalni.iR.yewssiiilsdlue for test material residue. Special Analysis. Disposition. "Serum "s7a0mpClesunwti)ll sbheipsmteonrte-.d at approximately eTaxensreamsnitgnhuaetitinioaznte.edd,wi"tAahnndimmanelteshcorxwoyipflslleudrbaenbee,tween 7:00 2.8. and 10:00 a.m. bGrroasisn Nanedcrosppsiyn.al When' tissues are Ccuotrd swuirlflacebse trimed. oefxamtihened Actual Procedure sDatduonrriienndigstWaretaetkrisooonn1. tthermopuegrhatu8,rediunettisl were NsfoaonnreeWceooefnkdtih1tewieosrneests sastoforweasdsampuulsneedsdermfiotxrheed Veeks taraugh 8: So's Second Vseteakbil1i2.ty analysis was done at 1Wcao1slhliesncegtrtiuoomnn seafmorprelehsosremnftornoetnoatnhHaealzylWseeitesok.n 22 The serus resaining after hormone analysis was returned to Hazleton aWanpiaoslucynostnissio.nf sfDeourreumtetsortemaanmiantieinrnsiguaflaffitcreieersnitdue hornone analysis, some groups. had serum from less than 10 animals aanvaaliylsaibsl.e for test material residue The location of serum sample storage dfoocrum3enctoeldlecatndioncandnaottes bweavsernoited. neTuxeoscarnoagpnusiiimneaadltsiaofwnte.erre Tnhotreeweiagnhimeadlsbefwoerree 10:00 3.8. Tnheecrosppsiyn;al the spinal tchceoarrreddfowwraeesr,enocntuottceosxlualrmeficantceeedds oaft when tissues were trimed. These deviations are not expected to have affected the results of the study. 1m cols: og y Lissa nnn LIAR WEL 0) COMING cross Cor st. paSpnonsiomr:esota poTocoL Tos Stugy Taste: 13-4eek Digtary Toxicity Study with T-5180, Ammonium Perfluorooctanoate act (CAS No. 3825-26-1) ovenDate3:, 1950 wHaPSade3zir0lsf1eootnroK,mniinWnsWigmisasLcncaoonbsnoSisorniua.ntt,iov$rii5yrn7:dc0.4 LabPorojre6c3ta 2I8d-1et0n0tioficratiy on: co199q PH9I3261328-100 Page 2 STUDY IDENTIFICATION 13-PeeerkfluDoireotoacrtyanTooaxtiecit(yCASStHuod.y in Male Rats 3wi8t2h5-2T6--511)80, Ammonium Test Hatertal Sponsor Study Monitor Study Director Study Location PropoIIsnne--dLLiiffSeetuTd(eyErxmpTieinrnaiemtteianobtnlaelD)ateStart Date Experinental Termination Date T(-C5AS180N,o. A3m8o2n5i-u26a-1P)erfluorooctanaate Tanoxicology Services SBtu.ildPianulg, 2M2i0n-n2e6-s0o2t,d 351C4e4n-t1e0r00 f3oger G. Perkins, PAD, OAST TSBtou.xiilcdPoaiulnlog,gy2M2i0Sn-en2re6v-si0oc2te,as 3~S5C1e4n4t-e1r000 HMaazttlheetwonJ.WisPcaolnaszizno,lo,incP.hD, OABT MPi.d0.isoBno,x W7i5s4c5onsin 53707 (608) 242-2622 MH3a3ad0z1ilseotKnoi,nnsmWWaiinssccooBnnossuiilnne,var5Id3nc7.04 HDaeycem1b6,er192501, 1990 To be provided by amendment 135 01900 1 study 2. purposes 3. Regulatory Compl tance 4. Quality Assurance S. Test Material A ldntsfication 5. frit cstv 0. storage Conditions Ourscteristics F. Reserve Samples 6. safety precautions HTFihWsotse6]33 29-100 S11630,k`AmDmioentiaurmyPToxiaucoirtsyorcStkusdntysawtisth 1. T(oCASassNeos.s38t2he5-2s6u-b1c)hroinnicMalteoxiRcaittsy of tsthe1etsesstt m1a3teSreieakls wihndentofedsvatfousrtaets for TarrhcaeicvtsoeerrcdsstatiinubocdineyliiAtWgytIe)hnocfybtehaeGnocyuEodnntvdoiuxLrciaotcbneomdreeafntfitoenarclyts Practice Standards. 40 CFR 160, OTAHrphsaeesezpruloarerptattrinooncwntgeiolcWloUPilrns,oibccteoesndtaIusunuriddensyis.tceccidono(enrS.ddb6uyiPcn(StctW),ehIe)iaQntSudhtaalfniidtnaayrld T-S160, Aamoniun Perfluorooctaneate T(oCASbeNod.ete3r82m5i-n2e6d-1b)y the Sponsor To be deternined by the Sponsor In 3 dry area, at room tesperature chiIonalmftepoorsWdmeiiaftttiihinooenn't,heotnhoySr`psLayoetnnshtstehorersmiacsthearmrieaatclhtoedrrsis,stonics AtsSapukormenensseoedrravneidStliSsetaromrbpeelsdeotmiorpnfatnes3iafocefnhrrreceolsdfoetrtt:hwoieltlhTIehneebsee rTt1ineeirntfausearicnnkpteiohidnra-gdsotueontnceo.esftthwetmhiaeSntpeosrnt4isduaodlryERwtAioflt1ieb6re0b.ert1he9et5iarine"hdey As required by INL SOPs, unless otherwise specified 16 0190% 6. Experimental Oesign A Antmals (1) Species (2) strain/Source ) AgeoratTreIantimteinattion " HeiofghtTreasttaIennittiation (5) Humber and sex (6) tgentification (7) Husbandry (1) Housing (b) Food (c) Vater (d) Contaminants (6) Environment (6) Aectimation wTPahigaet6)4229-100 Rat CrI:COR/Charles River Laboratories, PThraenf'erawbeleyks4 to 6 weeks, but not older Approximately 75 to 250 g 320 mates Individually nusbered ear tags Individual Certified Rodent Chow #5002 (Purina Mills, Inc.) ad Tibitus, unless otherwise specified. The food is efnovrirnountmreinttiaoln]conctoamaatnneannttss. and routinely analyzed by the manufacturer Ad 1ibitus. Samples of the water are saonlaildysz,ed habrydnWeWsIs,forandtotsaplecdifiisesdolved TSareeglraebnciatgeahdioasepglhieamatelenst.sc,onatnhedenatvchylaomnreditnefalotsre,d hydrocarbons. ThfhoieosrdeSotraurdaeyt.neorkntohwant cwoounltdamiInnatnetrsferien wtihieh rEE oncvairwot imlelntbaelsectonttroolmsainftoarinAthe3 nies] ThiuGahted/it1y2-h`oofurS05da3r2k0%e;ycatda's' 12 ous At east 1 week w 01302: WTPPaEog3e261329-100 (8) Randomization Via computer-generated randon numbers {owffo1Tr1)thaebnsoestiawgneeniixamgceahenleetsdd.st+oe2leTgrchsotetueapdwnsed.iafgrohdrtTdhteevhveairaainstaittmutdaiaylonssn woefigthhtesmeTaonr weeiicghhtg,rouapndwitlh]e mTeotanbebody 5s%taptriosbtaibcialliltyydilfefveelr.ent at the (9) Justification 8. Group Designations oeuTfsvheaedl3urartaototidoecinnhstarsfatrscupetdeqeicureieiesnszt.elaystWhauaeslereedefpfrrieeancsttsessnatafaroeteftiyvtehe test material on testicular physiology. Group DolsoeomL)evel oMfNaulsbeesr! 1 0 55 2 `3 1 55 3010 555 5 6 100, 55 [4d a5 411r03ecwoaevneeikrmsya,lsantihfmeoanrlstG)rroewuaiptlsmlen1tbetwhritorluegahtbeeddif(sodcreosniatyginnajuteeesddstaasnd tpfohererysiatswtieTlnecaesb,te 8oorbwsdeeeerklvsaeydepdofsotortcrcreuearvtremeresnnictbe.iloiftyt:oxic effects b ADaunneiimmaatllossthi(enGroGpurapoiurp-)f6eetwdhiirlnolgughbroeeuqtupiariterhne-efnettdrse,swittnthehnetpthaeperrhiiogfdho,d-dose control animals (Group 6) will initiate on test | day after all other groups. . Dosing Procedures (1) Oasing Route Dietary (2) ReaRsoountefor Dosing Tsotudcloemsirdeosetdhe 1ntesa t sidamtialarwitfhashoitohne.r (3) Dosing Duration At least 13 weeks 138 01302 (4) Dose preparation (5) Dose Analyses (3) Homogeneity ) stabitty () Routine Analyses 0. Observation of Animas (1) Cageside Observations (2) Antesorten Observations PTWhiIag3ez'6]329-100 DaWeocesckeolrydc.ionngcAeIntDtoradttihieeotnsastwiiwnlilgll pberboecneibdxauesrdeed.on udtohnsete'it1ep"srbteepnmagartaetdriiiosanplsenswaeisldlsuipbneptelireefdof:nrdigeATr}ated Containers: DaBiysrseaIcyNteLodr:atAddtihteiodniaslcrestaimopnlesof matyhe beStudy TmOonipex,edsbaomftoptrloemW,eeeakcanhd1 ftwrioolmloaplb1peosdtioanskgeenslieFdvreeoslmsotfhe wttiehlseltdmobaseteesrtpiorarelepdarcaoitnntieo3nntf.ranedeAzlea]rssausnyitenidgllefsor alyzed! FftoaorkuerNneaefdkrdoint1.ioanascO]hneds$oe6st5se op1fr1e1psaarbmeaptlieaosnnalwyinlsilexdedbe tKaenipattheafnodrdayu4ndoefTreamistxthientgh.s"eanesacOmoennedpiesreiitoondwsilo]fthabte wtarihele'lnexbapenescistytezoderde.dto ibTnehseusfreredemeazifenarirngtahndetesatsussdaeyyt:ted after 2 and 7 weeks. AweTeaIeckhdwToehseeekreparFfeotprearrt,ahteioonfneisrstwteislt4l mweabstekesra:isaslayFdeaodcshe Concentration wil} be selected wseeeqkuenpteirailoldy.wil]Sambepleasnilfyrzoemd eaascha4d-roup with a sample of the control diet. SMdioagrintlsaylio(tfayrnp:oaonrdandmheosrpii.tbmhu)n:dorityAdpdnacorhrteaicsoktnstteice aBbeshearvvieodr.S11 be recorded a5 they are Abte lreeamsotveodncferowmeeiktsl'y,ageeachandaniemxaalminweidl.l 19 co1c0l (3) Body Weights (4) aod Consumptions . Spectal Analysis (1) Hormone Analysts (a) MetChaotdiecotfion (6) Disposition 1 6329-100 FPi9o3e21 Before initiation of treatment, on the tfhiersrteadftaeyr,ofantdreaotnmetnhte, wdaeyekolfynecropsy Daily for the animals that wil) Crfbeeecropevaie:irrs-,ofetdGhrro(uGpiroiSupiasn.i5maalnsdrwl6i)l;]ywebeeklfyed Sianentrieurmmvaasrs"amspFcloheresdualwmeiidvliftboser testosterone (totd]); cosfoalcelrxeitfcritecegedtoafrtr,omeach and: peteinizing eh1a6ocrhnonseci:hednuSleergdumsascSarmaipcflietcseedfxro3imi rbaendom at Sdau'nraiilnnytgzaeadtlr/efavrrtoomsuenpeta.c1h11SsaabrceirnifainscaueTsppeteensdgeorFevraoln Rreecuosveedry.forThtehe fRoolrlmoewniengammeitlhyoadisa will ELsutFtreaaiddniiiooztlimnig-noDhsiosarsgsenoyenseti-c Products Kit Tes(tDoPsCtKEe2r0o1n)e - Diagnostic Products Kit (DPCTKTTZ) wiCNnioodtlnhlfSeatcssottereeteddhdoxafyornfnoirnmaatrelteash.neew(;idsleplsbpclreobanoerddiiannwnegietis}etvlhenebsteiCzc)eadva nts] Caner ton AStaToepT!rpurSmoaxmispmalametpselleysWiw7i0llbCebeSuhnissttpoerdesdhoinpaeteenrty. ice cDTiremenuntnteocSHheoervnvetilsclteorsy SDeicvtiisoinon VH5ai2z0el0westL:oeneVsiWbruagrsighniinTag.otronnp"iEkies wo 01908 @ TesRteraiteyrssis ) We2stietiPantemiton . Toraination () UnschedautleedsSacrifices @) Scheduled Swcrifice 6. Postaorten procedures (1) Gross Necropsy ajidos6325-100 SAeiglneasaoufsivpero,set"estFersa,t Teunneg,itnecah SCnsarottiootvrieniddeToetchdrforlbpoyszyentShpweiorflnolesSroonrpcbsoetessmscoioea rblt)llheeoctaaentdaoslyaehsynidis trfeor TFRtoaoratnyrBea:iss)ilietrametcsoasftoedembtrembaosreerr HApfasiemrctaitonoaaofttlivieerieR,1ie)nbecLhcpIetaaTint]ed CSFFioinsvdeaeotnipu3no2sneedaTacoshrettsanheediriTntegnvetlgo:ohnFeorSpraeptleaecscttosn 1 Serosaans pratiferacion RRNcoriEoopnEsdtescownidrerbSoen deonecon 411 animals SAeHfEetIserortheeas,rt ,taeTxedasnasintisuh4sinat7t,1et3n,gdardn1ad3snrwieewnssiipsoifoeed Settee 1505's ine Torog seer frBreeercstotavoeannrryt.ataaniniegmraalotts Jf(1oe0n/tdgrohupwt)e,ekhsthnisownilel aneEe! The necropsy will include an ESBExhiteeorrntaatlcaSsoiuvrretfylaccees of of the the bogy brain sna aTotme)dSoherrteteTbureFacoerr 1H1imo.e) ww c0190% . (2) Organ weights (3) Special Analyses (0) Tissue Preservation PTWaeIgzee6l9329-100 MTahsocaralavciitccia,evsiatabynddoamnivdniasplca,erarmaaansdalpelsviincuses pFtahoierreefdaoclholrogwaainnnisgmaliorTga]atnsbsecwhiweledliuglhebededwseaicgrhiefdi;ce, Separately: LBLurinavgiesnr ATcecsveteesssiscolrey, sepxrosotragtaen,s c(osaegmuinlaalting gland, urethra) Oacarrlggcaaunnl--atttooe--dbb.roadiynwveeilgghhttpreartcieonstagwielsl anbde ffSsoraurombmpctlueeetsasatcnheomofauatsnleiirmvaiaedalril,pfoorstereessitwpdeiouslse,ls.ibblleueAnngcsao,nlalleaycnstdiesd `acdodlilteicotneadl frsoemctieoanch ofani1miavler fwoirllposbseible OaSxenicadtlaiysoseni)s.6.of.Pal3.mitoHyelpatCioAc. Pal(mSieteoyl Cot Tthheerefoofl,lowwiilnlg bore rcoelplreecsteendtatainvge samples Sppfarormerepsmsleaeelrrsivvnee,ddofuiinnntlhgee1sls0seu%tatoprithashoslesudrpeewhshiaystdeweei-lbs]ufpoferbfcoiefrfieuedrdt.her processing 1f electron Bicroscopic. evaluation is desired. LBLrieavsieinrons ALTcuecnsegts:essory sex organs (seminal vgleasnidc,le,ureptrhorsat)ate, coagulating 10 0190 (5) Histopathology 7. Reports A. Final Report (1) ExpaendrimMeentthaolds Design (2) Results (3) Statistical Analyses HTHPI93261329-100 Page 10 Teshmtebaeindaedbdeodvweiitn(haspahreaampfapftrioonxp,yrilaistneec)tainowdnieledlo,sibne, and eaxnaimmianlesd fmriocmrowshciochpictahlelyyarferomcolalllected ATimfiitnaeld troe,portthosienclfutdeimsng,1isbtuetdnbotelow 1dr1aftberepsourbtnitatnedd.twoOcnoepiceospyofofthtehe final report will be provided. Aasmenddeafeinntesd, byandtheanyproptrooctoolc,ol pdreovtiocaotlions MAnotretnaolritteya observations BCoudmyulawteiivgehtsbody weight gains CFoomodpoucnodnscuomnpstuinopnt on POraglamnitowyelighCtosA OOrrggaann--ttoo--bbroadiynwewiegihgthtpreartcieonstages MMaiccrroossccooppiicc oobbsseerrvvaattiioonnss BCoudmyulwaetiigvhetsbody weight gains OFrogoadncwoenisguhmtpstion OQrrggaann--ttoo--bbroadiynwweiegihgthtperracteionstages PHaoirmmiotnoey]AnaCloyAsts wGirtohupsGro2,up3,1; 4,Graonwd 6 wwiillll ith Group 5. Statistical bbee ccoommppaarreedd methods will be those used by HMI (Attachment 1). us col 308 (4) Data to be reported (5) Analytical Chemtstry 8. MaiRnetcoerndasn,ceaonfd RSapwecDiamtean,s HTHeI93261329-100 Page 11 MIenacnidebnocdey owfeigahnttsesorten observations HMeeaann Hean ccfooumosdpuoluacntadinvsecuoanpbstouidmoypntsweoingsht gains HMeeann grPaoluapithoyo]rsoCnoek values HHeeaann Mean ooorrrgggaaannn--wtteooi--gbbhrotadisynwweeiigghhttperracteinotsages IInncciiddeennccee ooff mmaiccrroossccooppiicc oobbsseerrvvaattfioonnss Ineidaniccvhilduudaaenlimfaaaltn)etenaondrtednateobosfervdaetaitohnsfor(to IInnddiivviidduuaall Individua) fPbaoolodmdyitwcoaeynilsguhmtCpsotk fvoanlsues IInnddiivviidduuaall oorrggaann-twoe-ibgohdtys percentages weight - IIInnndddiiivvviiiddduuuaaall] ommairccgrraoonss-cctooopp-iibccraioonbbssewerervivagathtitioonnrssatios Methods and results (if done by WWI) Obareuidgiaitvniaanilglabdthaletea,asttuodrWyWIcdouptrioiensfgactihiletirsetoapftr,eogrweilsls raenpdorbte.forWeheanccetphteanfcienalofrtehpeortfin1asl mccaoogpaynpleetoiifecdat,lhleyalfliennacolordigeridenpaorlretcoprwadipsle,lr daantda,4 be all SrspepotenacsiiannreednstoiwnibletlherebeatracithnrieavdnessfienrorfaecdcWoIrt,doantcAhelel with 40 CFR 160.195. I 01 30q PROTOCOL APPROVAL Wi 6329-100 TP9321 Page 12 RSQtougduyerMaontd0tPoerrkA ins, Ph hD, OABT w Studcy hDierectfor h es wr Toxicology Hazleton Wisconsin, Inc. Cole-- Quality Assurance Unit Hazleton Wisconsin, Inc. n-- e12/4/-- 50 -- we ne fz [te : RECEIVED DEC 0 6 1990 HLA-Madison us 01910 PT1aagze 6)21329-100 Attachaent 1 statistical ante The statistical methods that will be used are described below. Levene' test the variance, (Levene, 1960) will be done to heterogeneity of variance at p test for variance homogeneity. 5 0.05, transformations will be In the case of used to stabilize KAbtrnreaaatmlneeysersfniosrtemgsreotodfupdv(saaG.trasni.easnceaInfd(tAHhNoeOwVeAAl)NlO,V(AWi1n91e75r6,)Si#g11n91i71f1i)cbaewnitlu,lidbCaenfedosor.nepaanigornaHitoahweeechooNmmooedgrsefnioeioonsussToorrey NBOEonIdeGy-hwEaeSyi:gMhOOtrVgAignai-wnLislo;]-bofbdeoyoduwseecidoGnhs(tuimfpptaeprfpoclnesin:ctaabPglaeets)attatoonyd]aonraCgloayxnze-aindab-obdMryaartmwyoenitgwhteAsp;nsliceusrmeeut.liaotosirveeen hcIIoonfmvitoatigrhaeielnaenMicMbteoOydVyA(uCiws1Oeh1iVogwAhbs)te sdai(osWgninentiehfrei(,csaecneo1cv9ea7br1o)ifvaoterei).1b1ondoAbyletwtheruoiasugneghdshtfsofroLmeaavtataninWaoeeln'eyssksewt0i,eblso)ssoynebfe-wowreaursyogenrssaininaibnloecyLseseuihsseoShfe PscaioigvrnawirifiisacenacneCta,mapdaGjruuinsseatsnesnatndbertHeowmweoeevlnelsgrHxootudrpiasfn.lceodusTukheetye-rKorgaemneerittyo.t w1illthebeANwEootuAfor Grow comparisons wiTl be evaluated at the 5.0% two-tatled probability level. References UGanmeeqsu,al P.N'sA.,andan/dorHoVwaerlila,nceJs.: F.,A M"oPnatierwiCsaerloMulSttiupdlye," CoJ mpao risounofPrErdoucnceadutarieosnl y)w'ith SLteavetnies,ticHs.,, 1(2):113-125 (1976). Robust Tests for Equslity of Variances," Contributiotnso SPtarnfoordbUanaivbnedrisSittlaytiiPsrtteiscsys:, S(teadns.f)ordI,. OCollkfionrneita.al.(,196C0h.). 25, Pp. 218-292, BMeisniearn,, 8.SecJ.i.nd"An4a,lysCni.s o10f,Coppv.ari7a5n2c-e81,2", SMteabtriastwi-cHaIlT PriRnocwiglTeosrT.inTEoxspteroinnental 1). Miner, 8. J.. "Design and Analysis of Siagle-Factor Experiments, Statistic NPerwincYioprkl,eseiwn fVoxrpkeri(m1e9n7t1a)) Design, Second d., Ch. 3, pp. 149-260, McGraw-Hill: } ue co191f @HAZLETON WISCONSIN WALT I se Com rie orocoL e921 13-400krDeirettiauroyronTcatnaimcTaitteyh,Set(utdnyhowi.tha1i-g51801, Ammonium Wi 632.100 Sponsor SBToeEtRcRotoEny sTeSrEvTices ww conter Contractor REadKhsanne,maai"n SS5o5catsaiar -- RSotguedry GM.oniPteorkrins, PD, oAgT MSHtauetdtyhwDeni)r3e.cmtPoarllazzeo, #o00o, ooseT Jsedient Ho. 1 This asendnentaod fies the felloving portions of the protocols 1. Erfective Gacesber 10, 1930 Bo Bratsaer.iti6R onCgSeernit, emnecnealdbeoghin,TeCh.yDobse ieng procedt ures, (6) se AI) dose preparations will be refrigerated anti] adainsstration 01313. PAangeend2aent Ho. 2 WH 6325-100 2 SPeca)csteiFooonulia6.nngdGrAoneeaprlliyansceeenst.wailthToDetshCielofanr,oilfyClowTihDneogs:iancgtuaplrocperduorcees,sur (5)geDotseetrdniyslvses ecAEaoaIcnchched4nwotes-reeeaketpkirtohenpeperarer(iaasfotetdileoerwnc,istlelwdtihlesbleeqcuoabennetnartlaoiyslazslealddyyie)eadtsweiaaalcnlghdroabwuenepee.ckotleflsoetrctmteahdte.erfiiasr]satmpdio4esseweefkrsom 3. ABansaely$s. e.6. Tooercilnaerinftya)theDesaicgtnu,al 6.proPcoesdtumroer,ten33dprotcheedusrreoss.rTio(3)ctSpeeecsitail ons: (3) Special Analyses(scheduledsacrificeanimalsonly) . PPTraoegtsetesor.nva:t6i.on.CxpeSreinmteenntcae) 2.DesiToon,ClGa.rifPyostthaeortpreontoPcroo)ce:du0re8s.The(6)erTeisssuee d as epSvraaemlspuelaretvsieodonfinitshgedlseuestiatrrieasdls.dueehsy(dsechfeodrulfeudrtshaecrripfriocceesasniinmgal1s1oenlleyc)trowinllmicbreoscopic EffectiveDecember 31,1950 S faTfoogrei6Dnic,elt6ud.e2,CtxdhoeeelrecitonelelntethcaitslioDnseescottfainorn.eCtae.nnDdtiorosenipnlsagacmPeprloewcsietdhaunrdtehse3.f(soe5ic)otDnodnoisnogem:Amnaaelrytsiecss (5) Retention Samples (6) ose Anatyses (2) Homogeneity pdfSiroaeermtppalarte(asptrTiweeoimanlisltx)an6bdeamnodstntatokfhrerseno,dn fuerinnaolcmehastsdhfoersueeseb.ezadesre for rSaenttauuldryysnieDsdi.retcotAottrh,ethe`Stphdoeinsssecorrseatmoirploendsisowcfialrt)dheedbe DBaiysrseaHcyIte.odr:atAddtihteiodniaslcrestaimopnlesof mtyhe beStudy mOinxeedsamfporleVeeaeckh 1 the top, bottom, frio1m1 4nd alble tuo odtpoapskoeesnilnefgvreolns Dasusiesdeastyoedofa fcotrhhaentgedesotseimnaptrteehrepiaamrliaxtiicnoognnteanntd Wpseraeomkpclee3duwrfierlolmFortahlestohe1 bep1 patpaoknleenvleelfverlom,mixetodnnee for tt0he9es,tdmobasotetetropimra,elpa`arcnaodtntiteownnot.oanpdpAolsa]issnagsyaersdgildeefssar of wainlallybzee.stored in 4 freezer until 148 0191% APmaegnedsaent No. 2 6325-100 (b) stability () Routine Analyses maSFBeineotxaulertydWaIzkaTeedf)dnodrioBtfenikroeonstknaheklepeta15dcsahfeyotOrsdnooefasotefmsieTpsxteraiaemnseppgti.altecisattheiwboenioelnslane CuTPhoseenerddiiortdfeiomoraonifsntihtneitgnheastttuuaoda'nyr,eSeutnetsdhxeeprniecltn{}eandelbyestsouemssetp:eared i03veefrleezer and assayed after 3 ong AwaenexIeeckhdteowTshseteeerkempaarFfetotpreearrrti,ahaetitodhFnoeissresctowinclt4olrnowcleebenektdsria.easttsiaoyFsneaadgch cP(oeSlrelileoecdctteiedd.i"lsebqSeiumepnaltneissailylifybr)sonwaiesias]chgbe4roovueek AEKOHENT APPROVAL R"ec2el8v-9~- CTalgeor.iPePrkuinso, PiIDs DSTMitpliomaHtoen,itoArBT mie1/17/51 WHiaszcloentsoinn HDiaptlcohmesste3,. FABiTTetes Zh STtouxdiycolDoigryector Hazleton Wisconsin, Inc. plesl los QRaudalleittoynAWsissucroannscien UnTiet. a(AD0M/1]1e) L 2d, L ER us 0191 @ HAZLETON E RESnINsS LN HHI 6329-100 rom oan 13-MeskeDriesTtuanrryonTcotxPaiRmcOeiTrtOtyCeOSLt(uTtRdPayh9t3osw2ir1th20T5-051S8001,1}Ammonium Po PM2trons Serviens SBEu.ildPianugl, 2H2N0-2$-50124,4-130M00Center HHI 6329-100 Sri SH3a0z1letKoennemWainscoBnostienv,arIsnc. Madison, WI 53704 Study Monitor StudyDirector becba B biibui biid idi iids odu i Roger G. Perkins, PhD, DABT Matthew J. Palazzolo, PhO, DAST Anendnent. Ho. 2 Effective December 10, 1990 This amendment modifies the following portion of the protocol: LeBiitah to"tismntiy Deut. . postoSustonrten procedures, (60)1T0igue Ffeoprthpcoesswibilte Sehlee:ctFrootntormtiocnr:oscopic evaluation, delete this section and 9) Tissue Preservation FTpSoharremenpselefteroisvlnel,dowuiInnnlge1Tos0obes%rcbporthtenotpeserrpceuhtstaeescnneetamatetesiorvereeesrreicds: 1bJ rahin RTseehrsteyhssion(yonevexteastniast)at Vesicie, prostate: c(saemsitnailng gland, and urethra) $lse Sitter . Ge'muny esas . fires: vniies <rgsi- 150 0191 Anendnent No. 2 Page 2 Wi 6325-100 aSTS(roasremcirphelfeesedoseuraltpepohrdrfeeesstevpharreacvorrecifasefonsilttcliiieonnwddSianntgi1Iom1FratlcSeiseslsssetouoecoenrnslseiyrn)de Jjbriainn p RTeesttresii a(loneSer stesotrigsa)ns (emia) AAENCHENT A09ROVAL hSBRoegsettohnan:ipeeaRrsoeTr= es Fos 3 ww 1/28/49, Matthew J. Palazzo: hD rSSisytaonsBteisr,ecrtaerr Hazleton Wisconsin, Inc. 25/9 Date A RTUTrhEeaKlasoeue rtankckeF .unit g [lan/5/ ais (ADH/J1e) Received NS 119 WHiaszcloentsoinn 1 co131p @ HAZLETON mio WAS EO NSLN PROTOCOL TP9321 Ibe Dlatary Toxicity Stuy with -510, Amant Perfluorooctanoate (CAS No. 3825-261) wt 6325100 in Male Rats Sponsor El selfing ce a, Toxicology Services Bufiding 220-2-02, ns3M C e nte r Study Monitor Roger G. Perkins, PhD, DABT Contractor Hazleton Wisconsin, Inc. 3301 Kinsman Boulevard Madison, WI 53704 StudyDirector ene Matthew mae,po, J. Palazzolo, PhD, DABT Amendment No. 3 This amendment modifies the following portions of the protocol: EffectiveNovember 30,1990 1 PJaegreai2n.a_tSiToUnODYiItDeE.NTIBFeIcCaAuTsIeONt,hPeroFpinoasleddSitteudoyfTidamteatacbollel,eEcxtipoenrihmaesntbeaeln dfeotlelromwiinnegd:, delete *To be provided by amendment and replace with the March 29, 1993 EffeAc prit) i 8,v19e91 2. RPeasgied8u.e 6A.naElxypseirsi,nSeennttalenDcees2t.an,At, SthpeecStpaonlsAonra'lsysrtesq(u2es)tTetostaMnaaltyezreiaslemaannd for test materfal following: residue, delete this sentence and replace ththe An aliquot of serum (see Section 6. E. 1. Hormone Analysis) will be collected and stored until analysis for test materialresidue. 01317 Amendment No. 3 Page 2 AAMENOMENT APPROVAL HW 6329-100 RogerG3 P\erkins, 0 Diplomate, ABT SWStudy Monitor latthew J. Palitkolo, Diplomate, ABI TSotxuidcyolDoigryector Hazleton Wisconsin, Inc. Ee Quality Assurance Unit Hazleton Wisconsin Inc. f3re/20/43 oy,[22 Date 7 153 01914 a3n0 cGoennteerral oteices SbtiCineaanka7ne3t 3-000-31331-0340-012000 Bmaarrnensznaeersaree FacsinuLe corr HWI' 6329-100 e eeeee STSRIAVLDIES.IONNA:TWEI:NNGEURCSS1TR41I30A-LGFELC1UH1OE-RR0AL0DC0A8BL-r0anPdR7O0DF-U0aC2oT1rS1o-c0Bh3Ie4Vn7It-Se0IeO1hN8-S0u7r1t1acotbumnit- S1U8P5EERDSVsE6D-E0S2M,1a1r-e1nS52u282,.9271,298071070882-03904 SOCUnENTs 10-3808. 1. noreorens caso. recon [vaiaop at pTr e aoun MNsaCacaorrnisiuounrayiFPaeatrreftliuvoorraaiuliyil | Carvorriat WISEel | 75.0-190.0 01 M3004 < 3.0 0.1 sare Ten acamn ages Tee an MMsmsCaooannriiouuraarifPaeatrreftlluioorraouallliyyll ISA EN-US Carsoiriate . <0 61 sgses Th 3m <ih8.0 0.0 svees Te Sn =SOA3U8R0cCEa31orAEsxcepxrePivocasrauenmeCSouLntItemorIrtTeinntceaes sot Sovarnsental Infuntrial Wrgienists 2. Pasion wa VBvAaOPrLOoLRnIp0DrePsOuOmeIsI1T21oM2.v2Y1e1TLn11A0LL1eI1Ce.0.Lns WWWaAa SESPUOENLCPOIONFATILAICTTIYGOONIANT VITTTELRvE eoeooooeos seeooiesss W501A603939-0.300 huts -- PVOELRACTDITLEVOORALAbGAeRsTeoeIvsvvLvnooeEerors WWDA VAIPCP(E6IA:Re3MvAeCdErair4eso6sutcS)rosoko:nsLeiegshancsolWorDed ponders slight odor. 3. FIRE ma EXPLoRON WIARD PATA FFPLULAmARASMRBIPILLIITTOYY L(IIiNIiTN-LUEETL1-Eoo: eWoaheFlessirie ETxTaOtiIero,TuIFoossws,TrCEb0iZEa.eRBrAy TCrAesoEt:calWD BE 154 c019q freee race 2 3. FIRE AND EXPLOSION HAZARD DATA (continued) nSrPasinocein.ns tFFaIIRRoEE FIGHTING PRCEIRESS WO EXPLOSION WAZARDSH Reativiny oaTa SDEraOyAiTAnMILSITtYas MIERIALS To ava1Ds VVAATZThaAoRRrDDaOOaUUlSS sDPeOEcLCoTOuRRpEPoROInSZiIAtTTiIIoOOnNN,aPaRyOWDILUp)CrToSdN!uocteOctcourric asterials including H- 3. DwiRowneNTAL ORATION PiTGunhseueeprnivenesgsporcwoetscspiouutnidosnsofrwomateorthetro asveocitdiondsu.stiUnsge. tCoortitecdtustpimtuisekd, Use set RERSCieOxmrEiwNaiDtlEh.DfPlDlIaaSmcPaeOaSbAliLshS s+atcelroivaels container: and incinerate in an fneustrial or TTCaootonensser1c7sioaTtlautuiafoianncsgilio1tc6yc.u4rscC:uosstbSeaierncstetieornreopturrioeadstuticaoemnsnstwivsle7lrerteeiensccolnRuvodevelutcWeF:epdplDhalciahcceahrraetrsgee ew1TieRaiOsmtoEiNnTaeAnLs or svinoritive DATAS setors dispels Ud E98 Mareremus Vorte AGCLhrCeeTieacncahlDierOaurusynsgdenS(I400DBeEs0aNnSdLy M(PCyOeBk)r1T:eMoC1h3.0(,L70CF0asianqeF/algduDesRyiiin2)n0o-ndS(aePynitaiMsoopnchha(elLaeosspcoanlts SARB(Arcoaunteaizeaasrrry)s CwLa7a4igsahnsts)g, tGre4e0n-4AlgEaEeS,(SeDleensasiiressegnceorpri6c3o3rmpuiiusa) 1763-asypreG30 FIRE NAZAADL No. PRESSURE: No REACTIVITY) No ACUTES Tes CHRONICH Tos + Svwsesrin Fine i eeTacsoeonsmaiaiacctiteaslny.flush with plenty of water, Continue for 10 ainetes. Call sneeWiaanisahCornaitfoafncetcsted ares ith soup and water. GEP 1STLIyOah pNtons d occur, resove person to fresh air. If syaptoss continue, ovC5ea0n1l4'FG4IRSpTThOyUasCitEchiavnORIoTrINPSoLisoinveconctarsoilousCesnatoeurnts of mater. INEDIATELY NoSabrreveivstiiaontsisonss Wpb - nnaet DDeeteerraainieneee Wr boet avsmetsiieacntaenis hades id . 155 01920 rE ain E -- a3 6. SUGGESTED FIRST AID ne PL" LeeTeIneotriilmeveeSasailBLauiveeneeekeetTaiweriseetssrtoarnsoaemaltweiav2htnsoeotttPVsiee0vieopnmotiuTeerschsoereetsEerieervoeeetrntee aunt C ppslperiE datiptn gd aTahlaSseebn aai tmoall atite on ht orht ahhedatevdianesecewoepntpoedrdei.rnersovesm sessd NrOoi TcEirFotEp rTtEeiitynbeeSsoefkoeuntaelbdoi,nnee RiennaedTAyL atetnhaseein ghsi ShTieaanb im iAyk eSF EAEM MTReOL rTetTioou Bubba-- shoves protective clothing. Rbr EC TaRRr ToiR ROlTECgTIrONeTAexetendustt iortsueppllied SERN air respirator dust Te ree norco JR---- FE poosrure Leaems wio Anncniun Fertiuereutivt Garborylate 0.1 sel Tn Sorurcee orSMEeexaraorsnemeStLooIvNveIrrTeasBeansTheot Gavarosental Industrial Wpienists wan wae re Er COTA E183 eon Be Freiveving ve. vi sen apm Firect eomtect. pfeAnrisviaeplinsitTuadnerireseabinaedeyicautAvepeiFpCel-ber1ae43gi{nssX esrodeerrnuaetmb ieislkpyinAigrrb oiFtgatsionmh gmesa t.o othvreacetyoeo:s. oereioetinon ao atneeeTEee ChHeSovecraentr ee SsoovptriiedaeTreosesreLrrsorveeoshprowtoirosne obyr 4 RreeepiersraaersthureTrootneasmttitoeonlteheexpToSehseerrreeev-eeprsoheete(eetrodoeoaoiActoevreans vser Suitreesteasteprried EE TTI Toth Tetat So eisatie TleS or 3M HWI 6329-100 Abbreviations: ND = Not Detersined WA = Not Applicable 156 co19zf 1r8inE1e3 ta rns rae Stans 8. rHEeAcLTtHioHAnZsARDforDArTAows 1(co5ntiynouned)str roe 3M Hl 6329-100 Mvreiationss WD - vot bteraines wa sot appicanie PToieniIoantearsaLtieoeonrheinseBets SinheesMrreehprienseonftsisusr Sceuvrerreanlantdseondsebroet BI Ie or Rh alve wind ns teri in osbEmeCion th or conditions. Any use of the ssterial which {s not in conformance with this 157 co1b2p, Wi 6325-100 wore 8 Innddiivhviaiddtuuvnsit)duAFsonlotdeondCooryntsewunemipGathnistoesnrva(toiwon)s NOTE: nTltyutoabaserrvnattieomnssrioetnherobstehrivnatnioornmsataarveieirndicated in the 15 0192% wr 6323-100 INSDRIoVuIrDUA1 L"A0NTEBMPONRTT-E5N18O0BS=ERMVAALTEISONS mNOiRBnEaR ueek osseRvATION Location ust 6 aeGsaiez a3 uss a aesae i2f Gass 8 earaese 20 aust os Gases oGases s rao 14 aaae 23 Grae 14 a5sH 3 Garacesda eGaass Gus a33 eras 8 are cass aes INTERIM SACRIFICE 01/25/91 AnLAoLroeccciLaUSION RECOVERY SACRIFICE 05/17/91 RECOVERY SACRIFICE 05/16/91 aTEcRoMrIeNcAtLa SACRIFICE 03/26/91 INTERIM SACRIFICE 02/14/91 RcEhCmOoVmEoRDYACRSYAOCRRRIHFEIACE 05/16/91 INTERIN SACRIFICE 01/24/91 INTERIM SACRIFICE 02/14/91 STHEARLMLINAMLOVASBALCERIFTIICSESUE03/M2A6S/S91 TERMINAL SACRIFICE 03/25/91 AIvNoTrEeRcNiaSACRIFICE 01/23/91 TERMINAL SACRIFICE 03/25/91 aIcNoTrEeRcNiaSacRIFIcE 02/12/91 aIoNrTeEcRiNaSacRIFIcE 01/25/91 EAIoCNTroEe0RcvIiNacrSuAsCtRIFICE 02/13/91 INTERIN SACRIFICE 02/13/91 INTERIN SACRIFICE 01/25/91 INTERIN SACRIFICE 01/23/91 INTERN SACRIFICE 02/13/91 RIGHT EYELID HIND RIGHT VENTRAL Neck 159 01924 INGDRIOVUIPDUA1L-A0NTEPMPORRTTE5N18O0BSE=RVMAATLIEOSNS HUI aNORtBEaR vee OBSERVATION Garo 1a aan ee eee carn 1a Gare 8 cas 1 eausree 84 aan 6 eaaores a8 efGaaas at33 eases eras 8 earaes: ak eariass 16 cases crass 1a eases reer ua cass is erees os Gann TERMINAL SACRIFICE 03/26/91 RECOVERY SACRIFICE 05/17/91 INTERIN SACRIFICE 02/13/91 TERMINAL SACRIFICE 03/25/91 INTERIN SACRIFICE 02/14/91 TERMINAL SACRIFICE 03/22/91 mTaNLToERcIeNLusStAoCnRIFICE 01/25/91 INTERIN SACRIFICE 01/25/91 aIcNoTpEeRIcNiaSACRIFICE 02/14/91 ARaEwACoLOroVeEccRtcYaLSTUAosCnRIFICE 05/17/91 INTERIN SACRIFICE 62/12/91 INTERIN SACRIFICE 02/12/91 TmEaRLRoIcNcALLusiSoAnCRIFICE 03/22/91 RaELCoOrVeEcRiYa SACRIFICE 05/16/91 INTERIN SACRIFICE 02/12/91 TERMINAL SACRIFICE 03/22/91 INTERIM SACRIFICE 01/23/91 TERMINAL SACRIFICE 03/25/91 TERMINAL SACRIFICE 03/26/91 INTERN SACRIFICE 01/20/91 RECOVERY SACRIFICE 05/16/91 6329-100 Location . 150 01926 wt G3ea-1e0 INHDIHVIHDUAL ANTEMORTEN 0DSERVATIONS W-- otR vex ossenvation Location aos os a n aGoorr d233 aon on aes oe G J B aur ae ass naqaaod23 aso 5 ase 1a ase ss son a sis 1a INTERN SACRIFICE 01/23/21 INTERIM SACRIFICE 01/20/91 siSLoLyn3Eg0:s0Hy0InuA s eer nex INTERIN SACRIFICE 02/14/21 TERI SacRirIcE ozr1em R--_E--hI ee astern wea RecoveRY shcRIFICE 05/17/31 INTERN SACRIFICE 02/23/31 -- Tneaomiovan-- e sacRIFice 03/2691 ween TERN sacRiFice 01/23/91 TeRninAL sacRIFice o3vassa INTERIN SACRIFICE 01/25/91 DERI SacRIFIcE o1/24rm [------------ [EN -------- . c01926 A . ERS ANUNMIBHEARL 67506 61507 es08 67509 61510 677851111 67511 61512 e513 61514 61515 61516 6e1551177 61518 61519 6e7r5s2z00 6677552211 6677552211 6677552211 1522 761552233 Hut 6329-100 INGDRIOVUIPDUA2L=AN1 TEPWPOHRTTE-W518O0BSE~RVMAALTEISONS UEEK OBSERVATION LOCATION INTERIN SACRIFICE 02/14/91 14 TERMINAL SACRIFICE 03/22/91 21 RECOVERY SACRIFICE 05/16/91 s INTERIN SACRIFICE 01/24/91 s INTERIM SACRIFICE 01/24/91 11 ABLLOOOPDEYCIACRUST NECK s INTERIM SACRIFICE 01/24/91 INTERIN SACRIFICE 02/13/91 ee RECOVERY SACRIFICE 05/17/91 s INTERIM SACRIFICE 01/24/91 s INTERIM SACRIFICE 01/24/91 21 RECOVERY SACRIFICE 05/16/91 2220 MRAELCOOCVCELRUYSISOANCRIFICE 05/17/91 14 TERMINAL SACRIFICE 03/26/91 1a TERMINAL SACRIFICE 03/26/91 224 MRAELCOOCVCELRUYSISOANCRIFICE 05/17/91 11 BALLOOOPDEYCIACRUST NECK 22 SBOLROEOSDY CRUST 3 sores BBNAAECCCKKK 1" TERMINAL SACRIFICE 03/22/91 e INTERIM SACRIFICE 02/12/91 1ea STOEFRTMINFAELCESSACRIFICE 03/26/91 162 criszy wor 629-100 INGDRIOVUIPDUA2L-AN1 TPEhNmORT1E-N51O80BSE-RVWAATLIEOSNS mNoWaDER UEEK OBSERVATION Location aasee a8 AIcNoTrEeRcIRiasacRIFICE 01/23/21 ass 5 INTERIN SACRIFICE 01/23/31 sae 1a TERNINAL SACRIFICE 03/85/91 ase INTERIM SACRIFICE 02/13/91 ese ee RECOVERY SACRIFICE 05/17/91 . ase os INTERIN SACRIFICE 1/24/31 aHasEm 3 SoABnooreoesbcyiachust wfea=p ase 2 INTERN sacaiFiee 01/1 ashe INTERN SACRIFICE 02/12/91 aaasese 338 ABILoNoTroEebRcyIiNaCrSuAsCtRIFICE 02/12/31 wean sn TERNINAL SACRIFICE 03/25/91 aasain ola aREoCrOeVcEiRaY SACRIFICE 05/16/91 as a TERMINAL SACRIFICE 03/22/91 as a TERMINAL SACRIFICE 03/22/91 ass INTERIN SACRIFICE 01/24/91 aGasseee es3os ae 3 ABBvLoooorabeDycYiaCcrruusst BLoobv crus LRAeisPcoTuorneFnFoOneRLEeLcEG ah a RECOVERY SACRIFICE 05/16/91 ase INTERIN SACRIFICE 02/14/91 ase oe INTERIN SACRIFICE 02/12/91 asa a TERMINAL SACRIFICE 03/22/91 163 01929 INGDRIOVUIPDUA2L=AN1 TEPRPORTTE-N51O80BSE-RVNAATLIEsONSHUI 6329-100 MavOaDmaE UEEK O| pscRVATION Location ase 8 G E asae aas asa 6 sss see asa a sez waaeesael:3 oss 6 m asst 0 ass ne GasEs; aed asso a sss os ass INTERIN SACRIFICE 02/13/31 RRnEaiCLsOoVceEenRLYusStAoCnRIFICE 05/16/91 reer INTERN SACRIFICE 01/28/91 INTERN SACRIFICE t/14/91 INTERN SACRIFICE 02/13/91 INTERIN SACRIFICE 02/14/91 RECOVERY SACRIFICE 05/17/91 TNBELoRorNoIDeNYeAnLcruSsAtCRIFICE 03/25/91 Back INTERN ShcRIFIcE 01/28/91 TsEoRrMINrAeLcesSACRIFICE 03/28/91 TERNINAL SACRIFICE 03/26/91 TnEoRcNcILNAuLsiSoAnCRIFICE 03/25/91 INTERIN SACRIFICE 02/13/81 INTERIN SACRIFICE 01/23/91 TERNINAL SACRIFICE 03/26/91 : 67557 e asses INTERIM INTERN SACRIFICE sacRiFice 02/14/91 o1/e3/m a sasssed33 BAILvNooTBpEoeRYciinarSuAsCtRIFICE 01/28/91 neck aso a INTERIN Sacrifice 02/12/91 164 : 0192 wi aea-100 IGNRDOIUVPIDU3AL= A1N0TEPMPORTTE-N518O0BS<ERMVAALTEISONS ANOnMBtEaR ueek OBSERVATION Location aGGssse 233 Gs ee aGss:e 64 Gas 5s3s ei2k aasees 3 ses 6 ese os HH asreEH1s HE ase 5 ase os aisoes6 asm eaze 2i0 eassts a1s asta 6 oss ass aass 32 SoaBnLLeo0spD.eYciacRust wVeeaap RECOVERY SACRIFICE 05/17/91 AIwNoTrEeRcNiaSACRIFICE 01/25/91 soBTrELeROsNOIDNYALcRuSsATCRIFICE 03/22/91 nNeEcCkK mTaEvRoRcINcALLustSoAnCRIFICE 03/25/91 INTERIN SACRIFICE 01/25/91 INTERIN SACRIFICE 01/24/91 nimEsPaILSSoITcNAcGXLIuSsion Teem RECOVERY SACRIFICE 05/16/91 INTERIN SACRIFICE 01/24/91 INTERIM SACRIFICE 01/24/91 nTaNLToEcRIcNLusSiAoCnRIFICE 02/14/91 TERMINAL SACRIFICE 03/22/91 suREoCwOuVeEnRY SACRIFICE 05/17/91 ai nREaCLOoVcEcRLYusiSoAnCRIFICE 05/17/91 INTERIM SACRIFICE 01/25/91 RECOVERY SACRIFICE 05/16/91 INTERIN SACRIFICE 01/23/91 nIaNLToEcReILNUsSTAOCNRIFICE 01/23/91 16s 01930 wi e329-100 IRUDVoIDUAL meTEevroRTTennossERvAATTILONS pWErR weex osscavarion Location asm 6 nen saenieice oars sn om mecovenr sacnterce osstam sso 8 tenn saceirice ozviamn ast stem saomirice ozs ase a wren saceieice ozvram sas nen saomieice ozsresm sen wenn sacieice ozvrem sess nem saomirice onan asses renin saoRpice ozra/m sea ren saceerce ozvresm aGsRe 8 emocceuusiRounrice saa css wm ecoveny sackiries osniesm GaseED+ wNorsEensescrice avzm aa GsEm 33 G3 soomees ee ceerr Tasiaescnk HS GGnEL1 hNeEeacnece oem asses wren sacaeice ovvewnn asm mecovenr sacuirice assem ase a wasn saceserce ozs aGsEs 13 oNeEeeRnscure oven se ie Temi sackiriee owes Gs 5 renin sacnteice ovveum 1 co193 ANUNMIBMEARL 61598 6767559999 61600 7601 6&77660022 61603 67604 67605 67606 67607 sr608 61609 61610 6t611 61612 6677661133 6614 67615 HL 6329-100 IGNRDOIUVPIDU3AL= A1N0TEPWHORTT-E5N18O0BSE~RVNAALTEISONS WEEK OBSERVATION LOCATION 1a TERMINAL SACRIFICE 03/26/91 53 aILNTOECRCILNUSSIAOCNRIFICE 01/23/91 14 TERMINAL SACRIFICE 03/26/91 6 INTERIN SACRIFICE 01/25/91 s2 HIANLTOECRICNLUSSIAOCNRIFICE 02/14/91 1a TERMINAL SACRIFICE 03/22/91 14 TERMINAL SACRIFICE 03/22/91 1a TERMINAL SACRIFICE 03/26/91 s INTERIN SACRIFICE 02/14/91 14 TERMINAL SACRIFICE 03/26/91 14 TERMINAL SACRIFICE 03/25/91 22 RECOVERY SACRIFICE 05/17/91 1a TERMINAL SACRIFICE 03/25/91 1a TERMINAL SACRIFICE 03/25/91 s INTERIN SACRIFICE 02/12/91 12a TBLEOROMDIYNALCRUSSATCRIFICE 03/22/91 NECK . INTERIM SACRIFICE 02/14/91 1a TERMINAL SACRIFICE 03/25/91 167 C01934, wi 639-100 IGNRDOIUVPIDU4AL= A30NTPEPMORRTTE5N18O0BSE-RVMAATLIESONS aNUnMiBmEaR UEEK OBSERVATION Location TE aor oe aoe aos os ea 6 a GIie] :2 eGGaeesee a93 ana TERNINAL SACRIFICE 03/25/91 INTERIN SAcRIFICE 02/13/31 TERMINAL SACRIFICE 03/22/91 INTERIN SACRIFICE 01/24/91 INTERIN SACRIFICE 01/25/91 ATELEooRroRebIcyNiAaLChSuAsCtRIFICE 03/26/91 wean nERrEaiCLsOoTVcaEcxRLlYusstSoAnCRIFICE 05/17/91 TERMINAL SACRIFICE 03/25/91 67624 14 eso eee a ers Ge a ers Gen 6 aan os aes en He aaEn z eas ae 6 TERMINAL SACRIFICE 03/26/91 INTERIN sacRIFiCE 01/25/91 RECOVERY SACRIFICE 05/16/91 INTERIN SACRIFICE 01/23/91 RECOVERY SACRIFICE 05/16/91 INTERIN SACRIFICE 02/14/31 INTERIN SACRIFICE 01/25/31 INTERIN SACRIFICE 01/23/91 INTERIN SACRIFICE 01/23/91 INTERIN SACRIFICE 01/25/31 aBICvNooTorEbeRycIinacrSuhsetRiF1EE 02/12/91 TERMINAL SACRIFICE 03/26/31 INTERIM SACRIFICE 01/25/91 RIGHT Fonerau . 168 0193% WI cae9-100 ICNRDOIUVPIDU4AL= A30NTBEPNRORTTE-R518O0BSE=RVWAATLIESONS aNnBiEmRa GEEK OBSERVATION Location aan a cass ens eas odean ad2 ees e easanre ens os 1a ees oars Geass ra eHe 32 a aend3 eso 1 a a esa eta ds se ae aGesEEs iie ese os esse RECOVERY SACRIFICE 05/16/91 INTERIN SACRIFICE 02/13/91 INTERIN SacRiFiCE 02/13/01 INTERIN SACRIFICE 01/23/91 TaEvRoKrIeNcAiLa SACRIFICE 03/22/91 INTERIM SACRIFICE 02/12/91 TSEHRARLLINAMLOVASBACLREIFTIICSE.SUE63,m8a8s7s91 INteRIn sacaiFics 02/12/91 TERMINAL SACRIFICE 03/26/81 INTERIN SACRIFICE 02/14/91 INTERIN SACRIFICE 02/14/81 INTERIN SACRIFICE 01/24/91 AEsLooonpeosoeycncaus RREACLOoVcEeRLYUs1SoAnCRIFICE 05/17/91 TERMINAL SACRIFICE 03/22/91 ARaEAuCLoOorVceEecRLiYuasiSoAnCRIFICE 05/17/91 TERNINAL SACRIFICE 03/25/91 UTuAAERRRTTN--ILLNIIAKKLEESLLAeeCssRiIioFonInCE 03/25/91 INTERIN SACRIFICE 01/24/91 INTERIN sacRiFicE 02/14/31 WIND LEFT veNTRAL Nneecxk LHEIFNTD WLiEnFoT pVEhNTRAL } 0 0193 wr 6323-100 IGNRDOIUVPIDU4AL= A30NTPEPMRORTTE5N18O0BSE-RVMAATLIESONS jrNnER vex OBSERVATION Location Gesee ess GResHt a cess cess os ceo az Gere ee GRaeeHss 4a HeGeAens a1s Gees os eHeHe 2 eGeer rsos e GGeeissesi3 Geer 1a eGHerAre es1s sINuToEcRLIeMn SACRIFICE 02/14/91 aTcNoTrEReIcNiaSACRIFICE 02/12/91 TERMINAL SACRIFICE 03/26/31 INTERIN SACRIFICE 01/24/31 RECOVERY SACRIFICE 05/17/91 INTERIN SACRIFICE 02/12/91 INTERIN SACRIFICE 02/13/91 sCToHNuRTnEORwNIrONiDnAgGSARCYROIRFRIHCEEA 01/23/91 SsRHEoACrLOeLVcEiRMaYOVASBALCERIFTIICSESUE05/W1A6S/S91 INTERIM SACRIFICE 01/23/91 RmEaCLOoVcEeRLYustSoAnCRIFICE 05/17/91 AIoNrTeEcRiNaSACRIFICE 02/13/91 RmTaAELIRoNMcOIcRNLARLUHSEIRSOANCRIFICE 03/22/91 TERMINAL SACRIFICE 03/22/91 SaRHLEAoCLrOLeVcEiRMaYOVASBALCERIFTIICSESUE05,M1AS6S091 Lert HID Pau RRiicuur eevvee IND RIGHT VENTRAL WIND RIGHT VENTRAL mn 0193F" wt 6389-100 IGNRDOIUVPIOU5AL= A1N00TEMPOPRRTETN51O8B0SER-VAnTALIEOSNS aWOnNDnEaR GEEK OBSERVATION Location aganad3 eaeae e HfEene4 aad area qaees 8a feGereeee 3riez fH daaeeHHaf fGGeeeee esa ffeaee Eae en es a er 1a ceo a EeHeH 2 GGeeseees e: eer a mTEaRLMoIcNeALLusiSoAnCRIFICE 03/25/91 TmEaRLMoIcNeALLusiSoAnCRIFICE 03/25/91 BBaLvLooOorObeDvcYiaCCrruusstt TERRINAL SACRIFICE 03/26/91 RECOVERY SACRIFICE 05/16/91 aIoNrTeEcRiNaSACRIFICE 01/24/91 SusSoLuoiootLoiernncrust SSBTouigoeeLrLEnnot use mHTUihNsiCsHiEnD POSTURE RNEeCcOrVoErRiYc SACRIFICE 05/17/91 TERMINAL SACRIFICE 03/26/91 RECOVERY SACRIFICE 05/16/91 TERMINAL SACRIFICE 03/22/91 INTERIN SACRIFICE 0e/1e/91 aIoNrTeEcRiNaSACRIFICE 01/25/91 BaILvNooTGrEoeRYcIiNaSSRuAsCtRIFICE 01/23/91 RECOVERY SACRIFICE 05/16/91 RreiacpuT roreray RSTIoaGHiHTHFINoDrePrAuuS 3BT0OaTTiHH HFoInNgDeLaeucss TIP oF TALL a nee . m 0193% wat 389-100 IGNDRIOVUIPDSUAL- A1N00TEVPPONRTETR-5O18B0SER~VAMTALIEOSNS MavNiGnEaRL VEEK OBSERVATION Location eGisn 9a eGweeeesss 222 [. eee 1a EU cGGrrriieseees 1100 GGRrrHiieEss 110s R oesH.3 ens Greesnt viee wz 5 sess r6cre6r5eeess:ar2 cress re cess Gera cess 6 Gene RT) nRaELCoOcVcELRuYsiSoAnCRIFICE 05/17/91 aS8ov0noe0rs0e0ciacaus MORIBUND SACRIFICE 01/16/91 TERNINAL SACRIFICE 03/22/91 INTERIN SACRIFICE 01/25/91 aHRAciLonOrCeCcLiUaS ION FSTEEoURrMIGRNFAeLcNeosSFAeCcReIsFICE 03/26/91 cIrNoToEkReNn SAGRIFICE 01/23/91 INTERIN SACRIFICE 01/23/91 nTEaRLRoIcNcALLusiSoAnCRIFICE 03/25/91 INTERIN SACRIFICE 01/24/91 INTERIN SACRIFICE 01/24/91 a5RLcE0oC0rODeVYcEiRaTCRuSsATCRIFICE 05/16/91 TERNINAL SACRIFICE 03/22/91 INTERIM SACRIFICE 01/24/91 TERNINAL SACRIFICE 03/26/91 INTERIN SACRIFICE 01/25/91 INTERIN SACRIFICE 02/14/91 TERNINAL SACRIFICE 03/25/91 NNeeee Tie oF TAIL Lert ForeLe . 2 0193F wt 329-100 IGNRDOIUVPIDU5AL= A1N00TEWPOPRRTETN-51O8B0SER~VAWTAILEOSNS aNOnRiBmEaR week OBSERVATION Location ea are ce rss eros ee arse eHnEeH a eGnrerr 2oe eH(reHres 1 ares a aren ame anew eamnas a Gree ems 5 earnee o1e m ar ne f mes aanmss 83 emz0 1 RECOVERY SACRIFICE 05/16/91 INTERIM SACRIFICE 02/13/91 INTERIM SACRIFICE 02/14/91 RecoveRY SACRIFICE 05/17/91 INTERIM SACRIFICE 02/13/91 aRLEoCpOeVcEiRaY sacRIFICE 05/17/91 AILNoTrEeRcIiNaSACRIFICE 02/12/91 aBILLNoTorEoeRycIMtacrSuAsCtRIFICE 02/13/91 Neck INTERIM SACRIFICE 02/12/91 INTERIN SACRIFICE 02/14/91 INTERN SACRIFICE 02/14/91 TERMINAL SACRIFICE 03/26/91 aILNoTrEeRcIiNaSACRIFICE 01/25/91 TERMINAL SACRIFICE 03/25/91 INTERIM SACRIFICE 01/24/91 aTEoRrMeIcNiAaL SACRIFICE 03/22/91 aILNoTrEeRcIiNaSACRIFICE 01/23/91 INTERIM SACRIFICE 02/14/91 mINaTLEoRcIcnLsSTAOCNRIFICE 02/12/91 TERMINAL SACRIFICE 03/22/91 . mn 01939 wi 630-100 ICNDoIuVrIDUSA'LS A1N0TEPOoRmTETNosOegBeSE=RVMAATLIEOSNS aNWiRn ucex osseRvaTion Location ame oGrd es res ae ree ans 5 INTERIN SAGRiFIGE 02/13/91 nTaNLToEcReILRusSiACoRnIFICE 02/18/91 Recovery sacaiFice 05/17/91 INTERN sackiFice 02/13/91 INtERIN SacaiFice 01/23/91 n 0198 wr eaes-100 INGDRIOVUIPDUA6L-AN6TBEPMNORTTE-M518O0BSE-RVAALTEISONS aNonMiEmEaR vee osseRvATION Location ares arate ares oe amass ane ne ame ane 1 ams anes ans s ame 1a are ans a ee Gao 1a ars res rae Grae 1 ress r raeesae arr a cra a INTERIM SACRIFICE 01/23/91 INTERIN SACRIFICE 01/25/91 INTERIN SACRIFICE 02/13/91 INTERIN SACRIFICE 02/14/91 TERMINAL SACRIFICE 03/25/91 INTERIM SACRIFICE 02/18/91 TERMINAL SACRIFICE 03/26/91 INTERIN SACRIFICE 01/23/91 INTERIN SACRIFICE 02/12/91 INTERIN SACRIFICE 01/24/91 TERNINAL SACRIFICE 03/26/91 INTERIN SACRIFICE 02/12/91 TERMINAL SACRIFICE 03/25/91 INTERIN SACRIFICE 02/14/91 TERMINAL SACRIFICE 03/22/91 INTERIN SACRIFICE 01/23/91 INTERIM SACRIFICE 01/24/91 INTERIM SACRIFICE 02/13/91 TERMINAL SACRIFICE 03/26/91 INTERIN SACRIFICE 01/24/91 suToELRLIENnAL SACRIFICE 03/25/91 aL TERMINAL SACRIFICE 03/26/91 TERMINAL SACRIFICE 03/22/91 us 01940 wt 6329-100 INCDIhVoIDrUoAL AN5TPEPNAORTTE5N10O0BSE=RVAALTEISONS WaUnMBiEaR ue osservaTION LocaTion Gre ames ams ame oe ae ms e arse ie ess ia ame ars ame oe ames are ie ans eres aaarse Gree s aRirse aBrAeI 1 rer cree oe ares os ams TERNINAL SACRIFICE 03/28/91 INTERIN SACRIFICE 02/13/91 INTERIN SACRIFICE 01/25/91 INTERIM SACRIFICE 02/14/91 ICNHTREORMIONDACSRAYCORRIRFHIECAE 02/14/91 TERNINAL SACRIFICE 03/25/91 TERMINAL SACRIFICE 03/22/91 TERNINAL SACRIFICE 03/26/91 INTERIN SACRIFICE 01/25/91 INTERIN SACRIFICE 02/14/91 INTERIN SACRIFICE 01/24/91 TERMINAL SAGRIFICE 03/22/91 INTERIN SACRIFICE 01/25/91 INTERIM SACRIFICE 01/23/91 aTvNoTrEeRcIina`sacntFice 02/13/91 INTERIN SACRIFICE 01/25/91 nTaNLToEcRIcRLuSsAtCoRnIFICE 02/13/91 mIaNcToEcReNLusSiAoCnRIFICE 02/12/91 TERNINAL SACRIFICE 03/25/91 INTERIN SACRIFICE 02/1/91 INTERIN SacRiFIcE 01/25/91 INTERIM SACRIFICE 01/25/91 niet eve ws 0194f wo IEEEEh sue ome a = T rr HORDES EM ELM mE gE Homi Ei on a a wh wt wn we dd E EOEEEDEE ED E E EDE EEL E BEiDEw E aDdo EaBeEBEoamEyly mi wEsEmEe 0 ah 0wm0 aEa bd TadEo sEeiSs wd Hh ORm DE og E E EOE E REE Ea ppm B EmSh E omy Yeg elTywel wleeen HHOEREDEEA EEEE gE Emi ED ERE EOET aHEn]C E E]OTS eh od e0 e a a mel a se R doomR BLEER D SE DE E TImONSLoer omy DE Aosea sen al dO EEE EEE ss se we ws wn o HE BML BE EE on Lo 0 DED EE Rm $SB wom "+ easAxia omd Em OE LL whoa e's wl wom ad Bos ma 1s FERR2 ESn see ome oor a 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8 EEE TET - | HEE Sa Sea ESE wee ars eel ees as ee 3 1 BER SEEN, So vse a in . 1 io 5 HHL sd wl wh od wd sl wl wl HH wie sel ae se smeom sen i wi wis wi Py wi wie wn i san -- -2i + +ota anal 5 : : : : : = i SHEE SHESEEBoe vse ome I TT dom ED ED ED EE D000 DL Lh wh wh wh we 8g3e = & BE a ym 12 BRR BREATHE, Uh vos100 nie 32 8i] < Boros rrrsa ann " esara b|32 s. 2 o a or Bows watsra . i $Bg5 Horrrrrsma stcr oi reoa b[32 s3 8 FE a tim g32 a2 f w---- 2 rrrssTsetrrrr esa P22O hae HB rrr ms v s otssaa 22 r2E 8 PEI RI rae one = hea Lewaa WORDED ERR ee mm wa ww un HORE io iH EHD EEE moms my moon oe mn om en eae Hs : Wom m mm ew DE i HEME EEA en ee wy 00AFEE dom WEEE EE ome eh mew wl HOE ED ROBE EE wr whom od a om Hom fi HOD ORDOST wh who) on . i 83g 5 a a Ta we aes ae om aed wet es e's a's ase REHEAT vse on Be ea aw Hows wom om omy ow HE ee ed el a wi : doopoi iid 2o Ew- we wh wl wi wh &&g 3 BO HEED FRIES 50 se ann ey RED Dm mm wr 2g EREso Jr---- &3 HETIL 507 se mn S EE ua ey 3 ER or re I] ~t BOS UTES 0% sue one ey HEH BMH MLD Wn a BW wt wh wt om wn HORE EDEL Gy wh LL LL LL HOHE HOWE ELE OB EDA ow mom EE omgomd EER ond a mow uno wh ED gE md EDEDE ED 0 Ds i i HEED uo ed ml ed el wl wed BEE m md dE Boman AEE Te ED Ll Nn 0 WL Com BPEIERIEEIE LL LLL 3 ERA ro wars on secs bE B Er -- WRB 0 sue J-- Bl wh hh wl uh al Homo omd omow BE wh wd mi ws om wm BE ol le ie hu iHE A mie whe wl A wl 3 oz 2 BeWe o Th r aa Tm PRETTY 90M suv ron HBE OBBEEALBa EABe SEER ee Th al S ahoME EE me mE COTY TD Tr Tr TE TE 8g - URAL RSAIISY 80M 5100 100 EE ewa py 3 2 5 NC SURE $0se om Beyo Bo EERE d gHoo EEREE EG EmE EELEEEELGTLn LBnD TY T om E a Ewh TTT I R mwhe Em om e B noo EBEEH EEOEEE LG BoE EE Be B Wh Eah wh0 wh10 wh1 wh1pwh TET ERT omen wR EOE EE a RUE BDOREED Lorn wow wd oud pb mom oul BEOEBEBEED REDEDBL Gh ah wT mh ed wl ml el eh LL wh wEoTe me Q BoTo. R romwieonsre mmm SITIES sre ann BE Tn a ae pa ms ee ms Hwou owhaowwhdom om omwhyomyoh oe BEomnomnomoan wom oh Hl woh sale wie wie wh wn SEE rmwie re 58 Go ERECTSY 0M su00 rr Er ae yy HOHE RD RDE Ea ae HaoOnD wEERE EED EEEERRmEmRm E REeEe 2 TRI rom aro an ricco =I] TLRS 0ore -- Ee aaaaew J 32: & ASTI 0 se wn BOs ey E BOREa R md m mi m ee e ennme. IH HOE ED BEE RDB E gn my om omy WmmE ows ow em el wlomp me me mom dof Rem wiow wh wow wh HgaEMmOEeE E EEOMEE EERR Dan oRmE Ey ow vem foe ne ee wO h mhEowl wm d wl s dO EE a Ban BED mom ome own H HoOO ED EoEmRmRn OBREaSE LoE RmE EOEhRmeDmEgt Ranwe , mm we wi wh wh 23 = & ARETE 0M 100 io TA c ------ I 55 <4 STIS 0 oe os Ei --_-- ae, ey domo EE a a ND HOE EE EE Ems ee Bw . 2Bz~ 33 AUBREY 10 seo Bs aa wowmyo wi ernie 32 4S == EH rrr Pfrras aoa mim - Le otmes te. e2S 2 oom = rrrrca msi tis o3g5o. : oe "Yo EB rrr Es rarrvwaa g S . 2 EE omcoin a3 B Ee o Gy [I p---- EE Eaw mL 32 2 F ERi fr mcm BE PI r f rr rr ss re ao o22, & HMI 6329-100 APPENDIX C Individual Clinical Chemistry Values 221 co1986 ann i 3 Wzs n= <r [esis "eos Lote gi # kl He `voskor uit: ome :3s ~ :- 32 28 gm "~ I J aE o22Bg E&O 8 go 3 ow Ha gg an 3 go goo FY gg : "w o3 B N 3 8 % |. ha i 32- 38 am : Eid } 222 @ Hs @ we Ee git i ai 1