Document 2jo5Qm9wMJQE1yprLjvgNMw7r

AR226-3573 PERFLUOROOCTANESULFONYL FLUORIDE (POSF; T-7661.4) TOXICITY STUDY BY INHALATION ADMINISTRATION TO CD RATS FOR 13 WEEKS FOLLOWED BY A 4 WEEK RECOVERY PERIOD Volume 1 MIN 313/023622 PERFLUOROOCTANESULFONYL FLUORIDE (POSF; T-7661.4) TOXICITY STUDY BY INHALATION ADMINISTRATION TO CD RATS FOR 13 WEEKS FOLLOWED BY A 4 WEEK RECOVERY PERIOD Volume 1 Sponsor BMU33SMMtuSNPiAlaCCd5.uieo5nln,r1gpt3eo23rr,2-a30t2e-22TE0o,-0x2ic,ology, Research Laboratory HAHPEWCENaluuocm2nnGoo8ttbnliiLlnnrb4eAigguHydddNrgSRyooeD,,nnos,.haLdiri,efe, Sciences Ltd., Report issued: 28 September 2005 Page 1 of 740 MIN 313/023622 CONTENTS Page CONTENTS......................................................................................................................................... 2 COMPLIANCE WITH GOOD LABORATORY PRACTICE...................................................... 4 QUALITY ASSURANCE STATEMENT....................................................................................... 5 CONTRIBUTING SCIENTISTS...................................................................................................... 6 SUMMARY......................................................................................................................................... 7 INTRODUCTION.............................................................................................................................. 9 EXPERIMENTAL PROCEDURE.................................................................................................... NAPDTQSSAETEENAURUSCTITAMTIDHRAALYOASOILTTUPLLSRYOSBOCMEBYSAHGAATSSAEYAETNSDN.RMNU.A.UD.VCR.EG.L.HAEAN.EE..ITNAM.TS.A.ICN..TO.E.N..EOD..NN..D...LA.TF.S...SO.N.O......T....G.D.R......R....Y..M...A...U...........UR...C..........C..L...T..........HA..U.............IT...R.....V.......I..E...O...I.......N........N..........G...........................P.................R...................O.......................C.....................E..................D.....................U.......................R....................E....................S................................................................................................................................................................................................................................................................................................................................................................................................... 11 2221111122165392 RESULTS............................................................................................................................................ 27 DISCUSSION...................................................................................................................................... 35 REFERENCES.................................................................................................................................... 36 FIGURES 1. Bodyweights - group mean values.......................................................................................... 37 :2 : MIN 313/023622 TABLES Page 24356781........ MFBBHUMOoioraraioiogcedcncdarmyrahonowlcaesyswocmtecsoonioielgispsosiphugitg-icrtmhcysygtppprs---aoat-gtigguthorhgrrpoonooorulmouulo-opuppgeggpmaymmryonme-eeu-avaaegpgnnnaarrmonlvovvuuuaevaaepplaallsunuudl.de.ueei.vsi.sesss..at....tsr....lr.....iui.....b.b....e.....u....u.s......t....t......ii......o.o............nn...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................... 4457368810208637 APPENDICES 24356798111.........01.. ADFBHBUIpWCnHoioebraadoeioledisnielclvdovmyyakhpaliwllcudaelrpyyuoomttueosoeelnipaisilgisssflhtosoh-eutfypgr-drrtomgsyasyaoirianttpsc-hin-t-deotaeoiiiiiwlrnnovnnlomodeniddbefdgixiiiiisv-unvvngiaeciaaiihdimrdddanllvtiuluusdniavunaaafigt-arvlaiillsionltiivn.vvuindnd.oa.eaaedu.sin.l.llnsia..uuu-v...lg-...eeei.i..vs.d.i.nsss...n..au..d.......d.....l.a.i......u.....iv.l......v...e....i..v......id..s.....d..a.....u..........u.l.......a.....u....a.....l........e..lf.............i.s....f....n.........i............dn...................id.............n.........i..........n.g....................gs.....................s........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................ 222211111119910033572131622580888 ADMINISTRATION OF POSF BY INHALATION TO RATS...................................................... 298 MSCICARNONAINNGAELLYESCIST.R...O...N....M....I.C...R...O...S..C...O...P...E...E...X...A...M....I.N...A...T...I.O...N....A...N...D.....X...-.R...A...Y.................................... 369 ANALYTICAL PHASE REPORT....................................................................................................... 518 HEYUENTRIENSGEDAORNCHRECSEENATRRCEHGCLPENCTORMEPGLLIAPNCCOEMSPTLAIATNEMCEENSTTAS.T..E...M....E...N...T..S....................................................... 773358 Volume 1................................................................................................................................................. 1 Volume 2................................................................................................................................................. 366 :3: MIN 313/023622 COMPLIANCE WITH GOOD LABORATORY PRACTICE PERFLUOROOCTANESULFONYL FLUORIDE (POSF; T-7661.4) TOXICITY STUDY BY INHALATION ADMINISTRATION TO CD RATS FOR 13 WEEKS FOLLOWED BY A 4 WEEK RECOVERY PERIOD TPrhaectsitcuedsytadnedsacrrdibseadndinItchoisnsriedpeorrtthweadsatcaongdenuecrteadtedintocobme pvlailaindc:e with the following Good Laboratory TSthaetuUtoKryGInosotdruLmaebnotr2at0o0r4yNPora.c9ti9c4e. Regulations 1999 (Statutory Instrument No 3106) as amended by OECD Principles of Good Laboratory Practice (as revised in 1997), ENV/MC/CHEM(98)17. EECC CCoommmmiissssiioonn DDiirreeccttiivvee 21090949//1101//EECC ooff 811MFaerbcrhua1r9y9290(0O4ff(iOcifafilcJioalurJnoaulrnNaol.NLo.7L7/85)0,/4as4)a.mended by TSthaetsees oprfiAncmipelreiscaoafnGdoJoadpaLnaboonrtahtoerbyaPsirsacotficientaerregoavcecrenpmteednbtayl tahgerereemguelnattso.ry authorities of the United Adunraetxiopniroyfdthateesftoudryth. e test substance was not given. The material was assumed to be stable for the tGShcLeaPnstnumidnoygn. iEtolercintrgonprMogircarmosmcoe.pyNaondclXai-mrayofacnoamlypsilsiawncaes wcoitnhdGucLtePdisbymaadfaeciinlitryeswphecicthofisthneosteppahrtaosefsthoef HTSteuurndetnyincDegdiJro.encKtoLenri,fney,SBci.eSncc.e(sHLotnds..), Date 4 MIN 313/023622 QUALITY ASSURANCE STATEMENT PERFLUOROOCTANESULFONYL FLUORIDE (POSF; T-7661.4) TOXICITY STUDY BY INHALATION ADMINISTRATION TO CD RATS FOR 13 WEEKS FOLLOWED BY A 4 WEEK RECOVERY PERIOD The following inspections and audits have been carried out in relation to this:study: Study Phase Date of Inspection Date of Reporting Protocol Audit 10 December 2001 11 December 2001 NEaACCFSTaStnrttxellemtueuaiimspcnnsdldtoroyhiioyoscIcyssstppaauipepBsulhlsrmr.hyreeaessieriipnscrggeeaaeeonndnrnssasdctIta((rionmpwooglsolnlepepesanelcetink-etncdidrlgtoyaoindto)siienos)fnspoorosiftSioEtenMst 222000 DDDeeeccceeemmmbbbeeerrr 222000000111 2200184DDJJaeeanccnueeuammarrybbyee2rr200220000200211 21 March 2002 222000 DDDeeeccceeemmmbbbeeerrr 222000000111 2200184DDJJaeeanccnueeummaarrbbyyee2rr200220000202012 26 March 2002 Report Audit 9 1J9un2Je2ul2Sy0ea0pn4tde-m225b2eJruJ2uly0n0e250200504 22 22S45epJJtuuenlmyeb22e00r00254005 PDriroetcotcoorlaAndudCiot:mApannyauMdiatnoagfetmheenptraostoicnodlicfaotredthaibsosvteu.dy was conducted and reported to the Study SSttuuddyyDbiaresecdtorinasnpdeCctoiomnpsa:nIynMspaenctaigoenms eonft pahsaisnedsicoatfetdhiasbosvtued. y were conducted and reported to the Prporruootmcinepestslyabnrdaepseroedrpteeidntisttpioveeacptpiporrnoocsp:eridaAuterteCsoroemambppoalunotyyetMhdeaontnaimgteehmistehnitsyt.psetuodyf swtuadsyinweprreogcraersrsieidnsopuetc.tioTnhseosef owthereer RcoenpdourctteAduadnidt:reTphoisrterdeptoortthheaSstbuedeynDaiuredcitteodr abnydtCheomQpuaanlyityMAanssaugreamnceentDaespianrdtimcaetnetd. aTbohvise.audit was rTehseultmsetothroedfsle, cptrtohceedrauwredsaatan.d observations were found to be accurately described and the reported tDIhneevtealsieltsvigeoalftoothrf'esPQrOeupSaoFlri,ttyiPnAFcslOusSudreadannacdseaPinnFsaOpdeAdcetiniondnuslmiavnetdor atahunidsditmsseaprienurmtraeipnsoianrmtg.ptloesthaerAe nparleysteicnateldPhiansethdeetePrrminicniipnagl DHTGreuraopncuatyiprntSmgMcdeaaoinnjnftaeoLg, feiFfrQ.e,RuS.aQclii.etAyn.cA,esssLurtda.nce. 5: CONTRIBUTING SCIENTISTS MIN 313/023622 STUDY MANAGEMENT TSteurdenycDeiJr.ecKtoern.ny, B.Sc. (Hons.), RSehniaionrnoSntuDdyavSiuesp,eBrv.iSsco.r.(Hons.), DSeenreiokrWTo. xCiocoolmobgsis,tB. .Sc., MSc., AEROSOL TECHNOLOGY AND ANALYSIS ISaenctSio. nGHilkeiasdo,nA, Mero.Aso.,lPThe.cDh.n, ology and Analysis. CLINICAL PATHOLOGY PHC.eeTnadtrraaovLifsaC,bBesn.CStrclai.ln,iLMcaa.blSoRcr.ea,steoaryrchS.ervices and Clinical Analytical Service Manager, PATHOLOGY DSairmecuteolrMocfCPaotrhmoilcokg,yM. .V.B., M.R.C.V.S., Ph.D., F.R.C.Path., STATISTICS HGeraahda,mDeFp.aHrtemaleenyt,oBf.SStca.ti(sHtiocsn.s.), M.Sc., A.R.C.S., BIOANALYSIS REU3S0txiSac5yAth8ega.eRCrndeoRsAlleee.asgrGeeca,rhraPczDhAzr,iinv1ie6, ,800, :6: SUMMARY MIN 313/023622 w2Tagfdefuoad6rohhorlc,mseltiuhoehc1ipdswhen0gysr4iifrs5snooo5ttagerrumfnamm4ptttdaheiiawloncew2elnee9setm1seo9wr3akexanaapwslinedcspaoedlmapael5nosnkol5sycbfdstee.aeyfsmetnteseexvTtmeadnipoeadlaolenlfaulssoeesommumvsprfreeaeeaewtrl.rlhcefeeaeoograrvrpretnaoeee1tdrusars3yitpltolrewsoedgwnucecrbaoeeoefsetrkiufevetmspad1e.ns3adaacalAewncesPr,irOeimssafPeiaiStmakOctsFelseisSil,dlnlabFi.fatryo,GenlylTdtlrsoaoonhcnwwuoeoCipumenerrsrtldse:aetCmo1ilbtsn-Dauya4lltityloenawodiwi4ne(nGSCrgehwerDdoao5ee)lnuateIxtmpoGtkrpiooaSorr1llneesegcBecaarodonaRotvvndufeeedorpxrr4aryp5trfs1oeoop3fcsnbreeuelwyrmyrifiveooeaieauendlldenkrh.edsvaraw,Tleaiawraleth.tssefiertokeroeiAnenesrf Duruinrianlygstihs,eosrtguadny,wceliignhict,aml caocnrodsictioopni,cbaonddymweicigrohstc, ofpoiocdpcaothnosluomgyptiionnv,eshtiageamtiaotnoslowgeyr,ebulonoddertcahkeemn.istry, Principal findings are summarised below: Results Mortality and clinical signs rTehceorveerwyearneimnoaltsredautrminegntt-hreel4atwedeeekffreecctosvdeuryrinpegritohde. 13 weeks of the treatment period or in any of the Bodyweight Following 13 weeks of treatment with POSF there was a dose-related reduction in bodyweight gain. Food consumption A4sigwnreeiefdikcusacnoticfoerneactiotnavienfroeydofdfeomrcaomlneaslufeomso,pdcticooomnnpswuarmaesdptwisoeinethnwCaisnonsttGirlorlolruefpodlulco4ewd(iHningigtr1he3adwteoedseegk)rsoauonpfismt.reaalstm, ewnitt.h Fsotalltoiswtiicnagl Haematology There were no findings considered to be of toxicological importance. Blood chemistry Amlakleaslinceomphpoarsepdhawtaitshe CleovnetlrsolwaenrderheimghaienrefdohrigGhreorupfol3lo(wInitnegrm4ewdeiaetkesdoofsree)coavnedryG. roup 4 (High dose) Arelmanaiinneedahmiginhoe-rtrfaonlslofewrainsge 4lewveeleskws eorferehcigovheerryi.n all treated male groups compared with Control, and Cfohlloolwesitnegro4l wleeveeklss woferreecloovwereyr.in all treated male groups compared with Control and remained lower Cforleloatwinininge4awnedektsrigolfyrceecroidveeryletvheelslevweelsrewerereduccoemdpaforarblaellwtirtehaCteodntrgorlo.ups compared with Control, :7: MIN 313/023622 Urinalysis There were no findings considered to be of toxicological importance. Organ weights A4gsdstiroagbwostnsueieosip)eftl.isikucc.taIaernnlelTtcylslioyhavvsteeegierglrrldenyiwitaifeftepfieeicrergraarethtinhsnottsacdlaynefwtsthcheeoerwirgne4erhterrewgoecrolreevsfewaotkeaterrestiyirgGsehtxatirthcnopsaa.uiomnlpslyuacr3loe'ssni(agItltrnniovttiheflesirercaidwHnnoeitsgbiegwho)hthdhtmseo,nassweleexahsldeeesjvaunensoldatfetdhditjnehuefslbotieovrIdnethbtrefoowrsdmreeyxbiewgeodeshdiiatygsotwehfwte.GaeingrredohFutos,Hptlarlioetg4imwsht(iiaHncdiangoilgeslhydea Lsllasuutinuagnnintnmggigsifaataiilnaccnsndaadndlabltbyflrbtryoeorsnrohingcnic4nghchihihfiewiiwcwrewaeteenihegiktagilhsgnyhthstochstiosifnginnhe(mtarxeofbaprelslssmteoh.olaHauulnrteieegschoaawnndtetdortrsohebelesosrdiaaHmytfsitwigelrraheerim1g3dthaooitwsnceaeeo,dednjklutssurtsonatoeltgsfidse)taaixfcniptandeolrlsHybu4rirsgoewihn.gecnAdehifkoifisscteewaroner4ftailgyrtwsehhcteosoiegfvkhwesbereooryrt.fethhreasIscnnteaoxctvSeiosesantrtityewcrlaoltelihlrltsyeee, mKnsdatcoiaiafcdtfldoieensiursefteinfycwnetaercweelderlnesyeficgoisenshrtsaittfgtsiheinn,semitwkfihaicihclidaegaenlshnlne.yetylaryAsdwibgfjouhetnedisiiggrtfyeihh4wcdteaweranfiofegtttlreehhykrbtagson4arddoewyjcfauweotrseeenetrkcetirtosgdhovholaketsnfi,rdyeicannxoftepthnmyeoetrsrawboule1oelrse3id.rg.yahTtwwtssheefeenirgrkooehsmtetwdoatehdfirenjeueImnsxntopeateodlhersimskus.itredoeIdnp.nieaaytstheaTwothealeolenlirgidgetyheHtfrswiiagnoethdsrfeitHndhgoenigssroeehwwwdshuoeeiccsrrhheee Macroscopic pathology Ewr1e3nictlowhavreengeroekynms.eecnointmotphfaetrheCdeowlnivtirteohrlnwmoanaseleoinbrasttehsrevaeCnddoniintnro43l//55ramtms.aalleeThrraaisttssfitanrneddainte2gd/5wwfaeistmhnao3lte0a0rpapptsparmterenfatotferodl4lwowwiteihenkg3s040cwopmepempkasrfeoodrf Microscopic pathology The following findings were related to the administration of 300 ppm of the compound: rnrllsluieaeeovrccnxtyeoogaernvvbssxele-wy-rr-cyyifnetaohionenfactffimrnfertieohcclymostoeeibsmasdaeull,peolvfalsfeieprnotvredhloeaienrmnreptgrciamnasotleoavinnccceatyrrborytotepciitlehnahhnagmytgserpee,iaxleslwo/eresbtssire.tuophalpntaanhdrloychteoheevmixpcitdakpeteelnoenndctcieiynentrggeeo/csftocporaveigtcetthmeoryerveeeinmdnrtyifadeiilznnvmoemanoflaeleaalmslreaasmrleeaasanc,drwoawipntihhdthamgiiennasccleooismmn mppbllooeertttheee rTeexhcteoenvadedrimnygianttiosthtretahsteeiodmnoiosdefzl3oe0nvaepllpsa.mreaoro1r0c0epnptrmilowbualsarashseopcaiatotecdytwe ihthypceernttrroiplohbyulianr mheapleasto, cwytiethhiynpceormtropplehtye Conclusion Teoxrhteceenanddtirmnilgoinbtioustltraharethiomenpiadtzooofcny3at0el aphrpyempaerootrrrocp1eh0n0ytriiplnopbmmualwlaeras,hsewapisatshtoocicniyacttoeemdhpywlpeiettehrtrrcoeecpnohtvyrieleroyxbtuaetlnatdrhienhsgeeptdaotootshceyelteemviehdlyszp.oenratrloaprheya It was not possible to identify a no effect level in this study. :8: INTRODUCTION MIN 313/023622 Objective Tfaalnnohydeur4eiodfafbeenjecd(ctPsdtOiovwSseaeFsdo),affoswtsrheh4isessnwesdeateuddkdmusy.riinwnigsatsearte4od-wbaesyseekssnsroeucthotevoensrlyyystpienemrhiiaoclda.ttoioxSniacttoeplloriatteetsnrtafiotasrl wo13efrwpeeearelflklousco.artoReodeccttaoonvGeesrruyoluffoprnosmy1l Regulatory compliance The study was designed to meet the requirements of: EGuuriodpeeliannesEfcoorntohme iTceCstoinmgmoufnCithieesm. icals - 413 TG(ShoceoiedsnttuLidfaiybcowPrraaotsocrecydounPrderuascc)ttAeicdcetinS19taa8cn6cd.oarrddasn, caenwd itthhethaeppreliqcuabirleemseencttsioonfs coufrrtehnet, UinntietrendatKioinnagldlyomrecAonginmisaelds Test system uTanshededtrhbaeetcwraeauqssueicrhoeomfstehennethafsiosrtthoaerircoteadsletcnsotpnsetpcreoieclsidebasetbacyaauvresaegiluaolbfaltieotsriynactahcgeiespntlcaaibneocser.aTatoshreya.Cprrel:dCiDctor (oSfDto)IxGicScBhRangsteraiinnmwaans Route of administration Texhpeosiunrhea.lation route of administration was chosen to simulate the conditions of potential human Treatment groups and dosages tT(SaHphrgoueenntdstioocnrosgandwgcoeeinstnhtLuraisrfteeeifdoeSnricenoinefctn3hec0ies0tsospRtpupemdrpeyovwri(tho0Neu,rsue3m0wtr,baoen1rrks0:i0eMwnatIintNchdli3nt31hi0c2i0as/l0p1cepof4fmm2e7c)p2tos)wu.wenerdIenreptssheeearlefetnocs.rttemuddeydinrianctos ntwhjueesnreectieloaxnbpoowrsaeittdohrtiotehsea. Study location The test system was maintained at the following laboratory: AEHHWHPCENlauuuocm2nnnGoo8tttbnliLiilnnnrb4eAiggguHyddddNrgSRyoooeD,,nnnos.,haLRdirie,efse,eaSrccihenCceenstLretd, ., Histology was performed at: IEHEESPNyuyu2feenG3f,otRLi7lnkeAPgs,XdNeao,Drnc.hLiCfeenStcreie,nces Ltd., :9: Scanning electronic microscopy and X-ray analysis was performed at: PUDPPlLlrnyya4immkv8eeooAruuCstAtihihtry.,cEuolsef,cPtlryomnoMutihcr,oscope Unit, The bioanalytical phase was performed at: EU3S0txSa5yAt8eg.eRCneoRslleeeasgreeca,hrPcDAhr,iv1e6,801, MIN 313/023622 10 : EXPERIMENTAL PROCEDURE MIN 313/023622 STUDY SCHEDULE AND STRUCTURE Duration of treatment Tco11o33bhmsewceopretvnleeeassktettesico.dsunutiAsnibvnse1twiamdnewaarceeylese,, kardPessuOcsrioaigSnnrnFdgdee, dwdfwothoraaicsttshhaaeattdpiermmplelcrieitonoetpvirsreertiaaerayttrtmseepdehainanftposteerecrrovci6noaotldmhisn.opuouleTferdsthe4uedapwaddteofuaeuyrktra,hstth.ei5oednTrdahfayoeoyupfsrnriwteaorceerrwaeottokepmessnkeywenciotptrvhorioeopsrcuseytrade,trupaperonaeerdtrstmieosdwedenreitraoa.eslf Time schedule (SPturodtyocinoiltisaitgionned: by Study Dire Experimental start date: Treatment commenced: NecropMRSsaeyatceiconlolviSmetetrpuySldetSyutetdudyd:y Experimental completion date: Study completion: 6 December 2001 6 December 2001 20 December 2001 211159 MAJapnaruriclahr2y02020200022 29 October 2002 28 September 2005 Identity of treatment groups The study consisted of one Control and three treated groups of rats, identified as follows: Group 1 2 3 4 Treatment Control PPOOSSFF POSF Target exposure level (pp0m) 30 100 300 Main study (13 weeks) No. of animals Animal numbers Cage numbers M5ale Fem5ale M1a-5le F2e1m-2a5le Ma1le Fem5ale 5 5 6-10 26-30 2 6 5 5 11-15 31-35 3 7 5 5 16-20 36-40 4 8 11 : MIN 313/023622 Group Treatment Target exposure level 1 Control (pp0m) 2 POSF 30 34 PPOOSSFF 100 300 Group Treatment Target exposure 1 Control (plepvmel) 0 4 POSF 300 Recovery phase (13 weeks + 4 weeks recovery) No. of animals Animal numbers Cage numbers Male Female Male Female Male Female 5 5 41-45 61-65 9 13 5 5 46-50 66-70 10 14 5 5 5 5 51-55 71-75 56-60 76-80 1112 15 16 No. of animals Male Female 55 55 Satellite study (4 weeks) Animal numbers Male Female 81-85 91-95 86-90 96-100 Cage numbers Male Female 17 19 18 20 TEST SUBSTANCE AND FORMULATION Test substance Idnaftoarsmhaeteito,nwshuicphpliisedretbayintehdeinSpthoenssoturdryegreacrdoirndgs. the test substance is contained in the test substance The following information is given in summary: Identification: POSF, T7661.4 Description: Liquid Storage conditions: Room temperature Supplier: Sponsor Batch number: 040227 Date of receipt: 14 June 2001 Quantity received: 4 x 20 kg Stability: Assumed stable for duration of the study Purity: > 99.5 % Atemspmearlaltusraem. ple (1 ml) was sealed in a suitable container and stored in Archives at an appropriate tThheemSepthoonsdosrowf asysnrtehsepsoisn,sfibablericfoartiothneocrhdaerraicvtaetriiosnataionnd ostfatbhielittye.st substance and the documentation of 12 : MIN 313/023622 ANIMAL MANAGEMENT Animal supply, acclimatisation and allocation ALoftdt1o,1tMaglaforogfra5et5ea,cmKhaeslenext,a.nEdng5l5anfedm. aTleheCrral:tCs Dwere(SoDrd)IeGreSdBatR4r0a-t4s4wdearyesreocfeaivgeedanfrdomwiCthhinarlaeswReiigvhetr r(aUnKge) bOsseeenpqinauagreranrtirceveelapyle.o,aftthecedagauennsimtiilnalesthawcehebracetatrgeeermy,hoevolenddetfahrneoimmapatphl reaottprraainatstimeitenbuowmxaebsseparlnaodcfeadallnoiincmaaetelasdc.htocEasatgucehdywsiectaxhgetwhsae.spUarsolliconecgdauttherdee tbTihmrheemeeadeldaidndtiegiasttiteoclHnoyaleoulanplctyooh.nnSsreicTgcrneheemiepnseteRnftoedrpooorcferuvatmnipeieuwmnbtalasilnsshwdienesdrcuelbbuysdseeetqhdnueteanatotnhiaemrHaclauhtlhnivstsiiunncpgrgpe.dleionenrrweLlaaifsteinpgrSoctvoiiedntehcdeestcoVuHrerLetenSrti.nsatIarnytuasdSdeoirftviotihcnee, bTeaqtahtuwetieelrcieibaekrgslaeytsesidonc,toeatnrhsvsataftialtsurpttaioonssgfswuiberatlashecephreramngcvritoniiruciomapnbimlwseee.enrpAetoadslbdsliioibtniclofeklneusadeplnlaytcto,ieagsbleavthtaatreeririrsaiiebtnisyognossffe.rxcoamagnedsthwtehiereregsprrooauttaipatsledwdaiesrrtoeruibndudistiptohenersrewodoermine Encauagmcehbelaarnb,ieamlsawwl aewsllacsaosaltoshsueirg-incdeoeddnetiadtynauocmfctobhreedrionacgncdutopuangnirtqso.uueplyaniddewntaifsieudnwiqiutehliyn nthuemsbtuerdeydbwyitahtacialgteatatonod. sEtuadcyh tT5fro5ehraetftoemam5ne8animltedcasa.olysms wamneedrnetcheaedli.lrobFwooedrdythwtooesiegahcactnsliimwmaealrtseisseienltetohcetethrdaenfogcreotnhodifsit2is3otu9ndsgy,dtotehs2ec9irri2baeggdefoabrtemtlhoaewlesstfaoarrtnod1f41tr7ed0aatgymstoenb2te0fwo9aregs The spare animals were removed from the study room after treatment commenced. Animal housing, diet and water supply Awmdinaisnsiinmimdfaeeilcsssteiegwdtnheewerdeittrhahanonadusbsfoeeaprdceetneirnarcisteceididodeeft.oasurmcehsitnraiigmceteinsdtesetbnhetertwyeernoetrndyernootoffmeaxsc.itleirBtnyea(flBobrueiioltldhoiegnigsctaYuld1ya4n,tdhRecorhooemomm0ic0wa7la).sagcTelnhetaesnfeaadncdialinttyod Efialtcehredanfirmesahl aroiro, mwhwicahswkaesptpaastsepdostiotivatemporsepshseurree awndithnortesrep-eccitrctuolattheed.ouTthsiedteembypeirtastuorwe nansdurpepllaytivoef hPhrhsatuuoeunmmrudgiroyiiesdddscoiiittcrouyyentccctwcooihnomreeudncreoetekr.dusomslAwwsdoreeawntrrireifeketiorc1pmeri7eeaadrlmtdo2leaic4gi2onho1hnttnoatiinuinCntgrhueseo.dwaunnaswdsulyim2ct.h9obinentRtorratooh7nle4lfge%edarsia.rtnoogcDchgeceiaavvnosiegaifoetains1oc9anyilnlsctyolwtehde2eoer3vfeaiC1nam2tiemiahndnaooldurfrrrao4sonm0ocdmotthonsaa.tridg7ne0uTnt%ooeuam,isnmprdleeipsgrtapahhcetteutcartoaeinvncdetatulnh1yade2.l 13 : MIN 313/023622 Aeshxlocaeurmelddsetdhw.eepAreubasltciactnivsdau-tbpeypdlyeiflfeatchilte.rriceitwy assuapnpylyfawilausreaovfaitlhaeblveentotilbaetioanutsoymstaetmic,alolry tebmropuegrhattuirnetolimopitesrawtieorne wTicsahoegerleae-taitnorsainumy.sspaT,lehsfnoedwoecdedarhgeoeahspbopowueversesreedaamnbfdisavodwereaboteoefnfrotabnopesttatasplieeenxsrlewpsweserrhseitccecaheghleab,wnoguadensydlewcashtsiaatthnphgpiaserodsntpauraiimnatltbeeaespirsnpwstretoaerpvserlarilmaestd.eeuschiendltiedbrvyaanlmds.oflrotaoClri,atygaenosdr, DnToorhieewatdhafdrenoenimdmuaarSlnisntpieewbciweoirataeilscDabolilereoitonwstgheSedcerorfvclrlhieeceecemtsaeocdLcttheadesn.sr,daWtpooeviutaehtriascnmtiaogn,rhdEptasrbrsodeepfxrho,oyrdeElaenrcnogttiulcadtniianedget)e,(nbRetl.oxaoct edapnstdadmMupriolniungsget.hNTe ho6i.sh1odMiuertsaicneoxtneptnoaaisnnucerede tWubaetes,r etaxkceenptfdroumrintghtehepu6bhliocusruepxpployswuraesofrrewehlyenauvraiinlaebwleasvibaeipnoglyccoalrlbecotneadt.e bottles fitted with sipper Ebkttcahhhpynaeaepoctmrrwhsmeouingvbcpiuegaapaldhltlsacittebahtihhrneo.aefdnovosfDerSmedieppniipucarecearnbteojrylutwibtmsdhbihaoieaecseltnoedcrtadeghnsoibtcuaohyfallfetytlhstdssheceitoeoeudEftndnDtrywtahov,emaeuitprsshtoiaienernnreaytevmmnllaeayteraesrnie.snobtet)nuyd.SosftotufhCaorppnererpaEerulltssinysiueefevsripn.cei'ptrssaeoltTdinaede.hnsmiredaoeflqyonnfutrotai,atcnvlaaFpialtlroryyoicosovoediusirfdstiwtaefhnnieecdueravetwtriReidratseuietoecrnwanrecliaeesvlruAeeopcdffposfrlacmcoyirourupnsittositiannn(gmfeeiosonleiyvrtndmseafrrtenaaioronnelmdnydd Nanoalyostheder, asspneocinfeicthcaotnmtaamyihnaavnetsinthteartfewreedrewiltihkeolryptroejuhdaivceedbteheenopurtceosemnet oinf ththeestduideyt woraswkantoewr nw. ere Administration T13hewveaepkos,uCr-ognentreorlartaetds frreocmeivtheed taeisrtosnulbysctaonncseecwuatisveaddmayins.istered for 6 hours a day, for 5 days a week for Tssddtuiihrrfbeeefsaecttmrtaeelnsyntoctemfilniaaqwtiotureaifrsdtoiharfmeleaweededtamexsrrpiaendotdeiesssultitrrovceaeotrtinhoecthdenroattmlvoolaebatpdhenorebr.ayirlsaltethgTrselhabfeisrynosfmitvunaasrhipgaaooenlnatutpriicinoushfnmeuarmsfpriaoobanmnendrdpgsuucensonmoineunprctg.aeotnsenytdTlrryahianteseigoxaenvpsvaoapwospoufaouraseurn/rcaaahaicprtahpmmimreoobvispxeeprrdtihsua.ertbereeyTv,phaiauenlssuttsioeene.sgdat The target concentrations for treated rats were 30, 100 and 300 ppm. Control rats received air only. DTheeverlaotpsmweenrteseLxtpdo, sHeidtcthointh, eHceortnfotrrodls/theisrte,aEtmnogslapnhde)r.e using ADG snout-only exposure chambers (ADG Arpderolsolstgiranarngeinis)m,siniavfgolesrlpy(r5io(n0ccc.elo5dun,uds1rien,ec.g2u,tri4eTvseahenerddvrae6ayst)shsowpwurerierosreerfostruroebDsjtteharcaeytisensd-et5adtrtotooron-e1cfsetrerexapspiepnoretscupdtirarveoysec,,leyidin)nu.crroeesradsaeinnrdgtoethxaepcoc`suSeshdtoatmmo adainorismoinnaglly's (ptSoehriatohmde DpreetsaeinlsteodfinadAmDinMisItNraItSioTnRaAndTIaOnaNlyOsiFs PoOf tShFe BteYst IaNtmHoAsLphAeTreIsOtNogTetOheRr AwTithS athpepernedsueldtstootbhtiasinreepdoratr.e 14 : MIN 313/023622 SERIAL OBSERVATIONS Dpsatnruaoitdmceyedadlwusarnimetdhaiwsdnieegtrnhteheerdroaeurncegiocmhrodoareulddtsutnhionieft tadahlasleywawScetteilulvrdeiaytirseeDstcooaryretdhlaeBetdion.gogrko.tuoptIhonebasdedardvyiatibtoiyonn,dsaoybansredurnvenaxitaniomgnisannardteilomantaisningotuettnolianniencddeiivonifdtuthhaiesl oSbesriearlvaotbiosnesrv, abtoiodnyswpeiegrhfotsrmanedd foonodthceonasnuimmpatlisonf.rom the Satellite groups were confined to clinical Ainldlicoabtseedr.vations described below were performed in cage number sequence except where otherwise Clinical observations ACldoaanotgiesmeeasanflaadsnetcwdiemescr.eaegoAeinf-ntsorypaneysdcesette,vwdideauvrtieriosaunitniaosflnrplyoeamcanttdendlpeoarrdomsatgialtrylweswifscoaerosfedrtvaehiicedlyoeornfdboceserdeerovavfteididtlhel-cnehocetneiamdloitethfioiialnnlm-,hroaeesnsapgaltesphtcpttorhoroeprfreoniaacactctetuui.orpenanatton(sdt)r,eseasvtumecrheintayts., In addition, detailed observations were recorded daily, on the days of exposure as follows: PDAArssuer-eliaeantxcgephoaeasxsnuppiroomessuasolirbbewslee[ahrsvionarwettihteouvenrenwre,odorkbtoisneigrtsvdahatoiyomnewcaasgeseverely restricted due to the tube restraint] Ignenaedrdailtihoena,ltah.more detailed weekly physical examination was performed on each animal to monitor Dreucorirndgedthaet laecacsltimonactiesapteirondaayn. d recovery periods, observations of the animals and their cages were Bodyweight tbThehafetorwtereenaiegtcmhrtoepnostfyec.aocmhmraent cweads (rWeceoerkde0d),onweeewkeleykthbreofourgehotruetattmheenttrecaotmmemnetnacnedd (rWeceoevker-y1)p,eorniodthse, danayd Food consumption rTfceoahcrlecoutvwhleaeertyiegwdhpetfeeorokirofedfbaosec.ofhdorcFsearugoptemrp.elaitethmdeestoentereascctahorrtcdeasdgeth(,Wethemaetekraen-m1wa),ieneainkngldyaecnaodcnhasnuwmeesptetikimonathteproeourfgaahnnoyiumtsapltihl(leegd/trraweta/awtsmereeeknc)ot rwdaneadds 15 : MIN 313/023622 Haematology, peripheral blood DoanbuatraeiinsntgehdeWsifaeroeinkmdu1ac3leldoabfnytirmiesaaotlfmslueranaftntee(rbaenofdvoerberlnoidogodhstsinasgmt)aprlavenastdiwoinen.reWwAeitenhkidmr5aawlsonfwfrreeorcmeovthehereyldr,etburlono-dooedrrbistlaaimgl hsptilneugsse.nweerrael Bfolloloowd isnagmcphlaersac(nteormistiincasl:ly 0.5 ml) were collected into EDTA as anticoagulant and examined for the The folloHHRRMMMDPTwloeeaaiaeeeftdteietfaaaianemmcennnlbglurelwaoeNLEBMLccclowttogneeehoyoaoaecctleolllricmssdoiullloyrtngaioreebthhvuntilpoecrpetiaaonooemchcWnhsueel(tppleyouiHlmmne((l(hhltBcmlHRPassceciiyootCsoslclltebe(atssggtu)ouBte))i(llircu(n((nsMooc)eMNEonet)bbd(u))dt)L(iiCnRnnu()cWVtsBe(ciM)nloCBlgsn)CCc(aH)eLBnU)tarCya)teiro-nTe(MchCniHcCon) H1E haematology analyser: Ranedticaublnoocrymtealcitoiuesntu(sRinegtica)S-ybsrmilelixanRt3c0r0e0syRl ebtliuceulsotcayinte, eCxoaumnitneer.d by light microscopy for reticulocytes Bumnlioucorsoud/amlfiaclcmerlol c-tyyRtpoeossmi,s,ainhncyolpwuods/kihnyygpsnetroacirhnm,roomebxlaaassmitsai.nweTedhreebrymecoloisgrtdhcetodmmamsicforoonlslocmowopsry:phfoolrogaibcnaol rcmhaalngmeso,rpahnoisloocgyytoasnisd, ++- + === mnsloiogdahbetrnaotremalities detected Aredspdeitciot noaf:l blood samples (nominally 0.5 ml) were taken into citrate anticoagulant and examined in Prothrombin time (PT) using an ACL 3000 Plus analyser and IL PT-Fibrinogen reagent AILcAtivPaTteTdrepaagretinatl thromboplastin time (APTT) using an ACL 3000 Plus Analyser and 16 : MIN 313/023622 Blood chemistry Ap(angltaoisttmamhteieand.aslaAflmyofret0ea.tr7timsmleeepla)asartwnadtfeiiorvuenes,icnmtohglielnetuphctleteaessdsmaaimnantedwo aatlhnisteihemixsuaaamlmms phianleseepdfasoriurinnbprseaeessrqipupaeehncntetitrcloayofl:ahcgeaunelamtrniatf.tuogAleoldlgytiu,nbfeuosrrtdwheeerrretbolmosoeecdphasaraanmtiecpatllhelyes Using a Hitachi 917 Clinical Chemistry Analyser: AAALUPICTCGTTCCTSSnoaooooorrarhsllrloiakeuetcerdpltttlgracaaabnaaotaaciaglasllliuttiiloryruasiitnitimBptcosnnnecidnmaeeuhrlieeeieitondlmoce(rad(iP(ptNeie(lrGmeCdepCeahhuh(aih(esmhlayioobKnlC)utsny))odssieic)rodn(pps(nrre)TTrtopohhoar(oolghraoaBttgi)rteont(kgaaieaCnrsli)lnnsiunfah)esPaessaofsrrese(a(leoeA)rPs(ta()LehL(sSCoDeP(DsAP)H)(HKAL)TTSTo)Tot)atal)l)and iso enzymes Electrophoretic protein fractions; albumin (Alb), a1 globulin (a1), a2 globulin (a2), p globulin (Beta), YPognlcoebauul-iSn a(nGdasmcamnan)inwg ewreithaanasluyistaebdlewdiethnsiatogmareotseer. gel, using a Beckman test kit, staining with Aallbbuummiinn/cgolnocbeunltirnatrioatni.o (A/G Ratio) was calculated from total protein concentration and analysed 17 MIN 313/023622 Urinalysis Dai0nl7uld:r3iaivn0nii/gdm0u7Waa:l4lse5.emkhAseontua1ir3bmsooarlelifssstmprweeeacrttcmeiavgedeenleypt rwtahinvietdehdfoWouolletfoewwkfoain5toegdordffaorryoer.mcowvaaeptrpeyrr,;ooxvuimerirannteieglyhwt1au6sr:i3nc0eo/1lsla6em:c0tp0eldehsouuwnrestirleancadopplplleraoccxteeiddmiafnrtoeamlyn The individual samples were examined for the following characteristics: AVoplpuemarean(Vceol()App.) pPSSHrpooedtcieuiifmnic((PgUrroa-Nvt)iaty), (SG) potassium (U-K) and chloride (U-Cl) MpGaascolucsuqoilctturioiavdssltieeiintxago(tGaritvrolneeutechdgi)neia,adtfgikiovnceleaoltotosootwnirnecsilsnyroge(fwaKcagohenentianolvslt)yets,ntreboteiiboscltuenoal:nitpnscieegfdnmotrfreraongtimtlosuncB(.oBsaiReyl,iee)r,ksuephltlatocsen,mfeNosrepawhingabdmeumrbeynil,ptesiEgpn(miBggellmaonnotesddn)taasrnbeadyrreewMperouerrelptteoiusdrtstieexadds. +0TR === nt`rseamgcaeatlilvaemount' of analyte Awsaammspeilcxeraowmscaionspecdiecnfoetrrxifathumegiepndraetaisonendnctoehfeotfhretehsueulrftiionnleglowsdeeidnpigom:seitnstpwreaasdpoenrfoarmmiecdr.oscAonpealsilqidueo.t oTfhtehedeuproinsiet ELECCOSeprpratyyhuiestttsecrhhsmtroearcoallasiybctaotnylezotsceoresmallasanl dcopmrepcounrseonrtss (Cryst) ((((((ELRCSAppeBabeuisnC)trc.sm)))) ) The grading of cell frequency in the centrifuged deposit is as follows: 201 === FFNeeowwneiinnfosauollnmfdieeinlfdieaslndeysxafeimxealidnmeeidnxaedmined The sample residues were despatched to Exygen Research for test substance/metabolite analyses. 18 : MIN 313/023622 Urine SEM x-ray analysis IwngTsiSdnaerEhhedomceMeniurvprotpesiilpfadesiasptmsucyunoaaw.bpistlmlsiseeuoTiarsdbrnehliles.nweesce.dpoeuuarlsrFleratiecinmonchiertngpeeaslddteaanhsdtmifeomdrwopilPatmaelilelsrosysetntmhfwwcaetooioeelulaeirlnnttkeehhgicmoiotUmetsfoadenmrlseipfcvecrrwooedoolrmiidvlstaeuehitcmtreciytynleeaydf2iaaonanorhssdsvopsctaeuufearyrdcrloncseiymmiudgfaloehinfslntoaliaomrntfdewodpaulrlHliricsniturnegdyrugiussalnitrintgaanihinlhlgmiygstassaaniWilsonasmntleaeydienricsuvnkdirrsaoit1lnmheb,3gleyeueotcWraaSiftnnbrEeeioeomxMedlpkwiaetole,X4ashsau-aoonrrscaelfdsdoy,aeilpryxnleeerspglcec.eooptrmesovauTdroeerehrmneadye.tt NECROPSY AND HISTOLOGY Method of kill Arreeexnccsiooamvvneegarrluyysinpkpaeitelrilroieoinodd.dwduwTarsheinresegesleekthcqilteuleeeddsnttcuoebdyayilnloianwwntdrhasiaptchtehiorsifsttaehocentseouaarrnylviimiivnniatjneelsrgc-tgwiuornoenrtuieplokftchiolesmloedpdeinauradmifstooenrpf.etcnhotemobspaclrehbteiidotounnleeod,f tftrroeelaalottmmweeenndtt booyrr Test substance/metabolite analyses hSealmdpulnedseorftebrlmooinda(lfsoordsieurmump)enwtoebrearobbittoanineeadnaaetsnthecersoiap.sy by cardiac/aorta puncture while the rats were Tsehpearbaltoeoddasnadmfprolezsen(uipn tloiqu4imd nl)itwroegreenrupnrioinrttoo tduebsepsa,taclhlotowEedxytogecnloRteasteraorochm. temperature and the serum RSaetseildliutaelrastasmdpulreisngoWf uereinkes 4fowlleorweifnrgozuerninaanldysdisesppaartcahmeedtetorsEaxsysagyenaRndeseuarirnceh. samples collected from DniutrroinggennaencdrodpessypasatcmhpedletsooEfxlyivgeernwReerseeacroclhl.ected from all animals. The samples were frozen liquid Macroscopic pathology All animals were subject to a detailed necropsy. Aptteohxeferptafeonolrlseroemcawdkeradoaen.bnvddsiAeeeawrxlvslasaemootxicfoitinenathertnedoeadfilhntthfiissseetisatoubutrue.ryrasAeinaosnn,fyadpneaidtatbhucnoehitoratirhfarmiyoncriaemaglsclpaaiwlcon,,esdriaateaibonfdenudxo,lamlcmmrmianoinnaaripecladrhaloonvnsldcieosorgpuvpyeaeillcsolv.yri.ceiAxncTatfaemthvereairitncicvaetrietsaoinnonatinrnawadlloartmsfohroetiehdifcre-wolvirntaidisessecsrdeiuen.remacsiowswivoeearndes, rTeexhcaeomrrdieneqedudiasnaidtsetahoperpgrreaonqpsuriiarweteed.retAiswsnuyeeigashbaenmdoprlmaensadlpitreyexstieenrrvntehadle iananpadppepcarurotapnsrcuieartfeaocrfeixssiaztoeivfeot.hfeanoyrgoarngsananadndtistsisuseuse wweares Any photographs of unusual findings were taken at the discretion of the necropsy supervisor. 19 : MIN 313/023622 The retained tissues were checked before disposal of the carcass. Organ weights rTehceovfeorlylo, wwienrge doirsgsaencste, dtafkreeenoffroadmjaceeancht faatnaimndalotkhiellrecdonaftitgeruo1u3s twiseseukesanodf tthreeawtmeeignhttsorrec4orwdeeedk:s of ABHKLLuirdievdanareinegrnrtnesyawlssith mainstem bronchi (Lungs & br) Bilateral organs were weighed together. Fixation BpTinreodesusuteiesnrstvr'iseaadnlsdoimnluee1tptih0iod%ynildanytSeemduaimtdrsaepplslierbiwsut.fe(froeeErreytfdhiexesfeodwwrmehinraoellieBnf).oixuoeifdnt'hsinesoDoltuahtveiiordnts,iospnsur'sieosrfllutioisdte.trdanUbserfilenorawroyffrbtohlmaedsedaelltrisawsnuaiemssaftliosxew7d0e%rien NAABDEEFHHHKLLLLLMIJOOCCleeaipauyyeraoaduaeioepejvamadrcuiuenmesraalsorrtemydiohdnimesactongdrdnrucnaipntnrlueepu*smderxyhrynamt*hm-nyi*um*aalseaatnumsrrnhrgnaomiy*vdoniuladdegraajsgesaeoltraslecseiannsiancdtd+-s---sctmmaruaeadcnshaedleniobte-ubrliracornchial PPPRUUVOTTTTTSSSSSSSSSiarckapttekprhoehertavteooaneimliiseiuclynygaarinncnmsertcltivmgnrriettuehieuaatrnoiianauuasatneecreslmuaitarcaemrysaadecysylanhl*sobnemwvgrldredalivuastdceshnideccsdper+llsveera+*sir-xatthhiygrhosi+ds +a SOenctliyonosneinpcrloucdeesdsethdefoprelevxicamepinitahtieolinum : 20 : MIN 313/023622 waSnahdmerspeelceatsiloeonsfeioadnnayws aaabspnpnoroortmpcrailaeltaetri.lsysudeeslinweearteeda,lscoonrteitgauinoeuds taisnsdueprwocaessfsiexdedfowritehxathmeingartoisosnly. aIfnfetchtoesderecgaisoens Tfuhritsheerxetxenamsivineatliiostn ooff ttiissssuueess. preserved is intended to satisfy any possible future requirement for faSeramemrueprtl,aesisnaeolidfvatahrgyeaighnlesaatndadn,(yisncfciualtutuidcriennrgeerqnvuaesiraaelnmdceasnvktietfyloe,rtpamlarimcarnuoasscscaleolps(itichniuegxshea)smwainneardetinonanos.topexhaamryinnxe)d ahnisdtothloegirceamllayi,nibnugt Histology Fsuobrjethcot stoe hainsitmolaolgsicsaplepcrioficeedssiinngth. e Pathology section, the relevant tissues with an asterisk (*) were mTa isisctsaruonednastrahdmicppkelnreeisosdswiacenraedcidsdtea/hSinycedhdriafwtfe(idPt,hAehSma)ebmmedeatdthoeoxddy.ilninpaanradffeionsiwn,axex, cseepcttitohneetdesattesapwphroicxhimwaetreelystfaoinuerdtousfiinvge Those tissues subjected to histological processing included the following regions: HLLUTliguirrevaihnanectgrarhtmsre--y-aisicsnbe-reccloiactlnsiudtcociddoolnueenpdrdfyrfe-oradaoumsnmerbdiciacfttcluiuwloelrmaolnclrsaamptaitirnnaoaodkjnlloieovfrnbeelernosasatbtrgieiocistnu,altlioalnyrdirne(euxcgsl)uiiondngesobnroenhcahlif for SEM analysis and the other half for Foof rthbeilraetmeraailnoinrggatnisss,useesctrieoqnusiroefdbfootrhmoircgraonsscowpeirceppartehpoaloregdy.. A single section was prepared from each 21 : MIN 313/023622 PATHOLOGY Light microscopy Microscopic examination was performed as follows: Aaannlidlmt4iaslss(u3ke0isl0lpepdreposmerr)dvyesidancgfroidfriucereixdnagmotnhineactsoitomundpylw.eteiroeneoxfamthienesdchfoedr ualleldantriemaatmlseonft Gperoriuopds, 1an(dCofnotrroall)l TalilsMsuaeisnrsetpuodryteadndatRmecaocvroesrcyoapnicimeaxlsa.mination as being grossly abnormal were examined for Tdohseagfoe,llwoweriengextaismsuinese,dwfohricahll Mwearien cstoundsyidaenreddRteocoevxehriybiatnaimreaalsc;tiloanrytnox,trleivaetmr aenndt alutntghse. high Fpfoainltlhdooiwnlogingsgiswtfeuirvneedeeigrtthroaeodrkerseappwoeraetserdruesaveside"wp-roemsfetihnntei"mmoairlc,raossssliciggonhpeti,dc mfainosddeivenregarsti.tey, gmraadrek.edInotrheselvaettreer. casAe orenveieowf itnhge PCNA Staining for cell proliferation wpd(S1reeea,gc0rcrte0tieio0eccnaocsbouelnofleltfs.ec/udesrle,ilcnatpaniorrdyonle)bixflieaanrmdadotiienrodrenedwrbpetryroeetsthdeaenekttpee.narmthfArionolemtoogttahiaslellt atoconefilaml3s,sap0elr0sso0slfiotfhcreeerPlalCstseiNocwntAieoirninemsdemacxnou.dunncoPtoseotudasniitntfirviSone-mgpPhinCa3soNesreAdppeoarssrittataoitivenaeisnsscegeecsltsclisoet,hlnliessf Icnonatdrodlistifoonr,thseecitmiomnsunoofsttahienindguomdeetnhuomdolforogmy. each animal were taken and stained to act as positive DATA TREATMENT ttTchoohegniesstuahrcmeecprploiwtmirotiatncht.iossnaitgtainoinsnsdpasetearriiacolodlolebicnstecerlduvdadteuidorninsingptethhretiasninercienrpogoptrsotyarpellelrawitoeede.ktosTohthfeetorenWalytemeskeen-r1italabnoodbdsryeewrcvoeavitgieohrnytsscroaemnladptilnefgtoeodtod, tptcSohouuemrrmpecppomoursmaoeterdspyr,u-uhscstteoteoarwtrthietesoedvtiepcairnsr,ecd(steiehevr.entgiadyt.ieunmwdalneemaurreeanmawsubnsasedunraaadtnloalsdyf.tadsrntToeadcuhnainedmrddasaeruldddmepdtvomleaivacaftieeriaywsot,ineossdrtn)aipsftpiflseaertexcriesecaensscn.ttlatyfeInotddurisistein,hnaettgchhheitinhsrpederafierpovparrimodee,srueteantnwleotrtede.rdageteFainncowedarrliecavprulirledlyeausstpaeetolondrstdaesfardtitiboaomli.nen Throughout the report the following abbreviations are used: NRSDoronr sd NRSteuacmnodbvaeerrrdyodfeavniaimtioanls. examined. : 22 : MIN 313/023622 Definition of "Week" Tosanhmethefeidrsusteravwteieonentkh. odafytrefoaltlmowenint gs.tarSteudbsaetqmueidnntiegxhpteprrimioerntotaltrweaetemkesnotfctormeamtmeennctinagndanrdeceonvdeerdy awtemreidonfigthhet Signs Awhdicethaitlheedshigisntowryasoofbinsedrivveiddu. aOl annlyimaanlismthalastwshitohwfeinddsiinggnssairsepprreesseenntteedd.in Appendix 1, as the weeks in wOebeskersvoaftiroencsovdeurryinagstfhoellroewcso:very phase are recorded on a study week basis. Weeks of study relate to Week o24351fRRRRRrecovery Week o1111154678f Study Death code key HF78 ====rtfheeorucummonvidanenardeyleakkkdiiillllll Appendix 2 presents the individual observations of signs related to dose administration. Bodyweight Group mean weight changes were calculated from the weight changes of individual animals. Food consumption Vanayluaensimpraelstehnatteddifeodrothr ewaams koiullnetdodfufroiondg tchoenswuemeke.d in each cage in each experimental week allow for vWaleueeksl,ywghroicuhpwmeereanwfeoigohdtecdontosuamllopwtiofnosr aanndy dsteaantdhsarads dfoevllioawtiso:ns were derived from unrounded cage E[ad. fc] Xw = Z(ad) E[ad.(fc - xw )2] E(ad) -1 Where: x w = weighted mean, ad = animal days, fc = cage value and sd = standard deviation. Blood chemistry Albumin to globulin (A/G) ratios were calculated as: A/G =-T--o-t-a-l-p--Ar-o-lt-be-ui-nm----in-a-l-cb-ou-nm--c-ien-n-t-cr-oa-nt-i-co-en-n-t-r-a-t-i-o-n: 23 : MIN 313/023622 Urinalysis The abbreviations used in Appendix 7 have the following meanings: MPCCYPMYYY PMCCalleooleduuiddyuyyem,,llpmoyaweelledlaoiyupwepmlelaaoyprwepalnelaoacprewapneacaperpaenacreance TR Trace detected. Gelreocutrpolmyteeasnosnlayn.d standard deviations are presented for volume, pH, specific gravity, protein, and Organ weights ttwttTcoehhohreeevmeiegavoairhaarcniirtdhaagsinjaliugncbb(sreaaiotol.leni,dudtdypuyTw,notahthraefrigtessaiegasrnraeunhsnfamtfo,waollriltroneyehmwigsugietsishhtdnhret,tgseeotmteogplhrikrorenmoevetusciihsepnnoenagvftlomtaetrrrbhadeioeanaadtilsnenlefy,fogwfoTrreramreoacgtibuthgealpeodhnesrftsat6bwwhbaoaeseasdonirngytelhdtuhwhepttAeeesac)irpugooapshvwrlugletae.eaanrlrilndeaTtuitowxhena.eaeod8dinsjLgujtewuahisnnstteaseetdrneadeaoadrrsttdtrhshoettehodawgrense.raeevdrrsiadTeasfrssrihtdoopieomnotdhnnieelsnvsitdnhewiaoieevevtsviiraoeadwerrnnuiaebsaaalr.alblleyslseoemfiirdstgaetnaoeaonnddnf Pathology tnpTdoiortesihesssrsesmuceurreanietblitss.saecswtdhuiToheenidiasscs.sushuloeec`dfNsoduofraoeldtcrasonietrgoxhdntaeeimbdftieicisanaessanuxttaeaiobsmlnnesionsptriheemodecnraie'aflifreemoidnrsaepicnterihnoctedsihfcieicoemapdptiirecciosrnatoolttslhhcycaoeotblpautifphctoperfeopnhtuiadissntishtxduoo.epltooaTwgthhbyaoeesloanaebgpoxsipracememannlacidlneeiexmxod.afimcaarinonIcdsnaoctmfoiooapmulnilcnepadntlratletybfocouearldbareeear : 24 : MIN 313/023622 Statistical analysis All statistical analyses were carried out separately for males and females. Danaatlaysreeslawtienrge tcoarrfioeoddouctounssuinmgptthieoninwdiavsidaunaal laynsiemdalonasathecabgaesibcaesxisp.eriFmoerntaalll uontiht.er parameters, the The following data types were analysed at each timepoint separately:- . BFBPOaoolrotogdhodayodnwlcocwoeghnieigescihmugatmhl,istfupstir,nstyiibdon,iongnht,gahgoesaa,vmibenfasorstoroaoltpulvhopteeegrroynaapunaprmdnipadrbatoedeuprjrsuritoinsuaftadteleaydynsspiftimouesrrdaityolesdrpwmse,riiuitnohsadilansnbgdocdwuymiwthueoliaguthtivteeacchagfientdoitnagl.s FFoisrhecra'tsegEoxraiccatltedsatt(aF, isinhcelrud1i9n7g3)pfaothr oelaocghictraelatfeinddginrogus,ptvheerspursopthoertcioonntroofl.animals was analysed using Fvwneaoecrrrieeascnstohcaneerytnib.necutoowmuespeandreathdtaew, giBrthoaurtphtlsee.tCt'Uosnstitenrosgtl tg(eBrsotasurptdl,eeitpntecno1dr9pe3no7tr)aotwinnagtsheafdiojruussttctmoapmepneltieofdofrBtmoaruttlleteisptttl'esthcteeosmth,optmareroiasgtoeendnsegwirtoyhueproesf Tanhde cfloinlliocwalinpgatsheoqlouegnycdeaotaf statistical tests was used for bodyweight, food consumption, organ weight Ipvagfnraroola7upul5yepo%ssriat>sigoocawnf,isntaahsss(etMaatpdhpapaepnltlitaciceeoal(dnab.1tclre9ro.o6Tls3rbs)eoaaattlhnmldfgeoanrroltsuio)gprvspoa)auliwuprwesesriwes<eectrhFeveiescrshsoaeummrs'sepvaEavrlxaeuldauecseut,>stief=noscgtr,seaa(xnFMadimsafhponerltreeili1c)9,tve7tas3htl)eunfefoosrar<afe=raectcrqhevuneeddrnoscusiynes Itr((heWHf seBepnialaollrinpetaslyameertastw1m's91a9ets9et97rns)i1tco,wftoa1marn9soav7nln2ayor)osittaiwosnnsaceiwsge, naaDhsipofupimcnaliapneonpedgtlt.eite'nasdItet.fietttshyhteIe((fBDF1ta1%uhrnettlneelFeestttv1tte1w1lt9,a9e3ss5W7t5)s,iifwlgo1lnira9ais6mfmi4ncs)ooa' wnnttoteas,tsisogstpnunfiegicofrgiifrcteoyasrantmiotnmefgadotdtntihonhoassetteote-n1tarh%iedces.pldteorovensneselde-, Itwts(rhSfiageetnrenBesHeiffal1oiarc1rtpaltm9eepn5tslatti9tt'easi)wdotw.ntathsaesessIwstpf1iege%twrnrhefiaeolfesitrcrvmHiaeesn1eldi,tdg.,StnieshniIusfisftigrtclegBeafaeoynadsr'trs.ttilmnteaegttostt'ntshtfohoatteeortsntathi1cmew%itoadysnoolsosetetfvoi-lenrldeli,oscspsitgeotrh-nenreinsefnedsicpw(aolSnonahtgss,iearntlrheio(teythHnmme1na9ioclo7nen7yo)-atponw1and9raea9s,m9saS)qeptutpewraeliricalee'ssd-tre.tnoesootsIstttf twWscheoheqhviueac1errh0eina%mctaeeip.lgwephvrFhtoeoeilpnnrr(fiAotlahurtnegeeg,nawencareivntwhtaaheillnlyeigsagohinsrrtodgdouaCapnftaarcwre,olelsvaaitagnrtiorhaoimltanysn,s.schi1seip9o6wbf3ae)vs,tawiruniesaeeanndnceoairntwgteaapmnslapwpcteeetriofgoohfartmlalaonenwaddlyufbsosoirisdndygoiwfftfeeevrirgamerhniitancnweacslaebsinoisndibgyotnwdhiyefeiwicgaaehbniotgtvahaestt : 25 : MIN 313/023622 (SSpih<gin0rli.e0fyi1c')asntoetrsdt0i.if1sf%edroe(nnpca<ete0sd.0bb0eyt1w)`+elee'vnaenCld.ontWttreiolslltisaamanrdse ttdreeesnattoeitsdeddgebrnoyout`pe+sd'wbyer`e*'e;xDpruensnseedtt'astttehset i5s%do(npa<t0ed.05b)y, `1*%', QUALITY ASSURANCE AND ARCHIVING PROCEDURES Quality Assurance DSteattaeimlsenotf. the Quality Assurance inspections and audits are presented on the Quality Assurance Archives FurSSesocttaeileelndnondtwcidaoeruisndnr.giOnaTgncpyodeapmrnaaepytrsiclneohSgtifipvoPsoinarnnomgsocopefmrld'etsuhaariysoensrdbs.tessuupddpeyipcsilpamileolres'rensadwwaonhdaficlayahtasft,iaesr,srepwtuehcneeisrmeupieetsnartbisoolredae,nsddbsiyntsaartetmehadepsolieannsr,coHhefiuxvinncetessitpnatogbtdfihloiHotnysu,enLftgioifnerengleodSrnocagniteetndLecriemfoesr ASclliednacteas.generated by Exygen Research and Plymouth University will be archived by Huntingdon Life AAtcdhoilesnlcctodoaapartchdtyteeeeroddofawfaptnihipstdershouofapeiudnrtvioaatilfhtcetereheseSpspoopefuroictngnimahaslnoterdrnoe'ssnpaoklatlrnnhtQdoe. wuraAealbecltiodotvtygrhedeeAs.resewsnquidulrliarobnefemcterheeenitnatfssii.npveeedcUytifneoodanrerarrreemnctoeoinnrcditmiisorcunwumpimlelpsrbteiaoernidocredethtsaoeiwfnSfeilpidlvoeainnnysdyoeerafiriwtsneiimfltrleolbbymee. : 26 : RESULTS MIN 313/023622 CHAMBER ATMOSPHERE CONDITIONS Chamber analysed concentration of POSF tTohtehidsarteapaorret.presented in ADMINISTRATION OF POSF TO RATS BY INHALATION appended The mean chamber concentrations (ppm) are summarized below: Mean chamber concentration (ppm) 226 G1r30o4up 2949 The achieved concentrations were close to target. Signs and mortality (Appendix 1 and 2) AtbhonedimysttaueldmyN.poe.rTa6ht3ui,sreGa,rnpoioumoparl1rihg(aRhdeticnsoiggvnreesrfyloeCxfoehsnetaardondl)leafabenmnionarglmetawolagtshaeikt.irlilgedht,fodrihspulmacaenme erneat soofnshidnudrliinmgbWs, ereekdu3ceodf AWneiemka1l 3N. o. 23, Group 2 (Low dose) died during the bleed for haematology and biochemistry during Neither of the 2 deaths were considered to be related to exposure to POSF. rTehceorveerwyearneimnoaltsredautrminegntt-hreel4atwedeeekffreecctosvdeuryrinpgeritohde. 13 weeks of the treatment period or in any of the Bodyweight (Figure 1; Table 1; Appendix 3) Fbc(GCIooonormdlotnleyuotprrwpwaodreli.e4onigdsghe(w)Ht4fiiaotgwnhrhdetCredGekooarsnstoeteurod)opflra.a4tnrtsei(mF,aHtowamillgilstoehhnwbtdsoitonatdshgtyeiesw)rt1eie3fceiagwmwlhaasetssilegeksnars,eifcrcioeocofdvamunetrccrpeeteaiadrotb,emnedwieniwnnigttihtabththobteadCoriydneowyenwwdterioaefglosih.grthaaFtflsdlooortlcrlsoeotarawmgeteieapn-dtaregremdal4baastllweeaedtseeoelarlrkenitsddegurrGceeatcanriootoiemuvnrpeartilyo3ns Food consumption (Table 2; Appendix 4) ImtHTloisg1honnin3rhmioewctoglerwrryuioherfeel,pmereuaadsmtrhegsteh.okeohhcadasdswaoolineIeanunwnoetcttsIvfehthonufheteeeinmtahralxem,esnetcprpudamotmotomhli1nsLeofeia3tupssdnrlot-rteohiwwiewcawloecsotetna.eoahdnecssnwoeksodDtusilnroaenoemeoutssfwrxlfergocplpeiecoorlntwcosiorowngot.sunattunwehrspstarrhauTsabessentmsotyihwmpt4aspthaaHoemnitsarwililaoiatcpgeoarenloroshlldeestnsrfokao-edtedfcnrrmoortoloodheosodlnsacaeswdaeeti,otrncgieovnLhsccerrleeeioodobsetreennhwoyvcnossateaovuuhpnddndnemmeudossrcsrertppsitotaiwxeoathtnnniietdeoogiittastrsnnhnrsocttoeiuhdolcwbvcacenacoeychhslofrdvoueetnsHoetnhrmwihserstgaiuyerigpntonmteht4iphlcgixfs-opeeoicwdpcrntnieioiaen3eosopsnbrceundtietcyrkiom.r.oeesedranapaa.IOioslstnnttleiefsvoIdctmdseenrn.ooaxerantgabfapeltCsrltehyolbloeulesoioHdumtautnretlpcreihlsmpegsoauatg.uhatinmscreorleoioeddsnmpxuenotegfpabsisesoourselymosnfmwwrutttaabhhhepaaltdyeeeessss : 27 : MIN 313/023622 Haematology (Table 3; Appendix 5) FiannodlGlotrhwoeuinpdgif4f1e(3rHewnigceheekidssocsooefn)tsrmiedaaetlrmeesdecntoot mgbrpeoauorpef dnmowetiaotnxhircCeotolinoctugrliooclac, lyhtioemwpceoovurtenartnsnceow.esruechstaetfifseticctawllyasspigrneisfeincat nitnlyfehmigahleesr wWGddcoooeremssoreeeeup))kp,naahr1omne3otddwdelaowGaensrviregteonehrrueetpuCulhatneo4rtseronetdp(tarHhwioaniinlelegsdrdhaenwaddccneoeodrtlsnehlemsse)iinsdo(medeLneraoUrepelcdeCemysnt)toaedwiecnbicnoeetothudunonnsotlftsotassewtewfixwfseee,treicrtcrehftaeoeolllsynlrytoeaatwdtshriuieiesgnctscnigeecoidafnc4ilcosliyinawudnneeWsctreiseegkedfnbseoiuekfloliinoncfr1wage3rnleiaatncflttoyogetavrd4ielnGtorwoeywrd.etoereuerfkopaTstrihmn3oeGesft(rnrerIoeten.uadctpteoiefrvdfm4eerrem(eyHdn.aiicalgIeetnhess FrtfaadoeoltiostdfrbalofulGeieoncrewreeeoovnddfiuincdaplegfeneosuny3r4cwtt(ooaIweicnlnxrlyeteietceamernoklmlolas(oLltetegord)sseifiecbaaearaatteneelsncdosdfdoipogovghGlnsrelieooilrrf)oywui(cupBaiatpnnsh)ndgecaf3roenG1e.ld3(rlIowomwnwuatopeesiennr4mkogasc(erH4ydoetidifewagutth(reecMeeedakddo)tsomscwseoeoe)hun)ffinttereatwmesnc,bidaotwllhoveGiseotP.hrdrOyoAs,uSctpaeFwltloilis4anttchngiocd(eHausratlniaprgstteriihog(stWtthnihdceirofBaroiselcCmefao)s)nbirgciiefnnenemcitbffoiiemeancmilaseneinsagd(.clPeeaesrTte,tTba)dwheiwnneiinesatohdgest Oaintc4hoenrwsiiensettekenr-trgebrceootuwvpeerdeyniffpteherereinsoecdxeestshinaatntdhaetctoahinanseeimddeartseotdalotiigsnitcciciadalelpnastairgal nmainfeditceaornsfcnienovwteosextriiegcoatsleomdgaiiclnla, lWnsioegtenkidfoi1cs3aen-ocrreelf.aotlelodwainngd Blood chemistry (Table 4; Appendix 6) Ftsahitogtialsnlioinpfweiacdiranafngmotlrey1tG3ehrriowgruheepeemkr4asfi(onHorefidGgthrrheodiaugotphmsee3er)n(ctfIoongmltlerooprwmuaprieenddmgiawe4taeitnwhdoeaCselkoekna)sltairnoonelfd. rpGehcrooosuvppehra4yta(wsHeiitgh(hAsLdtaoPts)ies)tliecmvaealllsessiw.gneTirfehicesatnvacatielsutebicseaiflnolygr Fcsioogmlnloipfwaicriaenndgce1w3iintwhGeerCokousnpotr4fot(lr,Heaiatgmnhdednortseaeml)aaonininnleyed. amhiignhoe-rtrafnoslfleorwasineg(A4LTw)eleekvselsowf erreechoivgehreyr iwnittrheatsetdatimstaicleasl Gfcdaoroireflnofloetcurrwopoenlinnsmcvigedeaelaw1urn3eeedsrwleatwoecneteobakrtetseedoooldfofsenwethor-yeertraedotlramxaotnigeecdedonnltcaoaconsgoednicmssai(dtpLlaeaDitrmrieseHtpddi)ocwtaroltleaitvnsbhiecegleCsn.rioefwniactesraroonenlc.aelboHwlwyoaewsrsieamivtntiealraai,nrlleftodtorllefootahwrtoefidsneemggoa4rolfewustpeevssetaklosugferoosbfuooprtneshl.cyosvetThxeehreyyes mCC(Hohainolgetlhsreoswdlt,eoirtswoheli)stthlmaetvaisselteatlisstci.sawtlFicesoairlgellonswilifogiiwcnnagienfric4ceianwnbceeteerinekagbsteeaoidtnftgarmienacaetoltdeavsiiennrefyaodlltllhfotoerwerlaienGtvegrdeolug1w3proauw3spess(et.Iiknllstelroomwfeetdrreiatahtteamndenocstoenc)toroamnlspdainrGedrtroeuwaptietdh4 rCsGeirgrceonoauivtfpieincri4yannet(chHee(iCgblerheeviaendtlg)ossilaenet)vttaeraielnnsaietmdwedaeflrogserroorGufepdrbosuoucwtpheedr2seefxo(cLerosomawlfploaldtrlroaoebswaeltie)endwgfeigmt1hr3oaCulweposesneatkcrnoosdlm.oGpfartorreuedaptmt3oe(nCItno. tnetrFrmoolle,ldowiwaititenhgdso4tasetwi)setiaecnkadsl : 28 : MIN 313/023622 Tonrilgyl,yfcoelrloidweinlegvael4s wweeerke rreecdouvceerdy pinertiroedattehdergerwouepres nwoitshigsntaiftiicsatinctaldisfifgenreifnicceasncbeetwatteaeinnethdefgorrofuepms.ales 4Ocowtnheseierdkeinrtereedrc-iognvrcoeiudrypendtpaielfrfaieonrdednocwfeesnroeintostxhmiecaolbll,ioogcnihocetaml dsiciogasnlei-pfriaecrlaaantmecdee.tearnsdinvinecsotingsaitsetdenitn bWeteweeken13 tohre foslelxoewsinagnda Urinalysis (Table 5; Appendix 7) Iwtonexterierc-ogslromoguaiplcla,dlnisfoifgetnredifnoiccsaeens-rceienl.attheed paanrdaminetceornssiinstveensttigbaettewdeeinnWtheeekse1x3esa.ndNfoolnloewairneg c4ownseiedkesreodf rtoecobveeroyf Urinary pH (Appendix 10) pH values oftreated and Control animals were similar. Organ weights (Table 6; Appendix 8) A4gssstairagbwottensuielosipleftliisikutcce.taaernlerlTtcaylliotyhvsvseegiergarrdnefywitaifeftepfrieeciergrar4ethnihnottsaclwdynewetshcheeoeikwgrnseherterreegoecrxolrepfvwsoatoeaetrsretiyuigrGsrhtetarithocnsaua.iamnlptlyact3lho'sesn(iIgtnlrnHiotviefilersgirmchaiwennddetbiioagwostheethhtsed,lnseowevsxaeehdel)esjunmthsoaatefeldedtjslhuivefsaotenerIrddnbtwefGooredrmriyogbewuhodptedisiay4gtwewh(teHe.airngiegdhFhtos,Htldarliooetgismwsheti)ianc.diangoleIslnydea Lsllasuutinuagnnintnmggigsifaataiilnaccnsndaadndlabltbyflrbtryoeorsnrohingcnic4nghchihihfiwewiicwreewateeinhgeiktagihlsgnyhthstochstiosifnginnhe(mtarxeofbaprelslosmteoh.slHaauulnrteieegschoaawnndtetdortrsohebelesosrdiaaHmytfsitwigelrraheerim1g3dthaooitwsnceaeeo,dednjklutssurtsonatoeltgsfidse)taaixfcniptandeolrlsHybu4rirsgoewihn.gcenAdehifkoifissctewearoner4ftialgyrtwsehhcteosoiegfvkwhesbereooryrt.fethhreaIsscnnteaoxctvSeiosesantrtityewcrlaoltelihlrltsyeee, Kmnsdatcoiaiafcdtfldoieensiursefteinfywcnetaercweelderlnesyeficgoisenshrtsaittfgtsiheinn,semitwkfihaicihclidaegaenlshnlne.yetylaryAsdwibgfjouhetnedisiiggrtfyeihh4wcdteaweranfiofegtttlreehhykrbtagson4arddoewyjcfauweotrseeenetrkcetirtosgdhovholaketsfni,rdyeicannxoftepthnmyeoetrsrawboule1oelrse3id.rg.yahwTtwtssheefeenirgrkooehsmtetwdoatehdfrienjeueImnsxntopeateodlhersimskus.itredoeIdnp.nieaaytstheaTwothealeolenlirgidgetyheHtfrwsiiagneothdsrfeitHndhgoeingssroeehwwwdshuoeieccsrrhehee Other inter-group differences were small, not dose-related and inconsistent between the sexes. Macropathology (Table 7; Appendix 9) The macroscopic examination performed at termination revealed the following change: Liver EnonnlaerginemtheenCt wonatsroolbmsearlveemdaincr4o/p5atshaotelollgitiecaml raaltes.rats treated with 300 ppm for 4 weeks compared with A13nweenelakrsgcemomenptaroefdthweitlhivneornweaisn othbeseCrvoendtroinl r3a/t5s.male rats and 2/5 female rats treated with 300 ppm for Fotohlelorwtrienagtm4ewnte-ereklsatoefdrmecaocvroepryatnhooloengliacraglefminednintgosf. the liver was seen amongst recovery animals or any mThaecrionscciodpeniccechaanndgedsis. tribution of all the findings : were 29 considered : to fall within the background range of MIN 313/023622 Micropathology (Table 8; Appendix 9) Treatment-related findings Larynx NT10he0ecrrpeopswmise.roefnthoefivnednintrgasl wcahritcilhagweewreacsoansssiodceiraetdedtowbiethretlhaeteaddtmoitnriesattrmatieonnt ionfr3at0s0repcpemivifnogr 3103 pwpemekos.r NDeocsraogseis(popfmve)ntral cartilaTgeotal 0 0 30Males100 300 0 0 4a 0 0 3F0emale1s00 300 0 0 5b Number of larynx examined 5 5 5 5 5 5* 5 5 a* I-nc/l>u<d0e.s05o,nebs-p_opr<a0d.i0c1awniimthaFl isher's Exact Test Frceaocrletlioilvawignienggi3nt0hm0eap4lpewsmpewerekavsrieoocunoslvlyyemrryeacpregeiirvniioandlgl,yt3hr0ee0dreupcwpemdas.cnoTomheepvairidenedcnitdcoeentohcafetroencfootthveidesriyfninftrhdoeimnmgnaienincfrpeomasirsat looefsf ttphhreeevsvtieuondutysr.layl NDeocsraogseis(popfmve)ntral cartilaTgeotal 0 0 30Males100 300 0 0 4a 0 0 3F0emale1s00 300 003 Number of larynx examined 5 5 5 5 5* 5 5 5 a* -In_pc<lu0d.0e5s wonitehsFpiosrhaedri'cs aEnximacatlTest Lungs BmrtTolhuechocainccitcegsuhkrisrvoertfwinpehininhnehgndaciggecii3n/nhes0gicscsw0,iadctnewetporoeneperrtcrrmereeeudelnlaiwaamuntntecsheadduredceanrdatlwoosepceiigntthodrhhameeciegnotpeahnaosdretramfrewtodshfilaonisrsgwaieshmanctinerteoyahrditvteiatibcdohnloonvegandersotyeo3rfmfwol0oatl0heisrrnee.ipgmimcphmaomtacaAmlryalofpidtonphbojrhuoeuaasun1tigfgd3geeehdnmiwsno/afserlroleueeaeapdnktms.trgsaeryTlwceaehcthnahieeveldirivncivenekibogcnwerolgnoae1minrr3n0ecp00gmha/npipsraoecppcwdamrmftoeitw,npeiogdhrtirhtehiahndi1tgssg0ecas0lsoeli/nvnpvsinteeperopmorltalthloaa.stesr.lf : 30 : MIN 313/023622 Males Females DFsaeloovpasetmaaolglyatehra(imlcpvkpaeecomnrloa)inrpghm/asagccearstotMepMrhoeaiddSngTelieirmogsat/htaaellt 0 0000 30 100 300 0000 0000 5311b 0 0000 30 100 300 0000 0011 4220a Number of lungs examined 5 5 5 5 5 5* 5 5 a* -In_cpl<u0d.0e5s,obne-_spp<o0r.a0d1icwainthimFaislher's Exact Test Fpncorooertlvrlfoeieolwmautiseanldlgyeswtr,heiecctohe4mitvwhpieneagerbeko3dd0rwe0ycwipothepvimetghrhyebtiupratecdrlojieuonssdtsteectmdhoepnlrouvernianwgncaeiansongudgsroberorcedoocnovecvvehiredyireywinnCecmieognahotltfresors,elwpvgrerheorivsuciihpbosiurl.sietlmyyaoriefncteehdievhifniignghd3inf0og0ripmnpamfele.msTabhleuisst DFsaeloovpasetmaaolglyatehra(imlcpvkpaeecomnrloa)inrpghm/asagccearstotepMrheaidSngTlieimogst/haallt 0 011 30Males100 300 011 011 523a 0 000 3F0emale1s00 300 011 000 220 Number of lungs examined 5 5 5 5 5* 5 5 5 a* -In_cp<lu0d.0e5s wonitehsFpiosrhaedri'cs aEnximacatlTest Liver wCdafedoeemmsrnaeatigrlniaeeliss-ossrtbreroeaulccatliieataoiirtovnenhidnsoehgwpfiap3i3tt.0ho00Ic0tnyhpptepfepemammhd.ymaapnleidensrPittsthrrhtooiresapmsthweiioynanfesiennolxtdiftkiecn3enel0gydnsitptnrwopiglmoaresbt,ofull1ele0tacsh0rsteihppnepmrcpomrianed,toazoosuocernnydc3ateeh0l de0pappraiagenptamodmceawynntfetdeorrwemc1aeea3sntsastwnrboiooeclotelieiabkcdtusealdioacnrctoicmvnhailytasyyiploe.ewnsratiwtrlholiyptthhhiynea Hmbsteaeattplwieassettioecancanylhdltyeep2hha/iy5tgophcefeyrertmtreionaphlrehyasyptsercrreotecrrcoereiepvilhvaiynitneggadn3p1d0o00t0shiptepipvphmemilgy,ohwrecro3itm0lhe0pvtpaherlpeemodefncwAloaLirmtghTpe.manBroeeonnddetwyoiwinfthethiccgeoohnlntittvraroeodlrlsjsu.n.soTtteehdderlaeivtewnreawcsreocipgoshryrtesilnawt3ieo/r5ne : 31 : MIN 313/023622 Males Females DhCexyeotpnseeatnrrgditlreioonb(pgpuhptlyoamrm)hiedpzaotnoaclytaerea hPhCeyreoppnmaettrroiitnlrcooeybpntuhet lycaperinghtmeripeloantbtouclyatre MMoidSSnTTTeilliirmoooggattthhtaaaaelllltt 0 000 00 00 30 100 300 440a 505b 505b 11 00 00 00 00 00 0 000 00 00 30 100 300 000 000 523b 00 00 00 00 00 11 Number of livers examined 5 5 5 5 5 5* 5 5 a* -In_cpl<u0d.0e5s,obne-_spp<o0r.a0d1icwainthimFaislher's Exact Test Fhtbmchoyooaemdpllleyeocprwewgatnrrreioteonirpgdugilhhpowytstb.hiuaitenhdlajarut4hlslaetwreaierdfeafceelokwcivntaeetrsedremcagwofprfveooeieurcgrapthyenstd,esp.operuTaersrihmtoieccdaouihnnltitaihsrnrtoelogrylleogiingnrwoicmfuaaepsalm,lfegaaislnonedodspidrnpaeglrvesesivovoiciudwooseurilnrtsyheclyleratehtrecoeedecfiievnwriievcnivritgenheagrsts1hei30bed00i0lAsipttpayLpptmTimsotiif,ocnwrahalehl3lyple0ar0thetroeipgocaphnytemeltdyer DhmhPhNCCyeyreeouiopppdnnsmmaeezatttrrrrogboiiittnnllrreceooooeayrbb(ppnltpuuohehtapllyfyrcaapmeerrileangi)hhxvtmeerteeipperlnoaansdttbtooeiunxcclgayyamttrieenitnMMoediiSSnnTTTiilliimmoooggttthhaaaaallllltt 0 00 000 005 30Males100 300 0 00 22 55b 00 231 033 000 000 005 005 005 500* 3F0emale1s00 300 00 00 00 000 000 440a 005 005 225 a* -I_npc<lu0d.0e5s, obn-e<spp<o0ra.0d1icwaintihmFailsher's Exact Test : 32 : MIN 313/023622 Other findings MwrIiiafnnnaonaftfroiilsemadlatitnmhnegraadreolnmasttit.tbeoheadolTnetaodr;chrieryyneeaynnwsnftetxodhracoiesfevldiolaenlolbirnmdnvyutiiletralnnyeoratfgnerlaioasrlotihtfsiraweideaalnrp)tenagi,arloileermteneoap;patcciihtniloyhteachnt5erenies6lddtiileahndi(anlaeemvlcncreehearhntodlyoyeotsprpliftapeisehtkl/rrhreipeepniplvlsalyfaaoidlsfosautmiiiumonacasidh,mnalbiynnieashedgrttpryroeesiaipcrtqtltyeheaiuioirsetavekcnlumiideeannorlollgtalfoiutktio3shnets0hhefmli0iyyeslcep/tptporpteoaapmarrtpmerpbipaolsela)koean.senusaiirscnaaaSasedntwoi.donacoescnifrsiaedseitanetnnhudiaonisinswtofredlriwaididttmhaaaislnsnmturtcbaoeao(aectprnotpcermgraicoytseoehbisnveoatctleibn.ioerlaalynylll Incidental findings Aaf3ig0nlel0doipantnphgdmesrswcftirohnamiidcniphnaogarfscecdrwaowteurniaettnhecddCoanfososnirstdruteohcrlehesdhwtoitghohibcbeeher orpbefoamrndtoayoiwntfoeetxidhgiecfhooutllslaouodgawjilucisbnatlagecditkmhkgepirdoorenrutcenaoyndvcwpeera.eytihgpIohneltropingoaodyrt.tetiocdubilnaerm,extahpleeerscetreewdceeinrivetihnniogs Conclusion The following findings were related to the administration of 300 ppm of the compound: rnrllsluieaeeovrccnxtyeoogaernvvbssxele-wy-rr-cyyiftneahoionenfactffimrnfertieohcclymostoeeibsmasdaeull,peolvfalsfeieprnotvredhloeaienrmnreptgrciamnasotleoavinnccceatyrrborytotepciitlehnahhnagymtgserpee,iaxleslwo/eresbtssire.tuophalpntaanhdrloychteoheevmixpcitdakpeteelnoenndctcieiynentrggeeo/csftocporaveigtcetthmeoryerveeeinmdnrtyifadeiilznnvmoemanoflaeleaalmslreaasmrleeaasanc,drwoawipntihhdthamgiiennasccleooismmn mppbllooeertttheee rTeexhcteoenvadedrimnygianttiosthtretahsteeiodnmoiosdefzl3oe0nvaepllpsa.mreaoro1r0c0epnptrmilowbualsarashseopcaiatotecdytwe ihthypceernttrroiplohbyulianr mheapleasto, cwytiethhiynpceormtropplehtye It was not possible to identify a no effect level in this study. Cell proliferation (Appendix 11) There were no treatment-related findings. SEM and X-ray analysis of urine and bladder tissue ETlheectrreosnuMltsicorofsceoxpaemEinxaatmioninattoigoenthaenrd Xw-itRhaySMEMicropahnoatolymsiicsrroegproarpthasppaernedpedretsoenthteisdMinainthreepSocrat.nning : 33 : MIN 313/023622 Test substance and metabolite analysis PPPsld1iaFOeFv8mt,eOOSe6rpc0FSAlts0eeaidsdninmnegrtltpa/heetmnlhvceegetesLere.la.dsrdtaPtTtiflonriFhvosOe4emearr7rnSeu1ynsmw0aoinomnansfs-tpgadhtnlm/heeemoetsperLPlcrare.aOattsentSsdgPresFaeFerlndeurOduvgmefmeAertldoesscmiastfntamoremondtp8hmopli2enenl7e-snrd0saao.rnetanntyneg-uPdcg/orgFteiefen.OtdtdeehScTefltsreheaorivdenammertellptsuehnlwrveetoioesnanrlses-ra5dant3stneaoo5utgm,er0Peic1p0ndOt2l0eee,Sfdn1srFsg0.oal0/memdgv.enpetngellPoes/cmFsntteO-oLrdda.Aen1itng5eiTcen8ahtd,ne0tehyd0rfere0oolrefmwnavtgthea/nllesmisovrnLnetaoor,t The average percent recoveries standard deviations for PFOS in rat liver, serum, and urine samples were 96% 11%, 102% 14%, and 87% 11%, respectively. The average percent recoveries standard deviations for PFOA in rat liver, serum, and urine samples were 99% 9%, 105% 14%, and 110% 17%, respectively. The average percent recoveries standard deviations for POSF in rat liver, serum, and urine samples were 99% 18%, 92% 18%, and 99% 18%, respectively. : 34 : DISCUSSION MIN 313/023622 AmrCfeeodlomanmrtattearildneoli.siltsioetfTronsahlltlyeiaoo.rswensoiwnocgfiaasPt1eOa3dSrweFwdeituetochktrsiatortonesfaaittntmredfeaoontosmtadgeacnenostdnwosnfuho3mic0pch,ltii1wno0ina0csaianlsntdsGililgr3on0ausp0pptpah4praem(tnHtwaigfedohralelydoocwosoveinne)sgriad1n4e3irmwewadeelesetkkocssobrpmeercpooatdrvrueeeacdrteymdwefinotnohrt Lp4coriwevmveepireoakwurseseldoiygfwherxiettscphoowCvseeeordrneytt.rosotLtalhtuaiesnnthdgicisgfaohalllnylcdoowsnbigicrnoengnnifct4irhcawaitinwoetenleyk.igshhoitgsfhrweerceorienvehtrriygeahsteteirldlinraentmriemaaiatnelesddamhnaidglehrsefmaonradimnfeaedlmeshaiblgeuhsternreosfptoeflelcomtiwvaielnelygs Ewr1e3nictlowhavreengeroekynms.eecnointmotphfaetrheCdeowlnivtirteohrlnwmoanaseleoinbrasttehsrevaeCnddoniintnro43l//55ramtms.aalleeThrraaisttssfitanrneddainte2gd/5wwfaeistmhnao3lte0a0rpapptsparmterenfatotferodl4lwowwiteihenkg3s040cwopmepempkasrfeoodrf Hliinnairsbyfteonomtxphaanlsteehecsox.rleoossIgniwisctioahthlef fvilineuncnndotgirmnasglpfslcoearatermetliarlyteaegcadoelv,vtoeweortiylhtaheirnnmaomdameacvlrienoisdipseahtnnraacdgteeicosoon/fsmeroeppfclte3aotl0ve0tehrrepiyccpkoimnevnemoirnyafglteih/nssecfaacentomtdemarwlepediost.uhanlivdnecwoolemarrepmleseateecnrro.epcIhonavgetheryes wwnCseclcioeoxokeeimnrttterneherteleetrndyritldilahaealotistoevotnbesbingdohudrueclieelpgactifanoarrohlrcoetseheepchirtedttsheioplyvepeiwaf.neavtliactoemytorhlcdesciywdaoyttohzssteieetfoaehdpgAnhaieatLghydh-lrmepTmeepealeiearsarnntnetetriotiaelsooacntwpnrryogahsaitnnteheysilmioytpnmerneoexeinwattonteettafaedntbosde3dofor0imlmncts,iheccgaseea1lenast0oolisc0ifo.vt,iintinevhnoIariencrltlayaiydm3fn.nee0idiimmn0ndIchnzaafepiollegespbnmahsmoanetatclrdrhleefeanboadsrsttroeeeerrdagixde1lyreoc3aewsebwnewiuedtvihaleitiaghneencrhdkeghthns3tee3tah0rpip0d0neiaal0jotutmfoopbipsncpcatupeydymllmedatitense.r.lgaihhhsvnyyyTePdcppprhroeeetoewhrrrrmrrtttieeerrrsooioilngawwpppethhhheaantyydyssst Fhtbahlyoosedplolyecowrwewtnrieiottnihrpgiglhthohytbethauiiendlnajcuar4rlselataewraesdfeeafeldeiwkcvAteaeLrrsdeTwcagofeirfvnioegecuahrtplyetlssd,t.rprpeeeaamTrrtiethaoideicdnumihlntaihasgrletleoryinelgoirmngwoiuafcaelpasemsls.gafpiloneroedsdvipniorgeeusvvsiicldoyoeurnrsrecelcyelaertioeevdcfinewrgievivi1tnhe0gr0sthi3pbe0pi0lmsittpyaoptirmsot3,fic0wah0lehlppyeparhemtoigocahnyneltdyer I(tLOwAasELn)otwpaosscsoibnlseidteoredidteontbiefy30a pnpom.effect level in this study. The Lowest Adverse Effect Level : 35 : REFERENCES MIN 313/023622 Haematology APRmOJC. CTOlinR. ,PaRt.hR.,. 3a6n,d21R2A-P2A19P.ORT, S.I. (1961). The Partial Thromboplastin Time with Kaolin. pQU24IC-K4,0.A.J. (1942). In: The Haemorrhage Diseases and the Physiology of Haemostasis. ch III, Statistics AanNdGsiEmRilVarArLaLtio, sLinanbdioCloAgRy,LJSnTl.RTOhMeo,reEt.(B19io6l3.)4T:h25eo4r-e2t5ic9a.l criteria for the use ofrelative organ weights BARTLETT, M.S. (1937), Properties of sufficiency and statistical test, Proc. Roy. Soc A 160: 268 -282. DcoUnNtroNl.ETJ.TA,mC..WSta.t.(1A9s5so5c).,A50m, u1l0ti9p6l.e comparison procedure for comparing several treatments with a DUNNETT, C.W. (1964) New tables for multiple comparisons with a control. Biometrics, 20, 482. FISHER, R.A. (1973) in: (Eds). Statistical Methodsfor Research Workers. Oliver and Boyd, Edinburgh. HSTE9A7L2E5,YD, eGp.aFr.tm(1e9n9t 9o)f STthaetisFt1icsa,pHpuronxtiinmgadtoenpLarifaemSecteierntceesst.for monotonicity. Statistical Specification HSpEeAciLfiEcYat,ionGS.FT.97(2169,9D9)epTarhtemeHnt1ofaSptpartoisxtiimcsa,tHe unntoinn-gpdaornamLiefteerSctieesntcefso.r monotonicity. Statistical MproAcNedTuEreL., JN.A. m(1e9r6.3S)taCtihs-t.sqAusasr.,e5t8e,st6s9w0-i7th00o.ne degree of freedom : Extentions of the Mantel Haenszel lSeHveIRlsLoEfYa,trEea.tm(1e9n7t7, )B,ioAmneotrnic-ps,a3ra3m: 3et8r6ic- e3q8u9i.valent of Williams' test for contrasting increasing dose S14T:E56E0L-,57R2..G. D., (1959), A multiple comparison rank sum test: treatments versus control, Biometrics, WcoImLpLaIrAedMwSi,thD.aAz.er(o19d7o1s)e, Acontetrsotlf,oBridomiffeetrreicnsc,e2s7b:e1tw03ee-n1t1r7e.atment means when several dose levels are 2W8I:L5L1I9A-M53S1,.D.A. (1972), The comparison of several dose levels with a zero dose control, Biometrics, : 36 : FIGURE 1 Bodyweight - group mean values (g) MIN 313/023622 : 37 : MIN 313/023622 : 38 : TABLE 1 BODYWEIGHT - GROUP MEAN VALUES (G) Main study and recovery phase animals GROUP :i 2 COMPOUND : CONTROL EXPOSURE LEVEL(PPM): 0 30 3 -- POSF--- 100 4 300 WEEK SEX: ----------------------MALE---------------------- GROUP: 1 2 3 4 ---------------------FEMALE 12 3 -1 233 235 236 234 178 175 177 0 261 267 264 258 191 187 189 1 286 290 284 274 202 201 201 2 310 310 303 296 213 208 206 3 333 333 324 316 220 219 214 4 356 352 346 335 232 224 224 5 376 367 362 346 238 234 228 6 393 383 379 360 246 241 236 7 409 399 392 369 255 246 240 8 421 412 406 379 258 251 245 9 433 423 416 382 264 255 248 10 444 430 422 390 270 259 251 11 454 438 433 395 277 263 252 12 463 444 442 399 277 264 257 13 462 445 441 395 274 260 252 14a 479 451 455 425 291 295 257 15a 492 462 470 437 303 301 264 16a 506 470 476 454 305 306 265 17a 517 481 485 465 305 308 269 Gain * * ** Week 0-13 202 179 177 137 % of Control - 89 88 69 Weeks 13-17 50 44 47 52 % of Control - 88 94 104 83 73 - 88 27 28 - 104 * 63 76 20 74 Level of significance - all comparisons made with control * p< 0.05, ** p < 0.01 (Williams' test) Recovery animals only Print No: 0001 Printed : 24-JUN-02 Xybion protocol number : MIN 313 4 179 190 203 206 213 217 225 231 235 237 241 244 246 247 240 253 263 268 274 ** 50 60 33 122 MIN 313/023622 : 39 : Satellite study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 TABLE 1 (Bodyweight - continued) 234 -- POSF--- 30 100 300 SEX: ---------- MALE--------- GROUP: 1 4 WEEK -------- FEMALE 1 4 -1 237 237 180 176 0 263 272 190 187 1 290 292 204 193 2 316 313 209 196 3 341 332 223 204 Gain Weeks 0-3 78 60 33 16 No differences of statistical significance (p> 0.05) Print No: 0002 Printed: 24-JUN-02 Xybion protocol number: MIN 313A TABLE 2 FOOD CONSUMPTION - GROUP MEAN VALUES (G/RAT/WEEK) Main study and recovery phase animals GROUP :i 2 COMPOUND : CONTROL EXPOSURE LEVEL(PPM): 0 30 3 -- POSF--- 100 4 300 WEEK SEX: ----------------------MALE---------------------- GROUP: 1 2 3 4 ---------------------FEMALE 12 3 Print No: 0002 Printed : 24-JUN-02 Xybion protocol number : MIN 313 4 MIN 313/023622 : 40 : -1 182 194 191 186 137 141 137 142 1 171 171 172 154 133 137 132 132 2 186 184 178 172 139 137 143 129 3 195 194 192 179 144 145 141 133 4 205 199 197 188 150 147 144 131 5 206 199 196 183 150 147 145 135 6 204 199 204 190 150 147 145 136 7 203 203 203 186 149 145 144 134 8 205 202 205 191 147 147 145 133 9 203 200 201 183 147 145 142 134 10 203 202 202 187 147 141 139 131 11 206 201 202 182 147 142 140 129 12 208 200 201 181 146 142 142 130 13 194 193 190 170 139 130 130 116 14a 198 197 205 190 152 156 138 135 15a 197 197 205 196 158 160 142 141 16a 201 206 206 199 190 136 140 137 17a 203 205 205 200 147 151 138 140 Average * Weeks 1-13 199 196 196 180 145 143 141 131 % of Control - 98 98 90 - 99 97 90 Weeks 14-17 200 201 205 196 162 151 140 138 % of Control - 101 103 98 - 93 86 85 Level of significance - all comparisons made with control * p< 0.05 (Williams' test) Recovery animals only : IP : Satellite study phase GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 TABLE 2 (Food consumption - continued) 234 -- POSF--- 30 100 300 WEEK SEX: ----------------------MALE---------------------- GROUP: 1 2 3 4 ---------------------FEMALE 12 3 1 169 2 185 3 197 161 138 177 145 188 149 Print No: 0003 Printed: 24-JUN-02 Xybion protocol number: MIN 313A 4 122 131 136 MIN 313/023622 TABLE 3 Haematology - group mean values ZP Day 91 Group 1 CExopmopsuourendlevel (ppm) : Con0trol 234 --POSF------ 30 100 300 Group Hct Hb RBC Retic MCH MCHC MCV WBC N / sex L/L g/dL x1012/L % pg g/dL fL x109/L x109/L 1M Mean SD n 0.432 15.4 03.0129 03.10 8.24 2.78 18.7 35.6 52.4 12.22 2.64 03.263 03.567 03.53 03.84 03.23 43.073 23.018 2M Mean SD n 0.441 0.0127 105..370 55 08..21878 2.02 0.262 109..159 350..562 531..960 143..64677 32..25585 5555555 3M Mean SnD 4M Mean SnD 0.447 15.8 0.0202 0.74 55 0.430 15.2 05.0319 51.63 8.34 2.00 19.0 35.5 53.6 10.98 1.59 0.255 0.430 0.58 0.38 1.47 0.766 0.614 5 5+ 5 5 5 5 5* 7.83 3.44 19.5 35.4 55.1 11.71 0.90 05.816 45.050 05.32 51.39 2.18 5 51.002 05.219 Level of significance - all comparisons made with control + * p< p< 0.05 0.05 (Shirley's test) (Williams' test) MIN 313/023622 MIN 313/023622 : 43 : TABLE 3 (Haematology - continued) Day 91 Group CExopmopsuourendlevel (ppm) 12 3 4 Con0trol 30 --POSF-----100 300 Group L E B M / sex x109/L x109/L x109/L x109/L 1M Mean SD n 8.83 0.18 0.04 0.36 1.814 3 0.124 3 03.017 0.142 3 2M Mean SD n 29..60179 00..10837 00..00341 00..31046 5555 3M Mean SnD 8.92 0.20 0.03 0.20 1.216 0.076 0.013 0.027 5 5 5 5* 4M Mean 10.46 0.11 0.04 0.15 SnD 51.098 05.033 05.011 0.111 5 Level of significance - all comparisons made with control *p< * p< 0.05, 0.05 (*D*upn<ne0t.t0's1 (Williams' test) test) LUC x109/L 0.17 03*.086 00..00947 *5* 0.05 0.013 5 ** 0.06 05.031 Plt x109/L 806 2333.8 384183.4 5 851 183.1 5 1067 227.2 5 PT APTT sec sec 13.0 19.0 22 103..396 106..568 3* 3 14.2 19.0 0.46 2.98 55 13.2 18.9 05.57 35.11 TABLE 3 (Haematology - continued) : pp : Day 91 Group : 1 Compound : Exposure level (ppm) : Con0trol 234 -- POSF-- 30 100 300 Group Hct Hb RBC Retic MCH MCHC MCV WBC N / sex L/L g/dL x1012/L % pg g/dL fL x109/L x109/L 1F Mean 0.423 15.2 7.60 2.31 19.9 35.8 55.7 8.31 1.29 SD n 0.0126 0.38 0.305 0.500 0.44 0.55 0.61 2.996 0.719 333333333 2F Mean SD 00..4021512 105..144 70..62214 2.09 19.8 0.409 0.47 35.6 0.23 551..840 91..04761 1.56 0.823 n5 5 5 5 5 5 5 5 5 3F Mean SD 0.421 0.0168 105..711 70..52556 20..59371 200..078 350..681 551..953 92..84983 11..60358 n5 5 5 5 5 5 5 5 5 4F Mean 0.431 15.6 7.95 1.74 19.6 36.1 54.4 9.52 1.25 SnD 0.0109 0.29 0.333 0.372 0.70 0.31 2.20 1.461 0.493 555555555 No differences of statistical significance (p> 0.05) MIN 313/023622 MIN 313/023622 : 45 : TABLE 3 (Haematology - continued) Day 91 GCoromuppound :: Con1trol Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 G/ rsoeuxp L EBM x109/L x109/L x109/L x109/L 1F Mean SnD 62..51889 00..10526 00..00210 00..20050 3333 2F Mean 6.91 0.20 0.02 0.28 SnD 0.972 0.104 0.004 0.090 5555 3F Mean 7.38 0.16 0.03 0.22 SnD 51.748 05.090 05.019 05.100 4F Mean SD 71..80641 00..01765 00..00208 00..11073 n5555 Level of significance - all comparisons made with control *p< 0.05 (Williams' test) xL1U09C/L 00..00632 3 0.10 0.058 5 0.06 05.015 00..00263 5 x1P0l9t/L 1015181.2 3 935 48.3 5 892 585.2 1021 128.3 5 PT APTT sec sec 103..682 144..509 33 13.4 18.7 0.12 1.49 33 14.1 17.3 05*.66 51.91 12.9 0.36 181..083 55 TABLE 3 (Haematology - continued) MIN 313/023622 : 46 : Day 121 Group : 1 Compound : Exposure level (ppm) : Con0trol 234 -- POSF-- 30 100 300 Group Hct Hb RBC Retic MCH MCHC MCV WBC N / sex L/L g/dL x1012/L % pg g/dL fL x109/L x109/L 1M Mean SD n 0.410 15.4 0.0212 0.66 55 7.79 2.46 19.8 37.4 52.7 10.97 1.63 0.431 0.363 0.84 0.58 2.02 1.951 1.041 5555555 2M Mean SD n 0.395 0.0110 104..461 55 7.59 2.67 19.2 37.0 52.0 0.288 0.677 0.56 0.49 0.89 55555 92..27503 2.08 0.774 55 3M Mean SD n 00..4010382 105..223 55 70..61686 20..33685 109..289 360..837 531..905 12.27 5.446 22..66352 5555555 4M Mean SnD 0.414 15.3 0.0171 0.63 55 7.84 2.44 19.5 37.0 52.8 11.14 2.26 0.331 0.177 0.24 0.42 1.16 1.319 1.343 5555555 No differences of statistical significance (p> 0.05) MIN 313/023622 : 47 : TABLE 3 (Haematology - continued) Day 121 Group Compound Exposure level (ppm) 1 Control 2 --PO3SF------ 4 0 30 100 300 G/ rsoeuxp L EBM x109/L x109/L x109/L x109/L 1M MSeDan n 81..72004 0.15 0.041 0.03 0.018 0.25 0.068 5555 2M Mean SD n 71..29524 00..00826 00..00121 00..20099 5555 3M Mean SnD 395..10160 005..10587 005..00426 0.22 05.148 4M Mean SD n 8.37 0.18 0.03 0.19 0.705 0.104 0.011 0.086 5555 Level of significance - all comparisons made with control *p< * p< 0.05 (Williams' test) 0.05, **p< 0.01 (Dunnett's test) xL1U09C/L 0.21 0.074 5 00..10132 5 0.12 05.105 00..10244 5 x1P0l9t/L 1009 96.5 5 918225.8 5 867375.1 985 88.6 5 PT APTT sec sec 102..292 129..420 *5* 5 14.0 0.40 181..318 *4* 4* 1054*..469 1256*..308 13.7 15.7 0.50 1.45 55 TABLE 3 (Haematology - continued) MIN 313/023622 : 48 : Day 121 GCoromuppound :: Con1trol Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 G/ rsoeuxp 1F Mean SnD LH/cLt gH/dbL x1R0B1C2/L Retic % MCH pg MgC/dHLC MfCLV WBC x109/L N x109/L 004..3091102 1044..180 704..01983 2.23 04.405 2004..521 3704..536 5404..590 481..00385 1.23 04.324 2F Mean 0.397 15.0 7.45 2.00 20.2 37.8 53.3 6.04 1.18 SnD 04.0103 04.39 0.211 4 0.164 5 04.45 04.35 41.13 04*.972 04.871 3F Mean 0.373 14.1 6.96 2.24 20.2 37.8 53.5 5.46 1.07 SnD 05.0370 51.55 05.603 05.169 05.89 05.49 2.44 5 51*.892 0.444 5 4F Mean SD 00..3092127 14.7 0.98 7.24 0.247 2.23 0.325 200..388 370..567 54.2 1.56 51..27748 00..59405 n555555555 Level of significance - all comparisons made with control *p< 0.05 (Williams' test) MIN 313/023622 : 49 : TABLE 3 (Haematology - continued) Day 121 GCoromuppound :: Con1trol Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 G/ rsoeuxp L EBM x109/L x109/L x109/L x109/L 1F Mean SnD 641..33001 004..01865 004..00208 0.21 40.019 2F Mean 4.50 0.12 0.01 0.15 SnD 04*.896 04.050 04*.005 40*.074 3F Mean 4.13 0.08 0.01 0.10 SnD 51*.378 05.028 05*.007 05*.068 4F Mean SD 41..01701 00..10056 00..00104 00..00942 n5555 Level of significance - all comparisons made with control *p< 0.05 (Williams' test) xL1U09C/L 0.12 04.034 0.10 04.047 0.07 05.048 00..01505 5 x1P0l9t/L 9151040.4 840 1343*.2 683 164.1 5* 715507.6 5 PT APTT sec sec 13.2 04.46 1471..157 13.5 17.3 04.35 04.95 14.3 17.8 0.41 4 41.53 103..872 138..382 44 TABLE 4 Biochemistry - group mean values MIN 313/023622 : 50 : Day 91 GCoromuppound Exposure level (ppm) 1 Control 0 2 --PO3SF--- 4 30 100 300 G/ rsoeuxp ALP U/L ALT U/L AST U/L LDH TUo/tLal LDH1 U/L LDH2 U/L LUD/HL3 LDH4 U/L LUD/HL5 1M Mean 202 SD 40.5 44 7.7 9197.6 449107.1 2274.7 1192.9 12 9.4 2235.0 417 341.0 n 5 5* 5 5 5 5 5 5 5 2M Mean SnD 25673.2 5* 6112.3 15434.8 444 361.6 5* 5 5 287.3 5 21 12.4 5 1133.9 5 2275.8 335045.6 55 3M Mean 279 58 102 296 22 15 SnD 43.9 *5* 9.3 25.9 147.6 18.0 5555 ** 9.1 5 4M Mean 327 67 103 244 16 15 SD 67.6 12.5 13.1 59.7 6.0 3.2 n5 5 5 5 5 5 7 11 240 2.3 6.4 113.2 555 7 1.3 134.4 194 61.0 555 Level of significance - all comparisons made with control *p< 0.05, ** p< 0.01 (Williams' test) TABLE 4 (Biochemistry - continued) MIN 313/023622 : 51 : Day 91 GCoromuppound :1 : Control Exposure level (ppm) : 0 2 --PO3SF----- 4 30 100 300 G/ rsoeuxp CPK TUo/tLal SDH U/L Bili ^mol/L mUmroela/L 1M Mean 242 SD 119.0 125..367 1 0.5 n5 5 5 61..01524 5 2M Mean SnD 31261333.7 5 123..140 5* 1 0.5 5 3M Mean 202 11.5 1 SnD 78.0 5 2.67 0.5 5* 5 4M Mean 168 12.0 1 SD 53.6 1.36 0.0 n5 5 5 60..58648 5 5.80 0.254 5 60..84192 5 Level of significance - all comparisons made with control *p< 0.05 (Williams' test) ^Cmroela/tL 533.8 5 522.2 5* 48 3.6 5* 48 2.7 5 mGmloulc/L mCmhool/lL Trig mmol/L 60..47722 1.44 0.290 0.44 0.208 5* 5 5 05..54068 01..30053 00..13123 5* 5* 5 5.69 0.96 0.37 0.178 0.315 0.096 5* 5* 5 5.69 0.80 0.24 0.553 0.434 0.188 555 TABLE 4 (Biochemistry - continued) MIN 313/023622 : 52 : Day 91 Group : 1 CExopmopsuourendlevel (ppm) :: Con0trol 234 --POSF--- 30 100 300 G/rsoeuxp mmNoal/L mmKol/L mmColl/L mmCoal/L mPmhools/L Total Prot g/L 1M Mean 143 SnD 1.9 5 2M Mean 145 SnD 0.8 5 3M Mean 144 SD 1.8 n5 4M Mean SD 1431.6 n5 4.0 106 0.61 0.7 55 3.8 108 0.23 1.5 55 4.1 107 0.29 1.7 55 4.1 0.21 1061.2 55 2.68 2.02 63 0.083 0.202 1.6 555 2.69 2.05 67 0.051 0.111 4.8 5* 5 5 2.77 2.17 65 0.043 0.115 3.3 5* 5 5 20..70754 20..01309 674.7 555 MIN 313/023622 : 53 : TABLE 4 (Biochemistry - continued) Day 91 GCoromuppound Exposure level (ppm) G/rsoeuxp 1 Control 0 Alb g/L 2 -- PO3SF-- 4 30 100 300 ga/1L a2 g/L Bge/Lta 1M Mean SD 290.8 11 1.5 n44 03.5 4 2M Mean SnD 301.1 5 11 1.3 5 03.4 5 3M Mean 30 12 SnD 1.8 1.3 5* 5 4M Mean 33 12 SD 3.6 1.3 n55 3 0.4 5 3 0.4 5 Level of significance - all comparisons made with control *p< 0.05 (Williams' test) 152.1 4 152.0 5 14 1.7 5 14 1.1 5 Gagm/Lma 61.3 4 71.9 5 5 1.1 5 5 1.3 5 RAa/tGio 00..80554 4 00..81510 5 0.88 0.124 5 1.01 0.130 5 TABLE 4 (Biochemistry - continued) MIN 313/023622 : 54 : Day 91 GCoromuppound Exposure level (ppm) 1 Control 0 2 --PO3SF--- 4 30 100 300 G/ rsoeuxp ALP U/L ALT U/L AST U/L LDH TUo/tLal LDH1 U/L LDH2 U/L LUD/HL3 LDH4 U/L LUD/HL5 1F Mean 162 SD 36.3 386.0 14008.8 426462.8 2134.2 2175.9 138.4 2157.7 317985.4 n 4 4 4 4* 4 4 4 4 4* 2F Mean SnD 12356.6 5 2566.6 12089.8 217 46.6 5 5 5* 133.3 5 14 5.4 5 97.0 120.8 17513.5 5 5 5* 3F Mean 124 49 103 207 12 11 6 9 169 SnD 26.3 5 37.6 52.0 71.3 5 5 5* 1.9 5 3.5 5 2.2 5 3.2 62.5 5 5* 4F Mean 123 SD 30.4 2407.1 106 28.3 310131.9 24 22.2 22 17.9 n555555 7 2.9 13 6.4 23772.2 555 Level of significance - all comparisons made with control *p< 0.05 (Williams' test) TABLE 4 (Biochemistry - continued) : gg : Day 91 GCoromuppound Exposure level (ppm) 1 Control 0 2 --PO3SF----- 4 30 100 300 G/ rsoeuxp CPK TUo/tLal SDH U/L Bili gmol/L mUmroela/L 1F Mean 564 SD 710.1 133..462 2 0.0 n 4* 4 4 2F Mean SnD 14320.1 5* 12.4 4.03 5 30.5 5 3F Mean 132 10.7 2 SnD 35.1 5* 2.60 0.0 55 4F Mean 143 15.5 2 SD 37.4 1.54 0.4 n555 71..80077 4 70..15535 5 6.21 0.604 5 8.32 2.625 5 Level of significance - all comparisons made with control *p< 0.05, ** p< 0.01 (Williams' test) gCmroela/tL 666.6 4* 582.7 5* 55 2.7 5* 60 8.8 5 mGmloulc/L mCmhool/lL Trig mmol/L 05..92095 2.16 0.232 00..61379 444 ** 6.14 0.818 20..43373 00..40067 555 6.48 2.13 *0*.41 0.683 0.556 0.086 555 ** 5.90 1.98 0.39 0.674 0.246 0.082 555 MIN 313/023622 TABLE 4 (Biochemistry - continued) MIN 313/023622 : 56 : Day 91 Group : 1 CExopmopsuourendlevel (ppm) :: Con0trol 234 --POSF--- 30 100 300 G/rsoeuxp mmNoal/L mmKol/L mmColl/L mmCoal/L mPmhools/L Total Prot g/L 1F Mean 142 SnD 41.0 2F Mean 143 SnD 1.8 5 3F Mean 143 SD 1.5 n5 4F Mean SD 1431.3 n5 3.5 106 04.39 04.6 3.2 107 0.21 0.8 55 3.0 105 0.18 1.8 55 30..424 1050.9 55 2.81 1.60 70 04.064 04.292 41.5 2.84 1.50 75 0.112 0.118 3.0 555 2.75 1.58 70 0.079 0.094 4.0 5 5 5* 20..70928 01..16148 763.6 555 MIN 313/023622 : 57 : TABLE 4 (Biochemistry - continued) Day 91 GCoromuppound Exposure level (ppm) G/rsoeuxp 1 Control 0 Alb g/L 2 -- PO3SF-- 4 30 100 300 ga/1L a2 g/L Bge/Lta 1F Mean SD 37 1.0 100.5 n44 4 0.6 4 2F Mean SnD 403.6 5 11 0.7 5 4 0.8 5 3F Mean 37 10 SnD 2.3 *5* 0.5 *5* 4F Mean 42 12 SD 2.0 0.5 n55 4 0.5 5 3 0.5 5 Level of significance - all comparisons made with control ** p< 0.01 (Williams' test) 14 0.5 4 14 0.8 5 14 0.5 5 13 1.8 5 Gagm/Lma 61.0 4 72.0 5 6 1.5 5 6 1.6 5 RAa/tGio 01..00185 4 01..11560 5 1.13 0.057 5 1.21 0.099 5 TABLE 4 (Biochemistry - continued) MIN 313/023622 : 58 : Day 121 Group Compound 1 Control 2 --PO3SF------ 4 Exposure level (ppm) : 0 30 100 300 G/ rsoeuxp ALP U/L 1M Mean 182 SD 25.4 n5 2M Mean 234 SD 34.4 n5 3M Mean SD 14985.3 n 5* 4M Mean 244 SnD 445.0 ALT AST LDH LDH1 LDH2 LDH3 LDH4 LDH5 U/L U/L Total U/L U/L U/L U/L U/L U/L 11 11 14 19 125 40 74 180 1.5 3.2 8.6 3.2 19.8 35.7 75+.5 285.0 5 14 5 9 5 5 55 12 122 5160.4 10109.4 162 57.2 3.8 5 2.2 5 1.6 5 3.8 51.7 55 5 5+ 5 15 11 5 14 108 4190.2 875.3 14538.3 35.0 25.9 25.9 75.2 375.5 5+ 5+ 5 85 118 199 17 7.3 15 3.4 18.4 19 141 7.4 32.8 625.2 525.6 485.2 5 5 5 5 5 Level of significance - all comparisons made with control * + pp << 0.05 0.05 (Williams' test) (Shirley's test) MIN 313/023622 : 59 : TABLE 4 (Biochemistry - continued) Day 121 GCoromuppound Con1trol Exposure level (ppm) : 0 2 --PO3SF------ 4 30 100 300 G/rsoeuxp TCUoP/tLKal SUD/LH ^mBoilli/L mUmroela/L ^Cmroeal/tL 1M Mean 240 12.3 2 SD n 1465.1 35.04 05.5 4.90 49 05.266 51.9 2M Mean 153 13.6 2 SD 45.5 1.68 0.5 n5 5 5 5.93 49 0.685 3.6 55 3M Mean 183 12.9 1 SnD 116.5 5 4.77 0.8 55 5.71 0.777 492.2 55 4M Mean 293 19.0 1 SnD 1159.0 95.61 05.4 5.38 48 05.600 25.9 Level of significance - all comparisons made with control * + pp<< 0.05 0.05 (Williams' test) (Shirley's test) mGmloulc/L mCmhool/lL mTmroigl/L 6.23 1.67 0.44 05.700 05*.423 05.129 7.14 1.09 0.38 0.945 0.302 0.096 5 5* 5 6.56 0.780 01..21394 0.38 0.058 5 5* 5 5.46 1.37 0.33 05.372 05.131 05.103 TABLE 4 (Biochemistry - continued) MIN 313/023622 : 60 : Day 121 Group : 1 Compound : Control Exposure level (ppm) : 0 G/rsoeuxp mmNoal/L 2 -- PO3SF-- 4 30 100 300 K mmol/L mmColl/L mmCoal/L mPmhools/L Total Prot g/L 1M Mean 142 SD n 05.5 3.8 102 05.30 05.7 2M Mean 142 SD 1.1 n5 3.9 103 0.13 0.8 55 3M Mean 142 SD 0.9 n 5* 4M Mean 144 SnD 05.7 30..830 1030.8 5 5* 3.9 103 05.08 05.0 Level of significance - all comparisons made with control *p< * p< 0.05 0.05 (Williams' (Dunnett's test) test) 2.60 1.79 66 05.039 05.092 51.8 2.61 1.71 63 0.036 0.158 1.5 5 5 5* 20..50539 01..17431 612.9 555 2.64 1.79 66 05.049 05.112 25.3 1 9: : TABLE 4 (Biochemistry - continued) Day 121 GCoromuppound Exposure level (ppm) G/rsoeuxp 1 Control 0 Alb g/L 2 -- PO3SF-- 4 30 100 300 ga/1L a2 g/L Bge/Lta 1M Mean SD 311.3 12 0.9 n 5* 5 2M Mean SnD 291.8 *5* 101.0 5 3M Mean 28 10 SnD 0.7 1.1 55 05.4 5 51.5 5 4 0.4 5 4M Mean 31 12 SD 1.8 0.9 n55 5 0.4 5 Level of significance - all comparisons made with control * p< 0.05, **p< 0.01 (Dunnett's test) 14 0.8 5 151.3 5 14 1.1 5 14 0.8 5 Gagm/Lma 4 1.5 5 05.8 5 5 1.6 5 5 0.8 5 RAa/tGio 00..90280 5 00..81412 5 0.84 0.059 5 0.89 0.070 5 MIN 313/023622 TABLE 4 (Biochemistry - continued) MIN 313/023622 : 62 : Day 121 GCoromuppound 1 Control 2 --PO3SF------ 4 Exposure level (ppm) : 0 30 100 300 G/ rsoeuxp ALP U/L 1F Mean SD 12167.8 n4 2F Mean SnD 9258.9 5 3F Mean 104 SnD 13.4 5 4F Mean 112 SD 22.3 n5 ALT U/L AST U/L LDH TUo/tLal LDH1 U/L LDH2 U/L LUD/HL3 LDH4 U/L LUD/HL5 9 8 7 10 133 6607.5 112193.0 210693.1 54.4 4.2 4 54.2 74.7 154.4 4 444 13 10 10 21 303 3576.7 124 94.1 325166.3 25.3 55.8 45.7 175.8 1953.1 555 38 84 252 15 9 6 17 204 5.1 5.1 2.6 13.5 123.7 12.7 19.9 147.5 5 5 5 5 5 5 5 5 14 11 6 16 201 44 11.7 86 17.7 248 121.3 6.3 5 4.8 5 2.6 5 6.6 121.6 55 555 Level of significance - all comparisons made with control *p< 0.05, ** p< 0.01 (Williams' test) MIN 313/023622 : 63 : TABLE 4 (Biochemistry - continued) Day 121 GCoromuppound :: 1 Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 G/ rsoeuxp CPK TUo/tLal SDH U/L Bili ^mol/L mUmroela/L ^Cmroeal/tL 1F Mean 104 SD 33.3 1190..166 30.6 n 4 4 4* 2F Mean SnD 18760.5 5 166..190 5 2 0.5 5* 3F Mean 285 13.1 2 SnD 368.6 5 2.52 0.0 55 ** 4F Mean 150 23.0 1 SD 58.9 19.61 0.4 n5 5 5 60..88582 593.2 44 60..27370 573.3 55 6.13 57 0.375 4.9 55 61..82726 59 6.0 55 Level of significance - all comparisons made with control *p< 0.05, ** p< 0.01 (Williams' test) mGmloulc/L mCmhool/lL Trig mmol/L 71..30375 20..75163 00..53356 444 70..19646 20..37922 00..50183 555 7.08 1.83 0.39 0.807 0.890 0.125 555 71..43711 2.18 0.709 00..14171 555 TABLE 4 (Biochemistry - continued) Day 121 GCoromuppound :: 1 Control Exposure level (ppm) : 0 G/rsoeuxp mmNoal/L 2 -- PO3SF-- 4 30 100 300 K mmol/L mmColl/L mmCoal/L mPmhools/L Total Prot g/L MIN 313/023622 : 64 : 1F Mean SD 140 1.3 n 4* 2F Mean 142 SnD 0.9 5* 3F Mean 142 SnD 1.1 5 ** 4F Mean 143 SD 1.5 n5 30..314 1011.0 44 30..432 102 1.3 5 5* 3.3 103 0.22 0.9 55 ** 3.6 104 0.19 1.9 55 Level of significance - all comparisons made with control *p< 005, ** p< 0.01 (Williams' test) 20..07983 01..25187 741.3 444 2.74 0.086 1.32 0.157 714.0 555 2.64 1.42 70 0.089 0.227 4.9 555 2.71 1.63 71 0.080 0.369 2.5 555 MIN 313/023622 : 65 : TABLE 4 (Biochemistry - continued) Day 121 Group CExopmopsuourendlevel (ppm) G/rsoeuxp 1 Con0trol Alb g/L 234 -- POSF-- 30 100 300 ga/1L ga/2L Bge/Lta 1F Mean 41 SnD 34.1 904.8 4 04.0 2F Mean 39 SD 2.5 91.2 4 0.5 n555 3F Mean 38 SD 2.3 101.1 n55 3 0.5 5 4F Mean SD 390.9 91.5 4 0.5 n555 No differences of statistical significance (p> 0.05) 14 04.5 14 0.8 5 14 0.5 5 14 1.0 5 Gagm/Lma 045.8 5 1.3 5 62.2 5 51.4 5 A/G Ratio 1.29 04.171 1.20 0.102 5 1.16 0.096 5 1.21 0.060 5 TABLE 5 Urinalysis - group mean values 99 Day 91 GCoromuppound :: 1 Control Exposure level (ppm) : 0 G/rsoeuxp Vmoll 2 -- PO3SF-- 4 30 100 300 PH SG g/L Pgr/Lot mUm-Nola/L U-K mmol/L mUm-oCl/lL 1M Mean SD 7.2 3.55 70..343 10358.5 n5 5 5 2M Mean SnD 25..031 5 70..327 1044 11.8 55 3M Mean SnD 4M Mean SD n 7.2 6.9 1036 1.49 0.33 5.8 5 *5* *5* 4.0 6.6 1058 1.59 0.15 13.8 555 Level of significance - all comparisons made with control *p< 005, ** p< 0.01 (Williams' test) 00..93462 755..271 55 01..30105 4865..788 55 0.85 68.3 0.096 25.17 55 1.15 101.9 0.366 62.90 55 20409..915 5 247.7 44.38 5 195.3 40.74 5* 268.7 53.63 5 8186..203 5 3807..199 5 77.2 19.32 5 94.0 27.71 5 MIN 313/023622 TABLE 5 (Urinalysis - continued) MIN 313/023622 : 67 : Day 91 GCoromuppound :: 1 Control Exposure level (ppm) : 0 G/rsoeuxp Vmoll 2 -- PO3SF-- 4 30 100 300 pH SG g/L Pgr/Lot mUm-Nola/L U-K mmol/L mUm-oCl/lL 1F Mean SD 42..356 60..618 10368.4 n555 00..01691 2886..975 14509..422 555 2883..460 5 2F Mean SnD 3F Mean SnD 4F Mean SD n 4.2 1.26 60..730 10366.1 555 2.8 6.4 1054 0.91 0.16 9.8 5 5 *5* 2.3 0.61 6.6 0.38 102628.3 555 0.21 0.053 81.2 23.18 12567..405 5 5 5* 7192..741 5 0.25 87.4 242.3 0.041 18.34 30.20 *5* 5 *5* 93.3 21.99 5 0.31 92.9 310.0 112.2 0.083 35.86 96.56 31.87 5555 Level of significance - all comparisons made with control *p< 005, ** p< 0.01 (Williams' test) TABLE 5 (Urinalysis - continued) MIN 313/023622 : 68 : Day 121 GCoromuppound :: 1 Control Exposure level (ppm) : 0 G/rsoeuxp Vmoll 2 -- PO3SF-- 4 30 100 300 pH SG g/L Pgr/Lot mUm-Nola/L U-K mmol/L mUm-oCl/lL 1M Mean SD n 2M Mean SnD 3M Mean SnD 4M Mean SD n 47..135 70..136 10304.7 555 6.2 1.55 70..007 1042 9.6 5 5* 5* 5.8 6.7 1048 3.14 0.18 15.1 5 *5* 5* 5.5 2.03 60..612 104182.7 555 00..82714 506..239 13585..198 5 *5* 5 01..43908 92.2 19.26 209.4 61.83 555 ** 1.15 97.4 218.5 0.286 28.33 63.78 555 ** 1.02 69.0 231.4 0.161 12.55 61.31 555 Level of significance - all comparisons made with control *p< 005, ** p< 0.01 (Williams' test) 5121..004 5 7292..280 5 71.3 21.21 5 6171..461 5 TABLE 5 (Urinalysis - continued) Day 121 Group : 1 CExopmopsuourendlevel (ppm) :: Con0trol G/rsoeuxp Vmoll 234 --POSF---- 30 100 300 pH SG Prot g/L g/L Nma mTootlal KmTmootal l Cml Tmootlal 69 1F Mean SnD 424..038 604..115 1041 64.0 2F Mean 4.7 6.2 1039 SD 0.79 0.20 1.8 n555 3F Mean 2.7 6.1 1049 SD 1.10 0.13 10.8 n555 4F Mean SD 31..403 60..121 10469.6 n555 No differences of statistical significance (p> 0.05) 400..20759 004..21328 004..63612 004..11191 0.21 0.32 0.85 0.32 0.043 0.095 0.181 0.154 5555 0.24 0.14 0.57 0.16 0.078 0.132 0.084 0.117 5555 00..20767 0.24 0.061 00..60970 00..10942 5555 MIN 313/023622 TABLE 5 (Urinalysis - continued) Day 121 Group : 1 CExopmopsuourendlevel (ppm) :: Con0trol Group U-Na / sex mmol/L 234 -- POSF-- 30 100 300 U-K U-Cl mmol/L mmol/L MIN 313/023622 : 70 : 1F Mean 58.8 177.6 49.3 SD n 94.28 34.12 4 74.70 2F Mean 67.9 181.2 66.8 SnD 158.51 335.92 285.80 3F Mean SD 47.3 239.0 26.34 87.36 2542..148 n5 5 5 4F Mean 72.1 218.5 57.3 SnD 16.33 57.82 55 7.77 5 Main study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 U) 1 N> O1 1 1 1 TABLE 6 Organ weights - group mean values (g) 34 -- POSF-------- 100 300 Print No: 0021 Printed: 24-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 71 : SEX: GROUP: NUMBER : 5 ABSOLUTE VALUES ---2 --5 ---3-- 5 ---4-- 5 TERMINAL BODY WEIGHT (g) N MEAN sd :5 : 452.6 : 30.2 5 449.7 43.0 5 440.5 25.3 5 371.4 26.9 BRAIN N MEAN sd : : : 5 2.02 0.08 5 2.03 0.09 5 1.98 0.09 5 2.00 0.07 ADRENALS N MEAN sd : : : 5 0.061 0.016 5 0.054 0.008 5 0.056 0.007 5 0.058 0.009 HEART N MEAN sd : : : 5 1.460 0.213 5 1.377 0.184 5 1.380 0.161 5 1.327 0.217 KIDNEYS N MEAN sd : : : 5 2.59 0.23 5 2.61 0.26 5 2.78 0.34 5 2.45 0.25 Level of significance - all comparisons made with control *p< 0.05, ** p< 0.01 (Williams' test) BODYWEIGHT ADJUSTED VALUES ---2--- ---3-- ---4-- 5555 5 1.97 5 0.056 5 1.348 5 2.42 BRAIN 5 1.99 5 1.96 ADRENALS 5 0.050 5 0.054 HEART 5 1.279 5 1.325 KIDNEYS * 55 2.45 2.70 5 2.10 5 0.069 5 1.592 ** 5 2.86 Main study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 U) 1 N> O1 1 1 1 TABLE 6 (Organ weights - continued) 34 -- POSF-------- 100 300 Print No: 0021 Printed: 24-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 72 : SEX: GROUP: NUMBER : 5 ABSOLUTE VALUES ---2 --5 ---3-- 5 ---4-- 5 LIVER N MEAN sd : : : 5 14.82 2.02 5 14.57 1.94 5 16.27 1.61 5 18.41 1.78 LUNGS & BRONCHI N MEAN sd : : : 5 1.520 0.115 5 1.468 0.149 5 1.592 0.264 5 1.979 0.152 Level of significance - all comparisons made with control * p< 0.05, ** p< 0.01 (Williams' test) BODYWEIGHT ADJUSTED VALUES ---2--- ---3-- ---4-- 5555 5 13.70 LIVER * 5 13.59 5 15.71 ** 5 21.07 5 1.429 LUNGS & BRONCHI 5 1.388 5 1.547 ** 5 2.194 Main study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 TABLE 6 (Organ weights - continued) 234 -- POSF--- 30 100 300 Print No: 0022 Printed: 24-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 73 : SEX: GROUP: NUMBER: ABSOLUTE VALUES ---------------- FEMALE--------------- -- 1 --- 2 ---3 ---4 4555 TERMINAL BODY WEIGHT (g) N MEAN sd :4 : 265.3 : 7.7 5 242.8 14.5 5 256.7 31.6 5 241.0 15.3 BRAIN N MEAN sd : : : 4 1.92 0.10 5 1.86 0.03 5 1.88 0.07 5 1.92 0.09 ADRENALS N MEAN sd : : : 4 0.059 0.010 5 0.066 0.012 5 0.067 0.007 5 0.064 0.009 HEART N MEAN sd : : : 4 0.985 0.052 5 0.971 0.073 5 0.943 0.067 5 0.920 0.167 KIDNEYS N MEAN sd : : : 4 1.62 0.18 5 1.69 0.11 5 1.76 0.12 5 1.64 0.23 No differences of statistical significance (p> 0.05) BODYWEIGHT ADJUSTED VALUES ---------------- FEMALE--------------- -- 1--- -- 2--- -- 3 ---4 45 5 5 4 1.89 BRAIN 5 1.87 5 1.87 5 1.94 Main study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 TABLE 6 (Organ weights - continued) 234 -- POSF--- 30 100 300 Print No: 0022 Printed: 24-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 74 : SEX GROUP NUMBER ABSOLUTE VALUES ---2--- ---3-- ---4-- 4555 LIVER N MEAN sd 4 8.88 0.75 5 8.54 0.79 5 9.86 1.31 5 12.24 1.43 LUNGS & BRONCHI N MEAN sd 4 1.170 0.049 5 1.098 0.050 5 1.214 0.150 5 1.597 0.160 Level of significance - all comparisons made with control * p< 0.05, ** p< 0.01 (Williams' test) BODYWEIGHT ADJUSTED VALUES ---2--- ---3--- ---4-- 4555 4 8.29 LIVER * 5 8.86 5 9.62 ** 5 12.64 4 1.116 LUNGS & BRONCHI 5 1.127 5 1.193 ** 5 1.632 Recovery phase animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 TABLE 6 (Organ weights - continued) 234 -- POSF--- 30 100 300 Print No: 0014 Printed: 25-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 75 : SEX: GROUP: NUMBER: ABSOLUTE VALUES ----------------- MALE---------------- -- 1 --- 2 ---3 ---4 5 555 TERMINAL BODY WEIGHT (g) N MEAN sd :5 : 482.5 23.2 5 457.7 39.2 5 469.6 43.5 5 442.9 33.7 BRAIN N MEAN sd : : : 5 2.11 0.09 5 2.13 0.09 5 2.08 0.08 5 2.05 0.12 ADRENALS N MEAN sd : : : 5 0.057 0.010 5 0.052 0.008 5 0.052 0.004 5 0.050 0.007 HEART N MEAN sd : : : 5 1.471 0.150 5 1.449 0.156 5 1.513 0.143 5 1.546 0.226 KIDNEYS N MEAN sd : : : 5 2.80 0.06 5 2.97 0.25 5 2.89 0.41 5 2.86 0.26 Level of significance - all comparisons made with control * p< 0.05 (Williams' test) BODYWEIGHT ADJUSTED VALUES ---------------- MALE----------------- -- 1--- -- 2--- -- 3 ---4 55 5 5 5 2.68 KIDNEYS 5 3.00 5 2.85 * 5 2.98 Recovery phase animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 U) 1 N> O1 1 1 1 TABLE 6 (Organ weights - continued) 34 -- POSF-------- 100 300 Print No: 0014 Printed: 25-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 76 : SEX: GROUP: NUMBER : 5 ABSOLUTE VALUES ---2 --5 ---3-- 5 ---4-- 5 LIVER N MEAN sd : : : 5 12.14 0.67 5 12.48 1.43 5 13.94 1.72 5 15.53 1.18 LUNGS & BRONCHI N MEAN sd : : : 5 1.472 0.088 5 1.467 0.057 5 1.445 0.141 5 1.616 0.144 Level of significance - all comparisons made with control ** p< 0.01 (Williams' test) BODYWEIGHT ADJUSTED VALUES ---2--- ---3-- ---4-- 5555 5 11.62 LIVER ** 5 12.62 5 13.76 ** 5 16.07 5 1.426 LUNGS & BRONCHI 5 1.480 5 1.429 ** 5 1.665 Recovery phase animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 U) 1 N> O1 1 1 1 TABLE 6 (Organ weights - continued) 34 -- POSF-------- 100 300 Print No: 0015 Printed: 25-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 77 : SEX: GROUP: NUMBER : 4 ABSOLUTE VALUES ---2 --5 ---3-- 5 ---4-- 5 TERMINAL BODY WEIGHT (g) N MEAN sd :4 : 291.4 : 18.1 5 291.5 22.0 5 258.0 11.2 5 260.9 23.9 BRAIN N MEAN sd : : : 4 1.97 0.05 5 2.05 0.09 5 1.92 0.07 5 1.93 0.06 ADRENALS N MEAN sd : : : 4 0.073 0.006 5 0.071 0.011 5 0.068 0.009 5 0.063 0.007 HEART N MEAN sd : : : 4 1.142 0.049 5 1.030 0.151 5 0.987 0.097 5 0.925 0.051 KIDNEYS N MEAN sd : : : 4 1.88 0.09 5 1.90 0.21 5 1.77 0.11 5 1.67 0.18 No differences of statistical significance (p> 0.05) BODYWEIGHT ADJUSTED VALUES ---2--- ---3-- ---4-- 4555 4 1.94 4 0.069 4 1.105 4 1.79 BRAIN 5 2.02 5 1.95 ADRENALS 5 0.066 5 0.073 HEART 5 0.993 5 1.024 KIDNEYS 5 1.81 5 1.85 5 1.96 5 0.067 5 0.955 5 1.74 Recovery phase animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 TABLE 6 (Organ weights - continued) 234 -- POSF--- 30 100 300 Print No: 0015 Printed: 25-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 78 : SEX: GROUP: NUMBER : 4 ABSOLUTE VALUES ---2 --5 ---3-- 5 ---4-- 5 LIVER N MEAN sd : : : 4 8.99 0.94 5 8.80 0.67 5 8.44 0.46 5 9.78 1.11 LUNGS & BRONCHI N MEAN sd : : : 4 1.290 0.067 4 1.200 0.072 5 1.089 0.072 5 1.187 0.074 Level of significance - all comparisons made with control ** p< 0.01 (Williams' test) BODYWEIGHT ADJUSTED VALUES ---2--- ---3-- -- 4--4555 4 8.45 LIVER 5 8.23 5 9.00 ** 5 10.25 4 1.245 LUNGS & BRONCHI 5 1.151 5 1.131 5 1.221 MIN 313/023622 : 79 : Satellite study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 TABLE 6 (Organ weights - continued) 234 -- POSF--- 30 100 300 SEX: GROUP: NUMBER: ABSOLUTE VALUES ------- M A L E ------- 55 BODYWEIGHT ADJUSTED VALUES -------- MALE------- 55 TERMINAL BODY WEIGHT (g) N MEAN sd :5 : 332.8 : 30.3 5 317.9 22.1 ADRENALS ADRENALS N MEAN sd : : : 5 0.053 0.015 5 0.056 0.009 5 0.050 5 0.059 BRAIN N MEAN sd : : : 5 1.94 0.12 5 1.97 0.06 HEART HEART N MEAN sd : : : 5 1.284 0.223 5 1.304 0.154 5 1.235 5 1.353 KIDNEYS KIDNEYS N MEAN sd : : : 5 2.32 0.23 5 2.33 0.19 5 2.27 5 2.38 No differences of statistical significance (p> 0.05) Print No: 0005 Printed: 24-JUN-02 Xybion protocol number: MIN 313A MIN 313/023622 : 80 : Satellite study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 2 30 TABLE 6 (Organ weights - continued) 34 100 300 SEX: GROUP: NUMBER : ABSOLUTE VALUES ------- MALE-------- 1--- -- 4 55 BODYWEIGHT ADJUSTED VALUES -------- MALE------ --- 1 --- 4 55 N MEAN sd : : : LIVER 5 9.62 1.12 5 12.71 0.97 LIVER +++ 55 9.36 12.98 N MEAN sd : : : LUNGS & BRONCHI 5 1.251 0.178 5 1.705 0.104 LUNGS & BRONCHI +++ 55 1.225 1.731 Level of significance - all comparisons made with control +++ p< 0.001 (Student's 't' test) Print No: 0005 Printed: 24-JUN-02 Xybion protocol number: MIN 313A MIN 313/023622 : 81 : Satellite study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 TABLE 6 (Organ weights - continued) 234 -- POSF--- 30 100 300 SEX: GROUP: NUMBER : ABSOLUTE VALUES -----FEMALE------- 55 BODYWEIGHT ADJUSTED VALUES ------- F E M A L E ------- 55 TERMINAL BODY WEIGHT (g) N MEAN sd :5 : 212.8 : 16.1 5 194.6 7.2 N MEAN sd : : : ADRENALS 5 0.066 0.012 5 0.069 0.010 ADRENALS + 55 0.060 0.076 BRAIN N MEAN sd : : : 5 1.84 0.08 5 1.79 0.06 HEART HEART N MEAN sd : : : 5 0.909 0.100 5 0.827 0.027 5 0.869 5 0.867 KIDNEYS N MEAN sd : : : 5 1.54 0.11 5 1.48 0.08 Level of significance - all comparisons made with control + p< 0.05 (Student's 't' test) Print No: 0006 Printed: 24-JUN-02 Xybion protocol number: MIN 313A MIN 313/023622 : 82 : Satellite study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 2 30 TABLE 6 (Organ weights - continued) 34 100 300 SEX: GROUP: NUMBER: ABSOLUTE VALUES -----FEMALE-------- 1--- -- 4 55 BODYWEIGHT ADJUSTED VALUES ------- FEMALE----- --- 1 --- 4 55 N MEAN sd 5 7.20 0.62 LIVER + 5 7.93 0.27 N MEAN sd LUNGS 5 1.040 0.086 & BRONCH ++ 5 1.334 0.105 Level of significance - all comparisons made with control + p< 0.05, ++ p< 0.01 (Student's 't' test) Print No: 0006 Printed: 24-JUN-02 Xybion protocol number: MIN 313A TABLE 7 Macroscopic pathology - group distribution MIN 313/023622 : 83 : Main study animals GROUP COMPOUND : : EXPOSURE LEVEL(PPM): i 0CONTROL 23 4 100---POSF--- 30 300 Print No: 0025 Printed: 25-JUN-02 Xybion protocol number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D ---- SEX: -------MALE------- ------FEMALE-----GROUP: -1- -2- -3- -4- -1- -2- -3- -4- ORGAN AND KEYWORD(S) OR PHRASE NUMBER: 5 5 5 5 4 5 5 5 ** TOP OF LIST ** KIDNEYS .................................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 0 0 0 0 0 1 0 1PELVIC DILATION LIVER ...................................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 1 1 1 1 0 0 0 1MEDIAN CLEFT PALE AREA(S) 0 0 0 0 0 0 2ENLARGED 3 LUNGS & BRONCHI ........................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 1 1 1 0 0 0 0 0CONGESTED 0 0 0 0 0 0 0INCOMPLETE COLLAPSE 3 0 0 0 0 0 0 0 1DARK AREA(S) LN MANDIBULAR .............................. ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 1 1 0 0 0 1 1 1ENLARGED 2 1 1 2 0 0 0 1CONGESTED MISCELLANEOUS .............................. ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 0 1 1 0 0 1ANIMAL THIN 33 0 0 0 0 1 0 0 0FUR STAINING 0 0 0 0 0 0 0 1FUR BADLY GROOMED PREPUTIAL GLANDS .......................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 0 1 0 0 0 0 0 0ABSCESS(ES) 0 0 0 0PROSTATE ................................... ........... NUMBER EXAMINED: 5 5 5 5 0 1 0 0 0 0 0 0ABSCESS(ES) SKIN ....................................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 0 1 1 0 1 1 1HAIRLOSS 3 0 1 0 0 0 0 0 0SCAB (S) Main study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i 0CONTROL ORGAN AND KEYWORD (S) OR PHRASE TABLE 7 (Macroscopic pathology - continued) 23 4 100-- POSF--- 30 300 Print No: 0025 Printed: 25-JUN-02 Xybion protocol number: MIN 313 --- N U M B E R - O F - A N I M A L S A F F E C T E D -- SEX: ---MALE--- --- --- --FEMALE-- GROUP: -1- -2- -3- -4- -1- -2- -3- -4- NUMBER: 5 5 5 5 4 5 5 5 MIN 313/023622 : 84 : STOMACH .................................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 1 0 0 1 0 1 1 0ANTRUM WHITE NODULE(S) 0 0 0 1 0 0 0 0CORPUS WHITE NODULE(S) 0 0 0 0 0 0 0 1FORESTOMACH DEPRESSION(S) TAIL ....................................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 0 0 0 0 0 0 1 1SWELLING(S) THYMUS ..................................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 0 0 0 0 0 1 0 0DARK 0 0 0 0UTERUS ..................................... ........... NUMBER EXAMINED: 0 0 0 0 0 1 2FLUID DISTENSION 4555 3 ** END OF LIST ** TABLE 7 (Macroscopic pathology - continued) MIN 313/023622 : 85 : Recovery phase animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0016 Printed: 25-JUN-02 Xybion protocol number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D ---- SEX: -------MALE------- ------FEMALE GROUP: -1- -2- -3- -4- -1- -2- -3- -4- ORGAN AND KEYWORD(S) OR PHRASE NUMBER: 5 5 5 5 4 5 5 5 ** TOP OF LIST ** KIDNEYS .................................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 PELVIC DILATION 00000100 LIVER ...................................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 MEDIAN CLEFT PALE A R E A (S) 00010000 LOBULAR PATTERN ACCENTUATED 00010000 EPIDIDYMIDES ............................... ........... NUMBER EXAMINED: 5 5 5 5 0 0 0 0 SWELLING(S) 00100000 LN MANDIBULAR .............................. ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 ENLARGED 00101100 CONGESTED 00000002 MISCELLANEOUS .............................. ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 ANIMAL THIN 00010000 SKIN ....................................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 HAIRLOSS 22043210 SCAB (S) 01000000 STOMACH .................................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 ANTRUM WHITE NODULE(S) 02100020 URETERS .................................... ........... NUMBER EXAMINED: 5 5 5 5 4 5 5 5 DISTENDED 00000100 UTERUS ..................................... ........... NUMBER EXAMINED: 0 0 0 0 4 5 5 5 FLUID DISTENSION 00000221 ** END OF LIST ** TABLE 7 (Macroscopic pathology - continued) MIN 313/023622 : 86 : Satellite study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0007 Printed: 24-JUN-02 Xybion protocol number: MIN 313A -- N U M B E R - O F - A N I M A L S - A F F E C T E D ---- SEX: -- MALE-- -FEMALEGROUP: -1- -4- -1- -4- ORGAN AND KEYWORD (S) OR PHRASE NUMBER: 5 5 5 5 ** TOP OF LIST ** KIDNEYS ............................ .................... NUMBER EXAMINED: 5 5 5 5 PELVIC DILATION 0200 LIVER .............................. .................... NUMBER EXAMINED: 5 5 5 5 MEDIAN CLEFT PALE A R E A (S) 0123 ENLARGED 0400 LN MANDIBULAR ...................... .................... NUMBER EXAMINED: 5 5 5 5 ENLARGED 0030 LUNGS & BRONCHI .................... .................... NUMBER EXAMINED: 5 5 5 5 PALE A R E A (S) 0010 CONGESTED 0001 TAIL .................................................... NUMBER EXAMINED: 5 5 5 5 PUSTULE (S) 0020 UTERUS ............................. .................... NUMBER EXAMINED: 0 0 5 5 FLUID DISTENTION 0001 ** END OF LIST ** TABLE 8 Microscopic pathology - group distribution MIN 313/023622 : 87 : Main study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0029 Printed: 18-SEP-02 Protocol Number: MIN 313 --- N U M B E R - O F - A N I M A L S SEX: --- MALE-- --- --- --FEMALE-- GROUP: -1- -2- -3- -4- -1- -2- -3- -4- o r g a n /t i s s u e e x a m i n e d NUMBER: 5 5 5 5 4 5 5 5 ** TOP OF LIST ** HEART .................................................. . NUMBER EXAMINED: 5 0 0 5 4 0 0 5 NOT REMARKABLE: 1 0 0 5 4 0 0 5 -- MYOCARDITIS, VENTRICULAR REGION Minimal> 4 0 0 0 0 0 0 0 Total> 4 0 0 0 0 0 0 0 KIDNEYS ................................................ NUMBER EXAMINED: 5 0 0 5 4 0 0 5 NOT REMARKABLE: 2 0 0 3 1 0 0 4 -- CORTICAL TUBULAR BASOPHILIA Minimal> 2 0 0 1 1 0 0 1 Slight> 0 0 0 0 1 0 0 0 Total> 2 0 0 1 2 0 0 1 -- CORTICAL LYMPHOCYTIC INFILTRATION Minimal> 0 0 0 0 1 0 0 0 Total> 0 0 0 0 1 0 0 0 -- CORTICAL INTERSTITIAL FIBROBLAST PROLIFERATION/ FIBROSIS Slight> 0 0 0 0 1 0 0 0 Total> 0 0 0 0 1 0 0 0 -- UROTHELIAL HYPERPLASIA, UNILATERAL Minimal> 0 0 0 0 0 0 0 1 Total> 0 0 0 0 0 0 0 1 -- PELVIC DILATATION Moderate> 0 0 0 0 0 0 0 1 Total> 0 0 0 0 0 0 0 1 -- MINERALISATION, CORTICOMEDULLARY Minimal> 1 0 0 0 0 0 0 0 Total> 1 0 0 0 0 0 0 0 -- MEDULLARY MINERALISATION Total> 0 0 0 0 0 0 0 0 Main study animals GROUP COMPOUND EXPOSURE LEVEL(PPM): 1 CONTROL 0 TABLE 8 (Microscopic pathology 234 ------- -POSF-------30 100 300 SEX: GROUP: ORGAN/TISSUE EXAMINED NUMBER: ** FROM PREVIOUS PAGE ** KIDNEYS ...................................... .......... NUMBER EXAMINED: NOT REMARKABLE: OO OO -- FOCAL CAPSULAR CONGESTION Minimal> Total> -- MEDULLARY TUBULAR BASOPHILIA Total> -- MEDULLARY TUBULAR FIBROSIS Total> LARYNX ....................................... .......... NUMBER EXAMINED: NOT REMARKABLE: -- NECROSIS OF VENTRAL CARTILAGE Present> Total> -- ARYTENOID - EPITHELIAL HYPERPLASIA Minimal> Total> -- ARYTENOID - EPITHELIAL HYPERKERATOSIS PARAKERATOSIS Total> -- ARYTENOID - SUBEPITHELIAL INFLAMMATORY CELL INFILTRATION Minimal> Total> -- VENTROLATERAL EPITHELIAL HYPERPLASIA Total> -- VENTROLATERAL EPITHELIAL SQUAMOUS METAPLASIA Total> -- VENTRAL POUCH - EPITHELIAL HYPERPLASIA Minimal> Total> - continued) Print No: 0029 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D -- -------MALE------- -- -- FEMALE------1- -2- -3- -4- -1- -2- -3- -4- 55 5 5 4 5 55 U) (J1 14 0 0 05 04 0 0 00 0 1 0 00 0 1 0 00 00 0 0 00 00 00 0 0 0 00 0 00 5 55 54 5 55 4 5 4 13 4 40 0 00 00 0 40 40 0 0 05 05 10 0 21 0 02 1 00 21 0 02 0 0 0 00 0 00 0 0 110 0 0 110 0 00 0 00 000000 00 000000 00 00 00 00 00 00 11 11 00 MIN 313/023622 Main study animals GROUP COMPOUND EXPOSURE LEVEL(PPM): 1 CONTROL 0 TABLE 8 (Microscopie pathology 23 -------- POSF---30 100 4 300 SEX: GROUP: ORGAN/TISSUE EXAMINED NUMBER: ** FROM PREVIOUS PAGE ** LARYNX ................................................. .. NUMBER EXAMINED: OO NOT REMARKABLE: o -- VENTRAL POUCH - INFLAMMATORY CELL INFILTRATION Total> -- VENTRAL POUCH - FORIGN BODY IN LUMEN, RELATED TO EPITHELIAL HYPERPLASIA/ INFLAMMATORY CELL INFILTRATION Total> -- PROMINENT DILATED ACINI VENTRAL GLAND Total> LIVER .................................................. .. NUMBER EXAMINED: NOT REMARKABLE: -- CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA Slight> Moderate> Total> -- CENTRILOBULAR HEPATOCYTE HYPERTROPHY Slight> Total> -- CENTRILOBULAR HEPATOCYTE NECROSIS/INFLAMMATORY CELL INFILTRATION/SINUSOIDAL CONGESTION Total> -- PROMINENT CENTRILOBULAR HEPATOCYTE PIGMENT Minimal> Total> -- FOCAL/MULTIFOCAL SINGLE CELL NECROSIS INFLAMMATORY CELL INFILTRATION Minimal> Total> - continued) Print No: 0029 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D --------MALE------- -- -- FEMALE------1- -2- -3- -4- -1- -2- -3- -4- 55 5 5 4 5 55 15 5 5 5 4 5 5 5 454 3440 000000 00 000000 00 000000 00 0 0 05 5 5 5 4 5 5 5 4 2 4 40 000 40 4 0 5 5 0 5 5 000 0 0 0 03 02 05 00 11 00 00 00 00 00 00 000000 00 00 00 00 00 00 0 0 01 01 00 00 00 11 00 0 0 0 0 0 0 MIN 313/023622 Main study animals GROUP COMPOUND EXPOSURE LEVEL(PPM): i CONTROL 0 TABLE 8 (Microscopie pathology 234 -- POSF--- 30 100 300 SEX: GROUP : ORGAN/TISSUE EXAMINED NUMBER : ** FROM PREVIOUS PAGE ** LIVER ................................................... NUMBER EXAMINED: NOT REMARKABLE: -- PARENCHYMAL INFLAMMATORY CELL INFILTRATION Minimal> Total> -- PERIPORTAL LYMPHOCYTIC INFILTRATION Minimal> Slight> Total> -- CENTRILOBULAR INFLAMMATORY CELL INFILTRATION Total> -- EXTRAMEDULLARY HAEMOPOEISIS Minimal> Total> -- PERIPORTAL HEPATOCYTE VACUOLATION Minimal> Total> -- CENTRILOBULAR HEPATOCYTE VACUOLATION Minimal> Slight> Total> -- HEPATOCYTE VACUOLATION, MEDIAN CLEFT Minimal> Total> LUNGS & BRONCHI ........................................ NUMBER EXAMINED: NOT REMARKABLE: -- FOCAL BRONCHOALVEOLAR HYPERPLASIA Total> - continued) Print No: 0029 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D --------MALE------- -- -- FEMALE------1- -2- -3- -4- -1- -2- -3- -4- 55554555 5 5 554 4 0 0 02 0 10 0 10 00 00 10 00 00 00 01 1 0 0 01 00000 00 11 11 00 11 00 00 00 00 00 00 00 31 0 0 00 00400 00 00 00 00 00 )U (J1 554 303 0 55 44 00 00 101 0 0 0 00 5 0 00 000 0 00 00 0 0 0 10 0 10 00 00 00 0 0 0 00 00 1 1 55 33 5 0 00 0 MIN 313/023622 Main study animals GROUP COMPOUND EXPOSURE LEVEL(PPM): 1 CONTROL 0 TABLE 8 (Microscopie pathology 234 -- POSF--- 30 100 300 SEX: GROUP : ORGN/TISSUE EXAMINED NUMBER : ** FROM PREVIOUS PAGE ** LUNGS & BRONCHI ........................................ NUMBER EXAMINED: NOT REMARKABLE: -- FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES Minimal> Slight> Moderate> Total> -- AGGREGATIONS OF ALVEOLAR MACROPHAGES Minimal> Slight> Total> -- ALVEOLITIS Minimal> Total> -- ALVEOLAR HAEMORRHAGE Minimal> Marked> Total> -- PERIVASCULAR INFLAMMATORY CELL INFILTRATION Minimal> Total> -- PROMINENT AGGREGATIONS OF LYMPHOCYTES Minimal> Total> -- VASCULAR CONGESTION Slight> Total> -- FOCAL OSSEOUS DEPOSITION Minimal> Total> - continued) Print No: 0029 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D --------MALE------- -- -- FEMALE------1- -2- -3- -4- -1- -2- -3- -4- 55554555 U) (J1 5 5 4 55 5 3 03 33 0 00 0 3 0 0 12 00 00 0 00 1 0 0 0 0 10 20 00 0 5 0 0 14 20 00 20 00 0 00 0 01 1 101 110 0 0 0 22 11 00 11 00 00 0 00 0 220 110 011 20 2 110 00 0 00 0 00 00 00 00 00 11 00 0 0 10 0 0 10 0 00 0 00 0 0 10 0 0 10 0 00 0 00 00 00 00 00 00 10 10 20 2 11 0 0 0 0 3 3 MI N 313/023622 Main study animals GROUP COMPOUND EXPOSURE LEVEL(PPM): i CONTROL 0 TABLE 8 (Microscopic pathology 234 -- POSF--- 30 100 300 SEX: GROUP: ORGAN/TISSUE EXAMINED NUMBER: ** FROM PREVIOUS PAGE ** LUNGS & BRONCHI ........................................ NUMBER EXAMINED: (OO -- EARLY AUTOLYSIS NOT REMARKABLE: Total> TRACHEA ................................................. NUMBER EXAMINED: NOT REMARKABLE: -- EPITHELIAL HYPERPLASIA Minimal> Total> -- EPITHELIAL INFLAMMATORY CELL INFILTRATION Minimal> Total> -- SUBEPITHELIAL INFLAMMATORY AGGREGATIONS Minimal> Total> -- SUBEPITHELIAL FIBROBLAST PROLIFERATION Minimal> Total> TRACHEAL BIFURC......................................... NUMBER EXAMINED: NOT REMARKABLE: URINARY BLADDER ........................................ NUMBER EXAMINED: NOT REMARKABLE: EPIDIDYMIDES ........................................... NUMBER EXAMINED: NOT REMARKABLE: LN MANDIBULAR .......................................... NUMBER EXAMINED: NOT REMARKABLE: - continued) Print No: 0029 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D -- -------MALE------- -- -- FEMALE------1- -2- -3- -4- -1- -2- -3- -4- 55554555 )U (J1 554 5 55 303 3 30 0 00 00 0 00 5 0 0 5 4 0 05 5 0 0 3 4 0 05 0 0 00 0 2 0 00 0 2 0 00 00 0 0 00 0 1 0 00 0 1 0 00 00 0 0 0 1 0 0 00 0 0 0 10 0 00 0 0 0 10 0 00 0 0 0 10 0 00 5 0 0 5 4 0 05 5 0 0 5 4 0 05 50 054 0 50 054 0 00 00 00 00 00 0 0 00 00 00 00 00 0 0 05 05 00 00 00 00 MIN 313/023622 MIN 313/023622 : 93 : Main study animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 ORGAN/TISSUE EXAMINED MISCELLANEOUS ......... PREPUTIAL GLANDS ...... PROSTATE ............... SKIN ................... STOMACH ................ TAIL ................... THYMUS ................. URETERS ................ UTERUS ................. -- LUMINAL DILATATION ** END OF LIST ** TABLE 8 (Microscopic pathology - continued) Print No: 0029 34 POSF-------- 100 300 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D ---- SEX: ---MALE --- --- --- --FEMALE-- GROUP: -1- -2- -3- -4- -1- -2- -3- -4- NUMBER: 5 5 5 5 4 5 5 5 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 NUMBER EXAMINED: 0 0 0 0 0 0 0 0 NOT REMARKABLE: 0 0 0 0 0 0 0 0 Total> 0 0 0 0 0 0 0 0 Recovery phase animals GROUP COMPOUND EXPOSURE LEVEL(PPM): 1 CONTROL 0 TABLE 8 (Microscopie pathology 234 -- POSF--- 30 100 300 SEX: GROUP : ORGAN/TISSUE EXAMINED NUMBER: ** TOP OF LIST ** HEART ................................................... NUMBER EXAMINED: 4o^ -- MYOCARDITIS, VENTRICULAR REGION NOT REMARKABLE: Total> KIDNEYS ................................................. NUMBER EXAMINED: NOT REMARKABLE: -- CORTICAL TUBULAR BASOPHILIA Minimal> Slight> Total> -- CORTICAL LYMPHOCYTIC INFILTRATION Minimal> Slight> Total> -- CORTICAL INTERSTITIAL FIBROBLAST PROLIFERATION/ FIBROSIS Total> -- UROTHELIAL HYPERPLASIA, UNILATERAL Total> -- PELVIC DILATATION Slight> Total> -- MINERALISATION, CORTICOMEDULLARY Minimal> Total> -- MEDULLARY MINERALISATION Minimal> Total> -- FOCAL CAPSULAR CONGESTION Total> - continued) Print No: 0031 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D -- -------MALE------- -- -- FEMALE------1- -2- -3- -4- -1- -2- -3- -4- 55554555 5 0 0 5 4 0 05 5 0 0 5 4 0 05 0 00 00 0 00 5 0 0 5 4 0 05 0 0 0 2 2 0 04 31 0 0 40 00 0 12 0 0 30 000 01 0 0 0 0 01 0 0 0 0 02 0 0 0 0 0 00 00 0 000 000 000 000 00 00000000 1 1 0 0 0 0 0 0 0 0 00 00 00 00002001 00002001 11 00 00 11 11 00 00 00 00000000 MIN 313/023622 Recovery phase animals GROUP COMPOUND EXPOSURE LEVEL(PPM): 1 CONTROL 0 TABLE 8 (Microscopic pathology 234 -- POSF--- 30 100 300 SEX: GROUP: ORGAN/TISSUE EXAMINED NUMBER: ** FROM PREVIOUS PAGE ** KIDNEYS ................................................. NUMBER EXAMINED: NOT REMARKABLE: -- MEDULLARY TUBULAR BASOPHILIA Minimal> Total> -- MEDULLARY TUBULAR FIBROSIS Minimal> Total> LARYNX .................................................. NUMBER EXAMINED: NOT REMARKABLE: -- NECROSIS OF VENTRAL CARTILAGE Present> Total> -- ARYTENOID - EPITHELIAL HYPERPLASIA Minimal> Slight> Total> -- ARYTENOID - EPITHELIAL HYPERKERATOSIS PARAKERATOSIS Minimal> Total> -- ARYTENOID - SUBEPITHELIAL INFLAMMATORY CELL INFILTRATION Minimal> Total> -- VENTROLATERAL EPITHELIAL HYPERPLASIA Minimal> Total> -- VENTROLATERAL EPITHELIAL SQUAMOUS METAPLASIA Minimal> Total> - continued) Print No: 0031 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D --------MALE------- -- -- FEMALE------1- -2- -3- -4- -1- -2- -3- -4- 55554555 50 054 0 05 0 0 0 2 2 0 04 0 0 0 0 0 0 10 10 00 00 00 0 0 0 0 0 0 10 10 00 00 00 5 5 5 5 4 5 55 5 4 4 1 4 4 42 0 0 0 40 0 03 0 0 0 40 0 03 0 110 0 00 10 1 0 2 2 00 00 0 00 00 00 0 00 20 0 0 00 20 0 0 10 0 10 0 0 0 0 0 0 00 00 01 01 000100 000100 00 00 00 11 00 0 0 00 00 00 00 MIN 313/023622 Recovery phase animals GROUP COMPOUND EXPOSURE LEVEL(PPM): 1 CONTROL 0 TABLE 8 (Microscopie pathology 23 -------- POSF---30 100 4 300 SEX: GROUP: ORGAN/TISSUE EXAMINED NUMBER: ** FROM PREVIOUS PAGE ** LARYNX ................................................. .. NUMBER EXAMINED: NOT REMARKABLE: O Os -- VENTRAL POUCH - EPITHELIAL HYPERPLASIA Minimal> Total> -- VENTRAL POUCH - INFLAMMATORY CELL INFILTRATION Minimal> Total> -- VENTRAL POUCH - FORIGN BODY IN LUMEN, RELATED TO EPITHELIAL HYPERPLASIA/ INFLAMMATORY CELL INFILTRATION Slight> Moderate> Total> -- PROMINENT DILATED ACINI VENTRAL GLAND Present> Total> LIVER .................................................. .. NUMBER EXAMINED: NOT REMARKABLE: -- CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA Slight> Total> -- CENTRILOBULAR HEPATOCYTE HYPERTROPHY Minimal> Slight> Total> -- CENTRILOBULAR HEPATOCYTE NECROSIS/INFLAMMATORY CELL INFILTRATION/SINUSOIDAL CONGESTION Moderate> Total> -- PROMINENT CENTRILOBULAR HEPATOCYTE PIGMENT Minimal> Total> - continued) Print No: 0031 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D -- -------MALE------- -- -- FEMALE------1- -2- -3- -4- -1- -2- -3- -4- 55554555 5 5 55455 5 5 4 414 4 4 2 0 0 0 0 0 0 20 20 00 00 00 0 0 0 0 0 0 20 20 00 00 00 000 000 000 000 000 10 0 1 0 0 110 00 00 00 00 00 0 0 0 0 1 1 1 0 05 5 5 5 4 5 5 5 5 2 54 1 Ul Ul 00 0 0 00 0 0 0 13 0 0 00 4 0 2 0 0 0 00 0 0 3 3 0 0 00 4 0 0 0 1 0 00 0 0 0 0 1 0 00 0 00 00 00 00 00 00 00 22 MIN 313/023622 Recovery phase animals GROUP COMPOUND EXPOSURE LEVEL(PPM): i CONTROL 0 TABLE 8 (Microscopie pathology 234 -- POSF--- 30 100 300 SEX: GROUP : ORGAN/TISSUE EXAMINED NUMBER : ** FROM PREVIOUS PAGE ** LIVER ................................................... NUMBER EXAMINED: O<1 -- FOCAL/MULTIFOCAL SINGLE CELL NECROSIS NOT REMARKABLE: Total> INFLAMMATORY CELL INFILTRATION -- PARENCHYMAL INFLAMMATORY CELL INFILTRATION Minimal> Total> -- PERIPORTAL LYMPHOCYTIC INFILTRATION Minimal> Total> -- CENTRILOBULAR INFLAMMATORY CELL INFILTRATION Minimal> Total> -- EXTRAMEDULLARY HAEMOPOEISIS Minimal> Total> -- PERIPORTAL HEPATOCYTE VACUOLATION Total> -- CENTRILOBULAR HEPATOCYTE VACUOLATION Slight> Total> -- HEPATOCYTE VACUOLATION, MEDIAN CLEFT Slight> Total> LUNGS & BRONCHI ........................................ NUMBER EXAMINED: NOT REMARKABLE: -- FOCAL BRONCHOALVEOLAR HYPERPLASIA Minimal> Total> - continued) Print No: 0031 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D -- -------MALE------- -- -- FEMALE------1- -2- -3- -4- -1- -2- -3- -4- 55554555 1 0 05 5 5 5 4 5 5 25 55 41 0 0 0 0 0 0 00 00 00 00 00 00 00 11 00 00 00 11 00 11 00 00 00 00 00 00 11 00 00 00 00 00 11 11 00 11 0 0 0 0 1 1 0000000 0 00 11 00 00 00 0 0 0 0 0 0 00 00 00 11 00 0 0 0 0 0 0 U) (J1 05 4 5 5 5 2 44 1 00 00 00 11 00 00 00 00 MIN 313/023622 Recovery phase animals GROUP COMPOUND EXPOSURE LEVEL(PPM): 1 CONTROL 0 TABLE 8 (Microscopie pathology 234 -- POSF--- 30 100 300 SEX: GROUP : ORGAN/TISSUE EXAMINED NUMBER: ** FROM PREVIOUS PAGE ** o LUNGS & BRONCHI ........................................ NUMBER EXAMINED: 00 NOT REMARKABLE: -- FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES Minimal> Slight> Total> -- AGGREGATIONS OF ALVEOLAR MACROPHAGES Minimal> Total> -- ALVEOLITIS Minimal> Total> -- ALVEOLAR HAEMORRHAGE Minimal> Slight> Total> -- PERIVASCULAR INFLAMMATORY CELL INFILTRATION Minimal> Total> -- PROMINENT AGGREGATIONS OF LYMPHOCYTES Total> -- VASCULAR CONGESTION Total> -- FOCAL OSSEOUS DEPOSITION Minimal> Total> -- EARLY AUTOLYSIS Total> - continued) Print No: 0031 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D -- -------MALE------- -- -- FEMALE------1- -2- -3- -4- -1- -2- -3- -4- 55554555 U) (J1 05 4 5 5 5 2 44 1 101 101 1 01 2 3 5 000 10 0 0 10 20 2 00 0 0 11 00 2 2 00 00 2 2 11 0 0 11 00 00 00 00 00 000 0 0 0 0 0 0 000 011 0 10 00 0 0 10 1 12 0 0 1 12 0 0 00 00 1 1 0 0 00 0 00 0 0 0 00 0 00 0 11 11 000 0 00 00 00 2 2 0000000 0 MIN 313/023622 Recovery phase animals GROUP COMPOUND EXPOSURE LEVEL(PPM): 1 CONTROL 0 TABLE 8 (Microscopic pathology 234 -- POSF--- 30 100 300 ORGAN/TISSUE EXAMINED SEX: GROUP: NUMBER: TRACHEA ................................................. NUMBER EXAMINED: NOT REMARKABLE: -- EPITHELIAL HYPERPLASIA Total> -- EPITHELIAL INFLAMMATORY CELL INFILTRATION Total> -- SUBEPITHELIAL INFLAMMATORY AGGREGATIONS Slight> Total> -- SUBEPITHELIAL FIBROBLAST PROLIFERATION Total> TRACHEAL BIFURC......................................... NUMBER EXAMINED: NOT REMARKABLE: URINARY BLADDER ........................................ NUMBER EXAMINED: NOT REMARKABLE: EPIDIDYMIDES ........................................... NUMBER EXAMINED: NOT REMARKABLE: LN MANDIBULAR .......................................... NUMBER EXAMINED: NOT REMARKABLE: MISCELLANEOUS .......................................... NUMBER EXAMINED: NOT REMARKABLE: PREPUTIAL GLANDS NUMBER EXAMINED: NOT REMARKABLE: - continued) Print No: 0031 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D --------MALE------- -- -- FEMALE------1- -2- -3- -4- -1- -2- -3- -4- 55554555 5 0 0 5 4 0 05 5 0 0 44 0 05 0 0 000 0 00 0 0 000 0 00 0 0 0 0 0 0 10 10 00 00 00 0 0 000 0 00 5 0 0 5 4 0 05 5 0 0 5 4 0 05 5 0 0 5 4 0 05 5 0 0 5 4 0 05 00 00 00 00 00 0 0 00 00 0 0 000 0 00 0 0 0 00 0 00 0 0 0 00 0 00 0 0 0 00 0 00 0 0 0 00 0 00 0 0 0 00 0 00 MIN 313/023622 MIN 313/023622 : 100 : Recovery phase animals GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i 0CONTROL ORGAN/TISSUE EXAMINED PROSTATE ............... SKIN ................... STOMACH ................ TAIL ................... THYMUS ................. URETERS ................ UTERUS ................. -- LUMINAL DILATATION ** END OF LIST ** TABLE 8 (Microscopic pathology - continued) 23 4 100---POSF--- 30 300 Print No: 0031 Printed: 18-SEP-02 Protocol Number: MIN 313 -- N U M B E R - O F - A N I M A L S - A F F E C T E D ---- SEX: ---MALE --- --- --- -- FEMALE-- GROUP: -1- -2- -3- -4- -1- -2- -3- -4- NUMBER: 5 5 5 5 4 5 5 5 00 00 00 00 00 00 00 00NUMBER EXAMINED: NOT REMARKABLE: 00 00 00 00 00 00 00 00NUMBER EXAMINED: NOT REMARKABLE: 00 00 00 00 00 00 00 00NUMBER EXAMINED: NOT REMARKABLE: 00 00 00 00 00 00 00 00NUMBER EXAMINED: NOT REMARKABLE: 00 00 00 00 00 00 00 00NUMBER EXAMINED: NOT REMARKABLE: 00 00 00 00 00 00 00 00NUMBER EXAMINED: NOT REMARKABLE: 00 00 00 00 00 00 00 00NUMBER EXAMINED: NOT REMARKABLE: 0Total> 0 0 0 0 0 0 0 MIN 313/023622 : 101 : APPENDIX 1 Weekly physical examination - individual findings GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 1M 1 7 14 SKIN ENCRUSTATION(S) HEAD STAINING BROWN HEAD 3 7 14 COAT HAIRLOSS FORELIMBS 41 8 18 COAT HAIRLOSS HEAD 43 8 18 EYES PROMINENT RIGHT 45 8 18 SKIN ENCRUSTATION (S) HEAD WEEKS 1-18 2-3 13-14 3-14 13-18 18 13-15 Print No: 0017 Printed : 24-JUN-02 Xybion protocol number : MIN 313 MIN 313/023622 : 102 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 2M 87 14 SKIN ENCRUSTATION (S) TAIL STAINING BROWN DORSAL BODY SURFACE 97 14 COAT HAIRLOSS DORSAL BODY SURFACE 10 7 14 COAT HAIRLOSS HEAD 46 8 18 COAT HAIRLOSS HEAD SKIN ENCRUSTATION (S) HEAD 47 8 18 COAT HAIRLOSS DORSAL BODY SURFACE STAINING BROWN HEAD WEEKS 1-18 7-8 6-10 2-3 13-14 4-5, 8-18 8-9 2-4 10-18 Print No: 0017 Printed : 24-JUN-02 Xybion protocol number : MIN 313 MIN 313/023622 : 103 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 2M 48 8 18 SKIN ENCRUSTATION (S) NOSE DORSAL BODY SURFACE 49 8 18 STAINING BROWN HEAD 50 8 18 COAT HAIRLOSS DORSAL BODY SURFACE SKIN ENCRUSTATION (S) DORSAL BODY SURFACE STAINING BROWN HEAD WEEKS 1-18 15-17 17-18 18 9-18 8 12-18 Print No: 0017 Printed : 24-JUN-02 Xybion protocol number : MIN 313 MIN 313/023622 : 104 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 3M 12 7 14 STAINING RED PENIS 13 7 14 COAT HAIRLOSS DORSAL BODY SURFACE WEEKS 1-18 4 13-14 Print No: 0017 Printed : 24-JUN-02 Xybion protocol number : MIN 313 MIN 313/023622 : 105 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ------- POSF------30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 4M 16 7 14 STAINING BROWN HEAD DORSAL BODY SURFACE 17 7 14 STAINING BROWN HEAD 19 7 14 COAT HAIRLOSS HEAD DORSAL BODY SURFACE SKIN ENCRUSTATION (S) HEAD STAINING BROWN HEAD 20 7 14 STAINING BROWN HEAD 57 8 18 COAT HAIRLOSS HEAD WEEKS 1-18 10-14 5-14 14 4 2-3 4 6-14 14 4-18 Print No: 0017 Printed: 24-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 106 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 4M 58 8 18 COAT HAIRLOSS HEAD DORSAL BODY SURFACE STAINING BROWN DORSAL BODY SURFACE 59 8 18 COAT HAIRLOSS HEAD 60 8 18 COAT HAIRLOSS FORELIMBS WEEKS 1-18 7-9, 17-18 2-18 6-18 5-18 5-18 Print No: 0017 Printed : 24-JUN-02 Xybion protocol number : MIN 313 MIN 313/023622 : 107 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 1F 21 7 14 STAINING BROWN HEAD 22 7 14 STAINING BROWN VENTRAL BODY SURFACE 23 F 13 COAT HAIRLOSS VENTRAL BODY SURFACE STAINING BROWN HEAD 24 7 14 STAINING BROWN HEAD 61 8 18 COAT HAIRLOSS DORSAL BODY SURFACE 62 8 18 COAT HAIRLOSS HEAD DORSAL BODY SURFACE WEEKS 1-18 8 12-14 12-13 12-13 3-8 16-18 6-11 16-18 Print No: 0017 Printed : 24-JUN-02 Xybion protocol number : MIN 313 MIN 313/023622 : 108 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ------- POSF------30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 1F 63 H 3 BUILD (DISPLACEMENT) LEFT HINDLIMB RIGHT HINDLIMB BODY TEMPERATURE REDUCED COAT UNGROOMED EXCRETA FAECES LOOSE MUSCLE REACTION ABNORMAL GAIT SWAYING POSTURE TILTED HEAD LEANS TO THE RIGHT RIGHTING REFLEXES POOR STAINING RED NOSE 64 8 18 STAINING BROWN HEAD 65 8 18 COAT HAIRLOSS FORELIMBS WEEKS 1-18 3 3 3 3 3 3 3 3 3 3-13, 17-18 3-18 Print No: 0017 Printed: 24-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 109 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 2F 27 7 14 STAINING BROWN HEAD DORSAL BODY SURFACE 66 8 18 STAINING BROWN VENTRAL BODY SURFACE DORSAL BODY SURFACE 67 8 18 COAT HAIRLOSS DORSAL BODY SURFACE STAINING BROWN HEAD 68 8 18 COAT HAIRLOSS FORELIMBS HEAD STAINING BROWN HEAD 69 8 18 COAT HAIRLOSS HEAD SKIN ENCRUSTATION (S) HEAD WEEKS 1-18 3- 6 11- 14 12- 17 18 4- 10 12-18 15-18 10-18 12-15 8-18 8, 11-15, 17 Print No: 0017 Printed : 24-JUN-02 Xybion protocol number : MIN 313 MIN 313/023622 : 110 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 2F 70 8 18 STAINING BROWN HEAD WEEKS 1-18 5-6 Print No: 0017 Printed : 24-JUN-02 Xybion protocol number : MIN 313 : III : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ------- POSF------30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 3F 31 7 14 STAINING BROWN HEAD 33 7 14 COAT HAIRLOSS HEAD STAINING BROWN HEAD 34 7 14 STAINING BROWN HEAD DEATH CODE TERMINAL KILL 35 7 14 STAINING BROWN HEAD 71 8 18 STAINING BROWN HEAD 72 8 18 STAINING BROWN HEAD WEEKS 1-18 5-14 7-14 5-14 5-14 14 12-14 18 12-18 Print No: 0017 Printed: 24-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : Zi APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 3F 73 8 18 STAINING BROWN HEAD 75 8 18 COAT HAIRLOSS DORSAL BODY SURFACE WEEKS 1-18 5-18 8-18 Print No: 0017 Printed : 24-JUN-02 Xybion protocol number : MIN 313 MIN 313/023622 MIN 313/023622 : 113 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ------- POSF------30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 4F 36 7 14 COAT HAIRLOSS RIGHT FORELIMB STAINING BROWN HEAD 37 7 14 BUILD (DEFORMITY) PROMINENT AREA TAIL STAINING BROWN VENTRAL BODY SURFACE DORSAL BODY SURFACE 38 7 14 COAT UNGROOMED HAIRLOSS LEFT HINDLIMB STAINING BROWN VENTRAL BODY SURFACE DORSAL BODY SURFACE 39 7 14 STAINING BROWN HEAD WEEKS 1-18 11-14 5-14 9- 14 6-14 5-14 8-14 10- 14 4-14 4-14 6-14 Print No: 0017 Printed: 24-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 114 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 4F 40 7 14 STAINING BROWN HEAD VENTRAL BODY SURFACE DORSAL BODY SURFACE 77 8 18 STAINING BROWN VENTRAL BODY SURFACE DORSAL BODY SURFACE 78 8 18 STAINING BROWN HEAD VENTRAL BODY SURFACE 79 8 18 STAINING BROWN HEAD 80 8 18 STAINING BROWN HEAD WEEKS 1-18 6-14 5-14 5-14 10-18 10-18 6-18 6-18 5-18 5-15 Print No: 0017 Printed : 24-JUN-02 Xybion protocol number : MIN 313 MIN 313/023622 : 115 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 1M 81 7 4 SKIN ENCRUSTATION (S) HEAD WEEKS 1-4 2-3 Print No: 0008 Printed : 24-JUN-02 Xybion protocol number MIN 313A : 911 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 1F 91 7 93 7 94 7 95 7 4 STAINING BROWN HEAD 4 STAINING BROWN UPPER DORSAL THORAX 4 DEATH CODE TERMINAL KILL 4 STAINING BROWN UPPER DORSAL THORAX WEEKS 1-4 4 3-4 4 4 Print No: 0008 Printed : 24-JUN-02 Xybion protocol number MIN 313A MIN 313/023622 MIN 313/023622 : 117 : APPENDIX 1 (Weekly physical examination - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: 4F 96 7 98 7 100 7 4 STAINING BROWN UPPER DORSAL THORAX 4 STAINING BROWN HEAD 4 STAINING BROWN HEAD WEEKS 1-4 4 4 4 Print No: 0008 Printed : 24-JUN-02 Xybion protocol number MIN 313A APPENDIX 2 Daily post - dose observation MIN 313/023622 Group : 1 Compound : Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 MaGinrosutpudy animals Sign Animal Week No. (Number of days in week signs observed) 1 2 3 4 5 6 7 8 9 10 11 12 13 14* 1M Red/brown staining around eyes (Control) 21 34 21 3 5 1 22 2 1 41 211 1 2 1 1 1 111 3 2 1 Wet fur 2341 5 3242 2 55555 43334 55555 55555 3344 3 44555 33334 43333 3434 3 1 11 2 2 3211 1 1 Brown staining on head 1 2 34 5 1 1 1 11 1 111 1 211 2 1 31 1 1 1 2 Brown staining muzzle 4 1 Brown staining body 1 4 2M Red/brown staining around eyes (Low dose) 6 78 190 3 431 1 11 1 21 1 11 2 411 1 2 2 1 11 1 2 1 11 1 Wet fur 167980 434 33 444 44 33333 444 44 445 45 33333 55555 444 44 445 44 34333 1 2 1 Brown staining body 6 3 Brown staining on head 6 78 9 11 A*nAinmimalsalesxspeonstefdorfonrec5rdoapyssyaovweerefkirfsotr31d3aywseoekfsW1e0ek 14 : 118 : 2 41 11 1111 1 1 1 APPENDIX 2 (Daily post - dose observation - continued) MIN 313/023622 Group : 1 Compound : Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 Main study animals Group Sign Animal Week No. (Number of days in week signs observed) 1 2 3 4 5 6 7 8 9 10 11 12 13 14* (Inte3r.Mdose) Red/brown staining around eyes 1112 1 3 11 1 1134 1 11 12 1 1 1 1 15 1 1 1 112 Wet fur 11 12 34 4 4 33 4 4 55 34 55 4 4 4 4 33 2 1 1 1134 15 334 4 44 33 3 4 44 4 44 33 3 55 5 4 45 4 4 5 4 3 3 1 31 25 1 11 Brown staining on head 1112 1 1134 15 1 11 11 1 1 4M Red/brown staining around eyes (High dose) 16 17 1 3 32 1 5 4 2 2 2 2 3 1 21 1189 4 1 2 32 2 2 1 5 3 1 4 2 2 2 1 20 1 1 Wet fur 16 4 5 3 4 5 3 4 5 5 4 5 4 4 1 1178 33 55 33 4 4 55 33 4 4 4 4 55 34 3 1 2 1 2 2109 35 55 33 4 4 55 4 3 4 4 45 55 35 51 4 1 31 1 Brown staining on head 16 17 1 2 1 21 3 21 18 19 1 1111 20 1 11 2 5 2 1 1 12 111 2 Brown staining on muzzle 16 1 A*nAinmimalsalesxspeonBstrefodowrfnonresct5ardionapiysnsygaoovwneebreofkdiryfsotr31d3aywseoekfsW1e9ek 14. 11 : 119 : APPENDIX 2 (Daily post - dose observation - continued) MIN 313/023622 Group : 1 Compound : Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 Main study animals Group Sign Animal Week No. (Number of days in week signs observed) 1 2 3 4 5 6 7 8 9 10 11 12 13 14* 1F Red/brown staining around eyes (Control) 2212 1 22 3 12 11 2234 1 1 2 25 1 Wet fur 21 22 4 4 55 35 55 55 55 55 45 55 55 45 55 55 2 2 2234 25 4 3 3 55 5 334 55 5 55 5 2 22 4 44 344 445 4 44 4 1 3 55 5 55 5 1a 11 Brown staining on head 2212 31 32 1 11 11 2 3 21 2 3 42 4 3 1 2234 132 1 11 21 24 3 3 42 3 3 4 3 11 25 1 2 1 2 1 1 4 2F Red/brown staining around eyes (Low dose) 26 27 2289 30 1 2 2 1 3 2 1 3 51 1 2 11 1 2 3 1 2 12 11 2 11 Wet fur 26 3 4 3 4 5 3 5 4 5 3 5 5 4 2 2278 4 5 4 4 33 4 4 55 34 55 55 55 45 55 45 4 4 2 2 2390 33 4 5 33 4 4 55 4 4 55 4 5 55 35 55 45 35 2 2 Brown staining on head 26 27 11 11 1 21 31 1 28 1 29 2 2 1 1 31 1 1 12 1 2 1 31 2 1 30 1 1 4 2 1 A* nAinmimalsalesxspeonstefdorfonrec5rdoapyssy aovweerefkirfsotr3 1d3aywseoekfsWeek 14. aAnimal No. 23 died at bleed : 120 : APPENDIX 2 (Daily post - dose observation - continued) MIN 313/023622 Group : 1 Compound : Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 Main study animals Group Sign Animal Week No. (Number of days in week signs observed) 1 2 3 4 5 6 7 8 9 10 11 12 13 14* (Inter3.Fdose) Red/brown staining around eyes 3312 11 11 11 1 3334 2 4 1 1 4 2 4 3 3 4 2 5 3 2 2 1 2 1 1 4 2 1 1 35 1 11 42211 1 Wet fur 3312 55 45 33 4 4 55 33 55 4 4 55 35 35 55 4 5 2 1 3334 35 35 5 55 5 344 4 44 55 5 4 44 55 5 4 44 55 5 55 5 455 55 5 55 5 2 22 Brown staining on head 3312 1 3 1 11 2 1 1 22 1 3334 11 2 1 22 3 1 21 1 1 3 25 2 1 2 3 21 35 11 222 1 4F Red/brown staining around eyes (High dose) 36 37 2 11 1 111 11 14 3389 1 2 12 12 12 11 2 40 3 2 1 23 Wet fur 36 4 5 3 4 4 3 5 4 5 4 4 5 3 2 3378 55 55 34 55 55 55 45 55 55 4 5 4 4 45 45 2 2 3490 55 55 33 4 4 45 4 3 55 55 55 55 4 4 55 32 2 2 Brown staining on head 36 37 1 38 39 1 40 1 11 1 2 3 3 1 1 21 1 11 1 112 11 Brown staining body 37 A*nAimniamlsalesxspeonstefdorfonrec5rdoapysys aovweerefkirfsotr31d3aywseoekf3sW8 eek 14. 2 555555552 : 121 : APPENDIX 2 (Daily post - dose observation - continued) MIN 313/023622 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol 2 30 -- P1O30S0F-- 4 300 RGercoouvpery phase animalsSign AnNiom.al (Co1nMtrol) Red/brown staining around eyes 4444412345 511 32 2 (335Num431ber 225o f 32 4 da6ys 23 iW7n111 weeek2238ek s922i11gns1211o0bse1111rved13312) 113 14* Wet fur 4444413245 33333 55555 34355 55555 55555 33343 44444 33334 43443 33335 1 3 32 2111 Brown staining on head 4444413245 1 3 2 21 21111 11 1 1 1 11 (Low2Mdose) Red/brown staining around eyes 4444567890 3 21 1 11 1 221 21 31 41 3 2311 2 33 1111 1 2 2 1 31 21 Wet fur 4444567890 33345 44444 33335 44444 44555 33334 55555 44445 44455 33344 2411 41 1 311 Brown staining on head A* nAinmimalsalesxspeonstefdorfonrec5rdoapyssy aovweerefkirfsotr3 1d3aywseoekf44445sW67890 eek 2 14. 3 1 1 2 1 11111 1 211 1 2 1 21 1 3 : 122 : APPENDIX 2 (Daily post - dose observation - continued) MIN 313/023622 Group : 1 Compound : Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 Recovery phase animals Group Sign Animal Week No. (Number of days in week signs observed) 1 2 3 4 5 6 7 8 9 10 11 12 13 14* 3M Red/brown staining around eyes (Inter. dose) 5512 12 1 1111 13 2 1 1 5534 1 1 11 2 55 1 1 Wet fur 555132 4 44 4 44 335 4 44 544 333 555 4 44 4 45 335 3 1 1 21 54 55 45 4 4 33 4 4 55 33 55 4 4 55 34 2 2 2 1 4 Brown staining on head 5512 1 1 2 11 5534 1 1 11 55 1 13 2 2 4M Red/brown staining around eyes (High dose) 5567 2 58 2 2 11 1 1 59 60 1 1 1 3 2 2 3 3 2 2 2 1 5 4 1 Wet fur 56 4 5 3 4 5 3 4 4 5 3 1 2 5578 59 4 44 55 5 344 4 44 4 4 5 34 3 4 54 4 44 55 5 33 3 344 2 5 1 2 5 60 4 5 3 4 4 3 4 4 5 3 1 Brown staining on head 5567 1 58 1 2 111 59 1 2 1 60 1 11 1 2 1 Animals exposed for 5 days a week for 13 weeks * Animals sent for necropsy over first 3 days of Week 14. : 123 : APPENDIX 2 (Daily post - dose observation - continued) MIN 313/023622 GCoromuppound :: Con1trol Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 RecGorvoeurpy phase animals Sign AnNiom.al (Co1nFtrol) Red/brown staining around eyes 66661234 65 421111 21 11 (31Num411ber5of da621ys iW7n1 weee34k8ek s92i1gns1o0bse121rved112) 13 14* 1 11 1 4 Wet fur 6612 666345a 34 235 55555 43341 55 55 55 55 43 32 55 55 45 45 55 55 45 44 45 45 55 55 55 55 Brown staining on head 6666631245a 1 21 1 32 32 42 1 23 43 21 51 33 4 42 22 2 32 45 34 35 32 Loss of use of hind limbs 63a 1 Unsteady gait 63a 1 Brown staining muzzle 61 1 (Low2Fdose) Red/brown staining around eyes 6666767890 21 31 1 22 221 1 2 1 1 1 1 42 231 1 1 221 3 Wet fur 6666767890 44445 45555 33333 44455 55555 43355 55555 44555 55555 44455 45555 55555 45555 Brown staining on head 6666767890 1 2211 1 1 22351 411 2211 21111 2 23111 21 3 2321 2 21 3 Brown staining body 70 Animals exposed for 5 days a week for 13 weeks a* AAnniimmaalls6s3ekntillfeodr nfoercrhoupmsyanoeverreafsirosnts3indaWyseeokf W3. eek 14. : 124 : 1 APPENDIX 2 (Daily post - dose observation - continued) MIN 313/023622 Group : 1 Compound : Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 Recovery phase animals Group Sign Animal Week No. (Number of days in week signs observed) 1 2 3 4 5 6 7 8 9 10 11 12 13 14* 3F Red/brown staining around eyes 71 2 1 (Inter. dose) 72 1 2 1 73 1 1 2 74 1 75 1 Wet fur 7712 45 55 33 4 4 55 4 4 55 55 55 55 55 55 45 7734 75 4 44 455 4 3 3 4 44 55 5 4 44 55 5 445 55 5 35 5 55 5 55 5 4 44 Brown staining on head 71 72 73 74 75 11 2 11 122 11 11 4 1 112 1 2 1 1122 1 4F Red/brown staining around eyes (High dose) 76 77 4 222 1 21 1 31 7789 12 43 12 1 1 14 4 3 4 80 1 1 Wet fur 76 5 5 3 4 5 4 4 4 5 4 5 5 5 77 78 5 5 5 5 3 3 4 5 5 5 45 5 5 4 5 5 5 4 5 4 5 5 5 3 5 7890 44 55 33 45 55 34 45 55 55 45 55 55 44 Brown staining on head 76 77 11 78 79 2 11 80 11 22 3 11 1 15 12 42 2 1114532 A*nAimniamlsalesxsBpeornostewfdonrfosntreac5inrdoinapgysysboaodvwyeerefkirfsotr31d3aywseoekf77sW68 eek 14. 33 : 125 : APPENDIX 2 (Daily post - dose observation - continued) MIN 313/023622 Group : 1 Compound : Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 Satellite study animals Group Sign 1M Red/brown staining around eyes (Control) Animal Week No. (Number of days in week signs observed) 12 3 4 81 4 1 2 82 83 1 4 3 1 2 2 84 1 2 85 3 3 4 1 Wet fur 81 4 5 4 5 82 8834 334 55 5 35 5 55 5 85 5 5 5 5 Brown staining on head 81 1 82 83 1 84 85 1 21 11 34 21 1F Red/brown staining around eyes 91 2 2 3 1 (Control) 92 1 2 93 3 1 94 1 2 95 1 Wet fur 9912 33 55 4 3 55 9934 95 2 22 55 5 4 4 3 55 5 Brown staining on head Animals exposed for 5 days a week for 4 weeks 91 92 93 94 95 1 31 1 45 2 22 : 126 : APPENDIX 2 (Daily post - dose observation - continued) MIN 313/023622 Group : 1 Compound : Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 Satellite study animals Group Sign 4M Red/brown staining around eyes (High dose) Animal Week No. (Number of days in week signs observed) 12 3 4 86 4 1 87 88 1 1 1 1 89 90 211 1 Wet fur 86 4 5 3 4 8878 89 4 4 5 55 5 33 3 4 44 90 4 5 3 4 Brown staining on head 87 1 89 90 13 4F Red/brown staining around eyes 97 (High 98 dose) 99 100 2 1 1 1 Wet fur 9967 98 4 4 5 55 5 34 3 4 44 19090 33 55 33 4 4 Brown staining on head 96 98 11 99 100 Animals exposed for 5 days a week for 4 weeks 1 11 : 127 : MIN 313/023622 : 128 : APPENDIX 3 Bodyweights - individual values (g) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 GROUP WEEK ANIMAL -1 WEEK 0 WEEK 1 WEEK 2 WEEK 3 1M i 248 292 328 356 386 2 224 252 276 307 338 3 227 263 284 311 337 4 226 248 266 291 314 5 232 253 275 296 313 41 229 252 281 296 312 42 247 275 296 324 355 43 229 246 273 302 323 44 236 257 279 298 316 45 228 268 300 316 337 2M 6 241 278 304 337 365 7 224 239 254 272 287 8 232 279 328 342 372 9 237 276 292 319 344 10 235 257 265 293 321 46 244 282 311 336 365 47 225 240 253 271 283 48 245 282 308 323 343 49 221 251 275 289 307 50 246 284 305 321 343 3M 11 235 264 290 308 333 12 238 272 295 318 332 13 237 270 293 302 341 14 239 263 269 288 317 15 234 255 277 291 310 51 245 274 291 317 339 52 236 271 294 313 329 53 232 265 289 320 342 54 245 275 297 315 332 55 214 227 242 255 266 WEEK 4 410 346 359 339 337 336 382 342 344 363 393 302 392 364 336 391 299 361 323 356 354 360 369 331 336 364 350 363 352 282 WEEK 5 428 363 378 355 365 352 408 365 368 379 409 319 416 374 352 409 309 375 336 371 376 380 395 349 353 380 360 374 363 294 Print No: 0018 Printed: 24-JUN-02 WEEK 6 Xybion protocol number: MIN 313 WEEK 7 WEEK 8 WEEK 9 447 460 474 492 376 396 404 412 399 408 423 435 371 390 402 422 378 398 402 417 374 387 402 412 420 434 451 461 382 404 416 436 390 409 425 432 392 404 409 416 437 452 469 490 332 352 366 380 412 430 451 466 393 408 416 426 368 391 404 419 427 442 459 472 324 335 344 351 398 422 434 442 354 366 373 376 380 392 408 409 390 405 416 421 396 413 424 441 412 430 451 459 366 379 392 400 370 380 399 415 398 406 421 435 373 394 407 410 397 401 410 413 374 390 402 418 312 325 336 347 MIN 313/023622 : 129 : APPENDIX 3 (Bodyweights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 GROUP WEEK ANIMAL -1 WEEK 0 WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 4M 16 234 262 289 309 330 351 364 17 220 241 254 267 285 298 301 18 227 258 274 303 324 343 356 19 238 267 283 304 329 351 357 20 234 260 276 295 310 330 339 56 269 261 266 292 319 338 353 57 227 263 288 321 346 368 382 58 240 261 277 291 311 328 339 59 217 243 255 280 293 306 314 60 234 261 275 294 314 334 358 1F 21 171 184 190 205 217 230 230 22 170 185 199 206 208 225 239 23 173 188 198 208 229 238 239 24 177 193 202 207 225 234 246 25 177 191 206 217 224 229 241 61 195 207 217 237 246 262 268 62 174 188 201 213 213 216 231 63 189 196 214 231 A 64 186 194 196 210 211 223 216 65 172 185 197 197 211 227 232 2F 26 177 195 206 213 215 229 240 27 178 176 189 199 202 195 207 28 180 190 198 202 208 206 219 29 165 172 178 189 202 208 209 30 164 170 184 187 194 196 206 66 188 208 227 238 252 262 271 67 163 191 210 221 237 252 263 68 177 184 204 208 217 210 227 69 183 199 215 220 226 236 249 70 174 183 203 208 233 246 250 Animal N o . 63 sent for necropsy for humane reasons therefore no further bodyweights 375 316 373 373 347 372 395 348 320 381 250 237 251 240 252 276 241 227 243 247 206 232 225 216 274 269 233 256 250 Print No: 0018 Printed: 24-JUN-02 Xybion protocol number: MIN 313 WEEK 7 WEEK 8 WEEK 9 379 387 384 322 326 329 378 386 387 387 389 402 348 359 361 386 399 404 409 419 423 362 388 377 331 339 345 393 402 410 259 263 258 238 245 255 254 257 259 257 261 265 260 258 268 282 287 294 251 246 263 239 253 243 252 256 266 243 256 257 221 213 227 239 240 247 230 231 225 223 225 233 278 283 288 280 293 287 232 234 241 259 268 273 261 269 272 GROUP : COMPOUND EXPOSURE LEVEL(PPM): 1 CONTROL 0 23 -------- POSF 30 100 -1GROUP WEEK ANIMAL 0WEEK 1WEEK 2WEEK 3F 31 171 182 193 197 32 186 201 209 215 33 168 172 200 191 34 194 209 227 240 35 169 189 187 207 71 169 187 203 201 72 187 187 194 196 73 181 201 211 216 74 182 185 199 205 75 166 176 184 195 4P 36 185 193 213 208 37 176 180 202 211 38 178 198 211 209 39 167 178 192 196 40 184 203 190 226 76 163 173 186 184 77 174 181 195 190 78 190 206 211 211 79 188 207 228 238 80 182 185 202 191 APPENDIX 3 (Bodyweights - continued) 4 300 WEEK 3 200 226 201 251 219 217 200 221 200 202 207 218 225 204 234 188 189 215 244 202 WEEK 4 219 243 202 252 227 226 208 236 214 210 219 219 231 205 244 192 195 215 249 204 WEEK 5 221 249 208 267 237 228 216 231 217 208 228 228 239 215 252 200 192 224 263 212 Print No: 0018 Printed: 24-JUN-02 WEEK 6 Xybion protocol number: MIN 313 WEEK 7 WEEK 8 WEEK 9 227 227 237 237 249 262 271 275 214 222 214 217 280 278 280 290 243 250 258 256 238 240 246 245 223 229 232 238 239 250 252 255 223 216 225 236 221 224 232 234 234 230 238 243 240 244 240 246 239 244 244 256 218 223 221 225 256 259 263 265 199 205 211 213 205 208 216 219 226 231 229 234 268 271 271 277 224 238 235 235 MIN 313/023622 MIN 313/023622 : 131 : APPENDIX 3 (Bodyweights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 GROUP ANIMAL WEEK 10 WEEK 11 1M 1 2 3 4 5 41 42 43 44 45 2M 6 7 8 9 10 46 47 48 49 50 3M 11 12 13 14 15 51 52 53 54 55 500 426 456 427 433 421 465 444 447 418 490 388 475 431 423 483 359 450 381 425 431 451 448 403 432 446 418 406 427 362 510 433 464 444 440 433 476 454 461 424 505 401 470 438 432 486 370 463 394 425 435 458 453 412 450 455 426 434 440 366 234 -------- POSF-------30 100 300 WEEK 12 WEEK 13 WEEK 14 516 506 436 429 470 462 449 437 453 455 449 464 473 492 488 500 461 466 487 471 477 489 430 439 446 512 511 409 410 474 481 450 441 435 426 492 495 504 372 378 394 470 468 476 395 403 417 434 442 464 442 436 469 464 455 454 415 402 461 458 468 460 475 440 434 446 442 454 478 451 467 481 375 380 397 WEEK 15 485 516 500 502 455 509 409 488 431 471 501 459 492 493 409 WEEK 16 499 529 515 518 466 521 422 490 441 478 505 468 501 499 407 Print No: 0018 Printed: 24-JUN-02 Xybion protocol number: MIN 313 WEEK 17 506 542 531 533 472 533 435 500 444 491 514 487 509 504 413 MIN 313/023622 : 132 : APPENDIX 3 (Bodyweights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 GROUP ANIMAL WEEK 10 WEEK 11 4M 16 17 18 19 20 56 57 58 59 60 1F 21 22 23 24 25 61 62 64 65 2F 26 27 28 29 30 66 67 68 69 70 3F 31 32 33 34 389 336 395 408 372 413 433 378 358 422 271 254 266 274 272 297 267 260 268 262 234 251 232 239 286 301 242 273 266 238 265 224 300 390 341 401 416 375 416 439 384 358 429 278 255 268 281 279 308 275 269 279 264 233 251 243 247 289 307 246 276 278 238 275 224 287 234 -- POSF--- 30 100 300 WEEK 12 WEEK 13 WEEK 14 394 378 349 337 397 392 422 416 379 357 421 429 444 442 444 461 393 395 406 363 366 386 429 431 431 284 270 261 258 270 282 270 274 274 307 301 313 269 275 287 269 265 277 281 274 288 269 261 230 226 245 243 239 232 245 243 294 293 300 310 301 317 240 234 278 282 287 297 283 281 282 244 233 284 271 221 216 300 300 WEEK 15 461 478 415 399 433 327 293 288 303 312 328 265 295 303 WEEK 16 466 501 426 424 452 326 294 289 312 320 330 274 303 303 Print No: 0018 Printed : 24-JUN-02 Xybion protocol number : MIN 313 WEEK 17 478 515 436 430 466 328 305 277 311 324 330 275 310 299 MIN 313/023622 : 133 : APPENDIX 3 (Bodyweights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 GROUP ANIMAL WEEK 10 WEEK 11 3F 35 71 72 73 74 75 4F 36 37 38 39 40 76 77 78 79 80 256 249 243 255 239 240 244 256 248 227 269 215 222 237 279 241 264 255 247 258 236 240 243 258 257 228 269 217 226 238 280 241 234 -- POSF--- 30 100 300 WEEK 12 WEEK 13 WEEK 14 269 262 254 252 258 246 247 255 264 262 273 242 244 249 243 236 250 248 242 253 240 254 242 224 217 275 259 221 216 223 227 229 241 242 230 255 280 279 291 248 250 257 WEEK 15 268 262 281 249 258 229 251 267 302 268 WEEK 16 268 262 281 259 257 237 258 268 303 273 Print No: 0018 Printed : 24-JUN-02 Xybion protocol number : MIN 313 WEEK 17 274 266 288 259 256 242 262 278 318 272 MIN 313/023622 : 134 : APPENDIX 3 (Bodyweights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 GROUP ANIMAL WEEK -1 WEEK 0 1M 81 82 83 84 85 4M 86 87 88 89 90 1F 91 92 93 94 95 4F 96 97 98 99 100 245 277 244 263 224 242 235 271 237 264 232 270 232 272 235 262 249 277 238 278 172 187 188 194 182 194 174 181 186 197 183 190 182 192 177 190 169 180 167 183 234 -- POSF--- 30 100 300 WEEK 1 WEEK 2 WEEK 3 301 330 358 285 314 341 258 276 290 310 338 366 294 324 351 301 319 339 293 321 342 273 290 305 295 321 343 296 316 331 202 204 216 200 204 210 216 226 245 194 195 208 208 217 236 196 193 200 195 194 202 192 193 200 192 196 200 191 203 217 Print No: 0009 Printed: 24-JUN-02 Xybion protocol number: MIN 313A MIN 313/023622 : 135 : APPENDIX 4 Food consumption - individual values (g/rat) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i 0CONTROL 23 4 100-- POSF--- 30 300 GROUP CAGE -1WEEK 1WEEK 2WEEK WEEK 3 WEEK 4 WEEK 5 6WEEK 1M i 181 180 196 205 213 213 215 9 183 163 176 186 197 198 194 2 202 2012M 192 169 184 197 204 10 195 173 184 190 196 194 196 3M 3 192 175 185 191 198 199 208 11 200190 168 172 192 197 194 124M 4 186 157 173 179 189 181 190 186 150 171 179 188 185 189 1F 5 136 132 136 143 148 149 148 13 137 133 142 145 151 151 153 62F 131 126 126 132 136 138 138 14 150 147 149 157 158 157 156 3F 7 138 134 153 147 151 153 153 15 135 130 133 136 138 137 136 8 122 1214F 144 137 137 140 141 144 144 16 140 128 125 126 127 WEEK 7 214 192 208 198 209 198 180 191 147 151 137 154 151 136 143 125 Print No: 0019 Printed: 24-JUN-02 Xybion protocol number: MIN 313 8WEEK WEEK 9 10WEEK 212216 216 195 193 190 208 207 207 196 193 198 220019 220003 220040 189 180 180 193 187 193 147 146 147 147 148 148 136 139 134 158 151 148 150 148 147 139 136 131 122140 143 140 126 125 MIN 313/023622 : 136 : APPENDIX 4 (Food consumption - continued) OU) 1111111 N> GROUP : COMPOUND : EXPOSURE LEVEL(PPM): GROUP CAGE 11WEEK 1M i 9 2M 102 3M 113 4M 124 1F 5 13 62F 14 3F 7 15 84F 16 218 195 205 198 220022 175 189 149 146 135 150 145 135 112326 i 0CONTROL 12WEEK 220105 203 196 204 199 177 185 145 146 136 147 150 134 136 124 3 100-POSF- 4 300 WEEK 13 WEEK 14 WEEK 15 190 199 198 197 188 199 197 197 181 199 205 205 153 186 190 196 132 147 152 158 121 139 156 160 127 132 138 142 114 118 135 141 WEEK 16 201 206 206 199 190 136 140 137 WEEK 17 203 205 205 200 147 151 138 140 Print No: 0019 Printed: 24-JUN-02 Xybion protocol number: MIN 313 MIN 313/023622 : 137 : APPENDIX 4 (Food consumption - continued) GROUP COMPOUND EXPOSURE LEVEL (PPM) : CONTROL 0 GROUP CAGE WEEK -1 WEEK 1 1M 17 186 169 4M 18 196 161 1F 19 136 138 4F 20 137 122 34 -POSF30 100 300 WEEK 2 WEEK 3 185 197 177 188 145 149 131 136 Print No: 0010 Printed: 24-JUN-02 Xybion protocol number: MIN 313A APPENDIX 5 Haematology - individual values MIN 313/023622 : 138 : Day 91 GCExoropmuoppsuourendlevel (ppm) : 1 Con0trol 2 30 --P1O30S0F------ 4 300 G/rsoeuxp nAunmimbearl LH/cLt gH/dbL x1R0B1C2/L R%etic MCH pg MgC/dHLC MfCLV xW10B9C/L x1N09/L 1M 21 34 5 CC000TT...DD444413177 CC111TT555...DD354 CC7TT88...DD934490 CC233TT...DD110374 CC111TT988...DD335 CC333565TT...DD162 CC555222TT...DD155 CC1TT996...DD889762 CC4TT1..DD9014 1.98 2M 6798 10 0000....444455331587 11116555....1486 0.423 15.4 8888....32149602 7.74 2221....01486000 11119988....1556 1.75 19.9 33335545....1688 36.4 55556331....1809 54.7 12.24 21111110....72371666 2.94 272...723115 1.05 3M 1112 111354 00..448219 000...444433789 1111175555.....13549 88888.....6126111522 21..4837 221...213380 1111199988.....19046 3333355565.....35700 5555534531.....11809 111190111.....8667011587 21111.....6133550227 4M 1167 00..443529 1156..55 CTD Clo211tt089ed sample 000...443357307 111652...164 88..1556 11..9509 1199..13 3366..00 5533..06 1110..3122 01..9155 768...184394 1011...636878 111999...388 333652...199 555548...396 1122..3434 12.36 001...570189 APPENDIX 5 (Haematology - continued) MIN 313/023622 : 139 : Day 91 Group CExopmopsuourendlevel (ppm) 1 Con0trol 2 30 --P1O30S0F----- 4 300 G/rsoeuxp nAunmimbearl x10L9/L x10E9/L x10B9/L x1M09/L xL1U09C/L x1P0l9t/L sPeTc APseTcT 1M 2341 5 CC1TT80..DD2847 7.39 CC000TT...DD131120 CC000TT...DD000336 CCTT000...DD522278 CC000TT...DD210598 995CC253577TTDD CCC11TTT23..DDD82 CCC213TTT4..DDD19 2M 167980 179883.....8848113370 00000.....2111133986 00000.....0000133330 00000.....2343111790 00000.....1001056624 928628138 1910098 C11T34..D50 C11T56..D99 C1T4.D2 C1T6.D9 3M 1111113524 69998.....9870959672 00000.....1121219847 00000.....0000035242 00000.....2111238872 00000.....0000054467 1958800286814090 1111144433.....27696 2111137689.....13954 4M 2111106789 111181100.....7734113520 00000.....1100035997 00000.....0000035244 00000.....0111360704 00000.....1000013546 111981040505132786 13.2 11113242....5509 2211130677.....48002 CTD Clotted sample APPENDIX 5 (Haematology - continued) MIN 313/023622 : 140 : Day 91 Group : 1 CExopmopsouurendlevel (ppm) :: Con0trol 2 30 -- P1O30S0F---- 4 300 G/rsoeuxp nAunmimbearl Acyntoissois- Mcyitcorsois- Mcyatocrsois- chHroympoa-sia chHryopmears-ia 1M 2341 5 CT-D CT+D CT-D CT-D CT-D CT- D - CT++D CT- D - CT- D - CT- D - 2M 67 - ++ - - - 9O - + - - 10 - - - - - 3M 1111113524 --- ++- --- --- --- 4M 2111106789 ---- ---- ---- ---- ---- CTD Clotted sample APPENDIX 5 (Haematology - continued) : PI : Day 91 GCExoropmuoppsuourendlevel (ppm) : Con01trol 2 30 --P1O30S0F------ 4 300 G/rsoeuxp nAunmimbearl LH/cLt gH/dbL x1R0B1C2/L R%etic MCH pg MgC/dHLC MfCLV xW10B9C/L x1N09/L 1F 2222213245 CN000TS...D444321550 C111NT545S...D690 CN777TS...D692109 CN222TS...D008149 C211N0T99S...D476 C333N655TS...D382 C555N565TS...D028 C1NT671S...D117102 CN002TS...D891502 2F 2222367890 00000.....444441243213020 1111155454.....38708 77777.....9356633826 22211.....1445854952 2211100999.....14394 3333355555.....35884 5555554674.....52678 1178800.....9218215622 02011.....9892869060 3F 3333313245 00000.....444441202410448 1111144456.....92860 77777.....8741612460 24211.....0169828284 2221100099.....55172 3333355665.....14078 5555544757.....34484 196884.....7902354788 03111.....6441484555 4F 3333467890 00000.....444444233133777 1111155555.....68924 77788.....5880422982 22111.....0127631520 2111109989.....85594 3333365656.....37284 5555538423.....32076 1179810.....7643356489 00111.....6995270207 NCTSD CNlootstaemd psalemopbletained MIN 313/023622 APPENDIX 5 (Haematology - continued) MIN 313/023622 : 142 : Day 91 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol 2 30 -- P1O30S0F-- 4 300 G/rsoeuxp nAunmimbearl x10L9/L x10E9/L x10B9/L x1M09/L xL1U09C/L x1P0l9t/L sPeTc APseTcT 1F 2222213245 CN49T5S...D808447 CN000TS...D111627 CN000TS...D000132 CNT000S...D121559 CN000TS...D001540 11910C358N760TSD C111NT343S...D356 C111NT931S...D132 2F 2222367890 76658.....5177437070 00000.....2110335596 00000.....0000012222 00000.....2324115609 00000.....0011155029 999985740915867 CC111TT333...DD355 CC2110TT87...DD146 3F 3333313245 166850.....9331115970 00000.....1103104709 00000.....0000013226 00000.....2013238962 00000.....0000054686 998883458318489 1111134443.....16467 2111107467.....14947 4F 3333467890 66888.....7673798492 00000.....2021115426 00000.....0000013322 00000.....3110152496 00000.....0010055046 111981015580035658 NCSTD NColotstaemdpslaemopbletained 1111133222.....32948 2111108956.....33286 APPENDIX 5 (Haematology - continued) MIN 313/023622 : 143 : Day 91 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl Acyntoissois- 1F 2222213245 CT- D N-S - 2F 2222367890 --- 3F 3333313245 --- 4F 3333467890 --- NCSTD CNlootstaemd psalemopbletained 2 30 -- P1O30S0F-- Mcyitcorsois- Mcyatocrsois- CT-D CT-D N-S N-S ----- ------- ------- ---- 4 300 chHroympoa-sia CT- D N-S ------- chHryopmears-ia CT- D N-S ------- APPENDIX 5 (Haematology - continued) : ppi : Day 121 Group 1 CExopmopsuourendlevel (ppm) : Con0trol 2 30 --P1O30S0F------ 4 300 G/rsoeuxp nAunmimbearl LH/cLt gH/dbL x1R0B1C2/L R%etic MCH pg MgC/dHLC MfCLV xW10B9C/L x1N09/L 1M 44441324 45 00000.....433444981113882 1111156545.....13356 77778.....3939314892 2222....62946744 1.99 2211100998.....54874 3333377786.....14449 4555593325.....36062 11199013.....3187802276 0021....07821844 3.27 2M 4444567890 00000.....334349709009644 111434...598 1144..89 77778.....4304733344 23221.....7591859777 111998...504 1199..92 3333376676.....28478 5555521022.....57692 179983.....5495230896 22201.....5759518887 3M 5555513524 00000.....443441191136998 1111155455.....20944 77777.....7549613648 22222.....8206039792 2211100999.....11784 3333367666.....33689 5555553224.....39984 2107984.....8839430822 70111.....9354835459 4M 6555506789 00000.....344449113113590 1111154556.....13550 77788.....6391157007 22222.....7343237867 1111199999.....14667 3333377666.....35578 5555520333.....59086 111193001.....9139238478 4.02 3111....30625354 MIN 313/023622 APPENDIX 5 (Haematology - continued) MIN 313/023622 : 145 : Day 121 Group : 1 CExopmopsuourendlevel (ppm) :: Con0trol 2 30 -- P1O30S0F-- 4 300 G/rsoeuxp nAunmimbearl x10L9/L x10E9/L x10B9/L x1M09/L xL1U09C/L x1P0l9t/L sPeTc APseTcT 1M 44441324 45 179780.....5880194826 00000.....1112133008 00000.....0000013346 0000....33220272 0.15 00000.....2222013869 111981009624230508 1111123232.....90628 2221110075.....24967 2M 4444567890 165850.....8652013166 00000.....1000038777 00000.....0000013224 00000.....2113110666 00000.....1111011156 111880102824217978 C11T34..D84 1134..52 C21110T777....D0596 3M 5555513524 1166722.....1395511579 00000.....1301110904 00000.....0000068224 00000.....1141215862 00000.....3001016609 797989186790909 1111144534.....56299 1111144659.....11379 4M 6555506789 79888.....8320511002 00000.....1202058799 00000.....0000033352 00000.....2102194749 00000.....1100139980 11999000236933588 1111133433.....86408 14.7 11116485....1350 CTD Clotted sample APPENDIX 5 (Haematology - continued) : 9PI : Day 121 Group : 1 CExopmopsouurendlevel (ppm) :: Con0trol 2 30 -- P1O30S0F---- 4 300 G/rsoeuxp nAunmimbearl Acyntoissois- Mcyitcorsois- Mcyatocrsois- chHroympoa-sia chHryopmears-ia 1M 44441324 45 -- ++++-+ -- -- -- 2M 4444567890 +-- + +++-+ --- --- --- 3M 5555513524 --- +-- --- --- --- 4M 6555506789 ---- ++--- ---- ---- ---- MIN 313/023622 APPENDIX 5 (Haematology - continued) MIN 313/023622 : 147 : Day 121 GCExoropmuoppsuourendlevel (ppm) : Con01trol 2 --PO3SF------ 4 30 100 300 G/rsoeuxp nAunmimbearl LH/cLt gH/dbL x1R0B1C2/L R%etic MCH pg MgC/dHLC MfCLV xW10B9C/L N x109/L 1F 66661245 0.377 000...433099152 11114444....7978 7.04 777...212592 2211....73991470 20.3 222000...376 37.8 333777...760 53.6 555445...906 8.85 678...967122 0011....99451299 2F 6666767890 C0000T....D434308083789 C1111T5454....D3846 C7777T....D33734662 22111.....0299832880 C221100T99....D1889 C33338877T....D0274 C55552243T....D5592 CT4665....D88955507 C0002T....D77841108 3F 777132 7745 000...333698354 111354...827 00..341049 1115..64 677...853076 222...324060 221009...309 333888...302 555322...322 67..0027 21..2975 2119..73 3377..16 5527..18 74375.....1261111558 111...301940 01..3446 4F 7777867890 00000.....433341679135572 1111155345.....38400 7677....43901042 7.51 2222....41163582 1.76 2221101099.....37439 3333386777.....47292 5555562334.....66468 4374....14531542 6.95 00011.....5355449826 CTD Clotted sample APPENDIX 5 (Haematology - continued) MIN 313/023622 : 148 : Day 121 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol 2 -- PO3SF-- 4 30 100 300 G/ rsoeuxp nAunmimbearl L x109/L E x109/L B x109/L M x109/L xL1U09C/L x1P0l9t/L PT sec APTT sec 1F 66661245 7475....34855446 0.12 000...021776 0.02 000...000132 0.23 000...211199 0.12 947 000...101197 1881670977 13.7 111332...136 11117875....1840 2F 6666767890 C343T5....D79573474 C0000T....D10011989 C0000T....D00001112 CT0000....D11121046 C0000T....D01016066 16780C89071567TD C11113T333....D1794 C1111T6866....D8779 3F 777132 7745 325...499150 000...010507 000...000111 000...010529 000...000384 645976124 25..6699 00..0172 00..0002 00..2014 00..1056 889000 C1111T4344....D6872 C11T75..D77 1198..34 4F 7777867890 32355.....9363133290 00000.....0100159962 00000.....0000011110 00000.....1000138474 00000.....1010104862 748884376215598 C111T342...D389 C2113T58...D466 13.8 17.5 CTD Clotted sample APPENDIX 5 (Haematology - continued) MIN 313/023622 : 149 : Day 121 GCExoropmuoppsouurendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl Acyntoissois- 1F 66661245 -- 2F 6666767890 -CTD - 3F 777132 7745 4F 7777867890 ------ CTD Clotted sample 2 30 Mcyitcorsois --CTD +----- -- PO3SF---100 Mcyatocrsois- --CTD ------ 4 300 chHroympoa-sia --CTD ------ Hyperchromasia --CTD ------ APPENDIX 6 Biochemistry - individual values MIN 313/023622 : 150 : Day 91 GCExoropmuoppsuourendlevel (ppm) Con01trol 2 30 --P1O30S0F--- 4 300 G/rsoeuxp nAunmimbearl AUL/LP ALT U/L AST U/L LDH LDH1 LDH2 LDH3 LDH4 LDH5 TUo/tLal U/L U/L U/L U/L U/L 1M 1 234 5 221111658970068 4443539622 119908211248 1622119353731246 361108177 231197722 21 2364 5 21 616575 925113095986326 2M 6 17980 222231911530284 61 64575768 211113051053549 187 1233060876448 21 23231847 13 41113947 5 38788 12 136 72111355 238140890897 3M 1112 111354 232232056482942 6466536426 117984036768 514772 222941579 5111140647 311111192 117675 21116225 422113404709633 APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 151 : Day 91 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl TCUoP/tLKal 1M 23451 241119228784974 2M 167980 7322118225820726 3M 1111113524 231112354438594 2 30 -- P1O30S0F-- SUD/LH ^mBoilli/L 4 300 mUmroela/L 17.2 11114824....3804 22111 1124..39 111601...672 22111 11198512.....55764 22111 5.90 8555....60421276 76755.....5138892767 66555.....5500835722 ^Cmroela/tL 47 55551556 4555513944 4445513665 mGmloulc/L 6.62 6755....77473558 46555.....2682013287 65555.....0556609880 mCmhooll/L 1.70 11..3257 11..1708 01..9297 001...693179 00011.....7694015329 mTmroigl/L 0.55 00..2432 00..7236 00000.....2432415500 00000.....3234435568 mmNoal/L 145 111144440224 114454 111444564 111114444435626 APPENDIX 6 (Biochemistry - continued) Day 91 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol 2 30 --P1O30S0F------ 4 300 G/rsoeuxp nAunmimbearl mmKol/L mmColl/L mmCoal/L mPmhools/L Totga/lLProt Ag/lLb ga/Ll ga/2L Bge/Lta MIN 313/023622 : 152 : 1M 23451 4.0 3335....1768 2M 167980 34433.....50086 3M 1111113524 43443.....59409 INS Insufficient sample 107 111100005666 111110100078068 111110000106786 2.79 22..5772 22..6684 22211.....2117933400 61 66662454 22222.....7766704274 22211.....0029907479 6667638580 22222.....7877774727 2.20 2222....00223888 6766613055 29 12 4 12 232IN908 S I11N922S IN333S I1N4S 1157 3323312090 1111132020 34 333 1111155772 3322322890 1111133302 33433 12 11116244 APPENDIX 6 (Biochemistry - continued) Day 91 GCExoropmuoppsouurendlevel (ppm) ::: Con01trol G/ rsoeuxp nAunmimbearl Gamma g/L 2 30 -- P1O30S0F-- RAa/tGio A%lb 4 300 a%l a%2 B%eta Gam%ma MIN 313/023622 : 153 : 1M 23451 4 0.91 47.7 20.1 5.8 19.5 6.8 IN675S IN000...S887368 444IN554...S674 I111N984...S155 IN4.S4 44..57 222IN316...S160 I1N970...S396 2M 167980 176605 00001.....8787064940 4444465229.....78696 1111177685.....12099 44345.....47876 2222231340.....15047 1199840.....35502 3M 1111113524 4 6664 00001.....8888114060 4444555462.....11277 1111196889.....57876 44645.....15587 2222122019.....33286 169680.....50680 INS Insufficient samples APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 154 : Day 91 GCExoropmuoppsuourendlevel (ppm) Con01trol 2 30 --P1O30S0F--- 4 300 G/rsoeuxp nAunmimbearl AUL/LP AUL/LT AUSLT TLUoD/tLHal LUD/HL1 LUD/HL2 LUD/HL3 LUD/HL4 LUD/HL5 4M 2111106789 333326409266294 6665838627 1119902011650 222217865306889 2111161552 1111148067 96766 1112 11794 22220223814627 APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 155 : Day 91 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl TCUoP/tLKal 4M 2111106789 211115732485747 2 30 -- P1O30S0F-- SUD/LH ^mBoilli/L 4 300 mUmroela/L 1111103221.....17274 11111 66677.....5163297847 ^Cmroela/tL 4444556882 mGmloulc/L 65555.....4208776789 mCmhooll/L 00001.....9465511404 mTmroigl/L 00000.....0112555794 mmNoal/L 111114444413542 APPENDIX 6 (Biochemistry - continued) : 9SI : Day 91 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol 2 30 --P1O30S0F------ 4 300 G/rsoeuxp nAunmimbearl mmKol/L mmColl/L mmCoal/L mPmhools/L Totga/lLProt Ag/lLb ga/Ll ga/2L Bge/Lta 4M 2111106789 44434.....13904 111110000055686 22222.....8787711329 22211.....0119928042 6677657020 3333254657 1112 111134 23333 1124 111354 MIN 313/023622 MIN 313/023622 : 157 : APPENDIX 6 (Biochemistry - continued) Day 91 GCExoropmuoppsouurendlevel (ppm) ::: Con01trol G/ rsoeuxp nAunmimbearl Gamma g/L 2 30 -- P1O30S0F-- RAa/tGio A%lb 4 300 a%l 4M 2111106789 66744 00111.....9801053276 4455585300.....10826 1111188688.....56908 a%2 B%eta Gam%ma 34..15 335...179 2211104988.....51959 168850.....54690 APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 158 : Day 91 GCExoropmuoppsuourendlevel (ppm) Con01trol 2 30 --P1O30S0F--- 4 300 G/rsoeuxp nAunmimbearl AULLP AUL/LT AUS/LT TLUoD/tLHal LUD/HL1 LUD/HL2 LUD/HL3 LUD/HL4 LUD/HL5 1F 2222213245 197 111382N398S 43 121 780 334N602S 1776N650S 325511N546S 40 21N994S 41 31N997S 21N4585S 42 643 31N919S 331808N514S 2F 2222367890 116478 11932569 3492 379136 1117803485424 222116158619493 1111111392 2111133200 213 1058 11162228 213122 211162896 3F 3333313245 11119162137777 12233189856 17798910950 321110564659337 1111113502 11137926 74378 1113667 221115013219989 NS No sample Animal 23 died at bleed APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 159 : Day 91 GCoromuppound :: Con1trol Exposure level (ppm) : 0 2 --PO3SF------ 4 30 100 300 G/ rsoeuxp nAunmimbearl CPK TUo/tLal SDH U/L ^mBoilli/L mUmroela/L 1F 2222213245 126119285N1852S 111N9427S....4586 N2222S N9768S....82003097 2F 26 200 22237890 111010 110410 11.4 1119109....1094 32332 6.86 6678....18805808 3F 3333313245 111115010857602 11179140.....19287 22222 76655.....0333916890 NS No sample Animal 23 died at bleed ^Cmroela/tL 7665N3499S 57 65552568 6555530554 mGmloulc/L N4466S....15403920 6.38 4665....89961135 66675.....4823477708 mCmhooll/L N2221S....33083586 22221.....5547602294 22111.....2999518960 mTmroigl/L N0000S....47581162 0.36 0000....34533308 00000.....4343535502 mmNoal/L 11114444N1332S 111444124 114455 111114444411344 APPENDIX 6 (Biochemistry - continued) Day 91 GCoromuppound :: Con1trol 2 --PO3SF------ 4 Exposure level (ppm) : 0 30 100 300 Group / sex nAunmimbearl mmKol/L mmColl/L mmCoal/L mPmhools/L Total Prot g/L Alb g/L a1 g/L a2 Beta g/L g/L MIN 313/023622 : 160 : 1F 2222213245 N4333S....1424 11110000N5566S N2222S....79875009 N1111S....48729894 7767N1118S 3333N7757S 1111N1000S N4343S 1111N3444S 2F 26 3.4 106 22237890 3333....1502 111100007876 2.85 1.43 75 2322....60889006 1111....55361089 77771369 43 34431429 1111111102 4 14 3345 1154 1133 3F 3333313245 22333.....89220 111110000035747 22222.....8768633848 11111.....6574513278 7677634527 3343384086 1111111000 43443 1111133444 NS No sample Animal 23 died at bleed APPENDIX 6 (Biochemistry - continued) : 191 : Day 91 GCoromuppound :: Con1trol Exposure level (ppm) : 0 G/ rsoeuxp nAunmimbearl Gamma g/L 2 -- PO3SF-- 30 100 A/G Alb Ratio % 4 300 al % a2 Beta Gamma %%% 1F 2222213245 N7675S N1111S....00009969 5555N2112S....1882 1111N5443S....4288 N4455S....1862 2211N0089S....0909 1N9780S....2290 2F 26 5 22237890 9965 1.34 57.2 01..9224 11..0158 45557424....5580 1111134534.....58646 4.7 44..15 55..70 18.1 21110697....8509 1166822.....55540 3F 3333313245 66485 11111.....2011116026 5555530342.....35908 1111153445.....59709 44555.....13940 2111109988.....23572 177761.....96762 NS No sample Animal 23 died at bleed MIN 313/023622 APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 162 : Day 91 GCExoropmuoppsuourendlevel (ppm) Con01trol 2 30 --P1O30S0F--- 4 300 G/rsoeuxp nAunmimbearl AULLP AUL/LT AUS/LT TLUoD/tLHal LUD/HL1 LUD/HL2 LUD/HL3 LUD/HL4 LUD/HL5 4F 3333467890 1119942624242 2434888450 117991435859 324212882955727 6111146246 5111114547 162855 211131640 217532 231537108 APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 163 : Day 91 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl TCUoP/tLKal 4F 3333467890 11119359267879 2 30 -- P1O30S0F-- SUD/LH ^mBoilli/L 4 300 mUmroela/L 1111126655.....59866 22221 177582.....6713733552 ^Cmroela/tL 6755511458 mGmloulc/L 66555.....9264215760 mCmhooll/L 11..6954 221...128777 mTmroigl/L 00000.....4342413982 mmNoal/L 111114444413444 APPENDIX 6 (Biochemistry - continued) : P9 : Day 91 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol 2 30 --P1O30S0F------ 4 300 Group Animal K Cl Ca Phos Total Prot Alb al a2 Beta / sex number mmol/L mmol/L mmol/L mmol/L g/L g/L g/L g/L g/L 4F 4333306789 33333.....22484 111110000054464 22222.....8777837680 11111.....4865611157 7777835482 4444450220 1111111222 44333 1111113346 MIN 313/023622 : 591 : APPENDIX 6 (Biochemistry - continued) Day 91 GCExoropmuoppsouurendlevel (ppm) ::: Con01trol G/ rsoeuxp nAunmimbearl Gamma g/L 2 30 -- P1O30S0F-- RAa/tGio A%lb 4 300 a%l 4F 3333467890 96655 11111.....2322011527 5555544561.....57878 1111164545.....36049 a%2 B%eta Gam%ma 43445.....79408 2111105586.....85679 177770.....15707 MIN 313/023622 APPENDIX 6 (Biochemistry - continued) Day 121 GCExoropmuoppsuourendlevel (ppm) 1 Con0trol 2 30 --P1O30S0F--- 4 300 : 991 : G/rsoeuxp nAunmimbearl ALP U/L 1M 41 172 42 4434 210483 198 45 187 2M 46 178 47 240 48 268 49 50 223514 3M 51 171 5532 223090 5554 214206 ALT U/L AST U/L LDH TUo/tLal LDH1 U/L LDH2 U/L LDH3 U/L LDH4 U/L LDH5 U/L 43 84 205 1132 16 10 25 7 22 17 112094 4309 6767 115419 11 10 10 8 241 2125 109 130 43 76 189 34 67 205 10 9 11 21 154 56 99 200 51 85 241 74 133 140 50 95 129 49 87 100 21 11 193 1132 180 14 7 66 4 6 3 1157 144 200 11 12 18095 7 70 13 9 3 10 92 49 84 127 4532 8868 112537 111692 182 8 4 3 8 14 114 9 80 10 85 3674 9815 124 236 14 15 9 26 171 MIN 313/023622 MIN 313/023622 : 167 : Day 121 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl TCUoP/tLKal 1M 4444413245 431113550514827 2M 4444567890 118484 21093506 3M 5555513524 23117418011492 APPENDIX 6 (Biochemistry - continued) 2 30 -- P1O30S0F-- SUD/LH ^mBoilli/L 4 300 mUmroela/L 17.1 1119300....5686 22211 1111112454.....17904 22211 211107123.....16620 20211 5.10 4455....75013270 66655.....2038233370 46655.....7724354099 ^Cmroela/tL 48 44551960 4445556940 4445599602 mGmloulc/L 5.80 6755....71856764 66758.....9939513089 76665.....6773215499 mCmhooll/L 1.54 2111....45250598 01111.....5032295544 1.24 0011....98503484 mTmroigl/L 0.33 0000....55255470 00000.....3533335264 00000.....3344317077 mmNoal/L 142 111144443322 111114444413422 111114444422242 APPENDIX 6 (Biochemistry - continued) Day 121 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol 2 30 --P1O30S0F------ 4 300 G/rsoeuxp nAunmimbearl mmKol/L mmColl/L mmCoal/L mPmhools/L Totga/lLProt Ag/lLb ga/1L ga/2L Bge/Lta : 891 : 1M 4444413245 2M 4444567890 3M 5555513524 4.1 102 3343....5628 110012 110032 33433.....19888 111110000033422 4.1 102 3343....1559 111100003324 2.62 2222....65651844 11111.....8798604046 66 66663658 32 32332922 11 11111132 22222.....6665555088 11111.....7865806207 6666635522 2322219699 11111990 22222.....5655511526 11111.....8747813597 6665532589 2222298788 111190020 45555 1111135544 45 855 1111135664 4 14 3444 11113644 MIN 313/023622 APPENDIX 6 (Biochemistry - continued) Day 121 GCExoropmuoppsuourendlevel (ppm) ::: G/rsoeuxp nAunmimbearl Con01trol Gamma g/L 2 30 -- P1O30S0F-- 4 300 RAa/tGio A%lb a%l a%2 B%eta Gam%ma : 691 : 1M 4444413245 2M 4444567890 3M 5555513524 44263 45 645 44855 0.94 48.1 0001....89801349 4474..86 4570..52 111698...344 1167..15 7.7 7758....6290 2222221210.....74708 5.2 6358....3574 00000.....8968817788 4434464896.....50849 1111147644.....33584 176882.....33574 2222234141.....35589 76968.....13907 00000.....8788986700 4444463658.....96222 1111164597.....59870 66655.....39969 2222231431.....38202 177671.....99209 MIN 313/023622 APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 170 : Day 121 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol 2 -- PO3SF-- 4 30 100 300 G/rsoeuxp nAunmimbearl AUL/LP ALT U/L AST U/L LDH LDH1 LDH2 LDH3 LDH4 LDH5 TUo/tLal U/L U/L U/L U/L U/L 4M 56 57 224286 192 206 228 52 83 146 58 219 39 82 191 59 318 56 92 166 60 208 85 129 266 15 10 1113 8 8 1194 174 103 1137 1154 78 1155 113166 29 20 11 32 174 APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 171 : Day 121 GCExorpomuoppsuourendlevel (ppm) ::: 1 Con0trol G/rsoeuxp nAunmimbearl TCUoP/tLKal 4M 6555506789 321016943 347054 2 30 -- P1O30S0F-- SUD/LH ^mBoilli/L 4 300 mUmroela/L 321161826.....16464 211 11 46555.....2631556082 ^Cmroela/tL 445184 4560 mGmloulc/L 65555.....3106133409 mCmhooll/L 1.42 1111....25335802 mTmroigl/L 000...423155 00..4139 mmNoal/L 144 114434 114454 APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 172 : Day 121 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol 2 30 --P1O30S0F------ 4 300 G/rsoeuxp nAunmimbearl mmKol/L mmColl/L mmCoal/L mPmhools/L Totga/lLProt Ag/lLb ga/1L ga/2L Bge/Lta 4M 6555506789 33334.....89809 111110000033333 22222.....6656659782 11111.....9678713586 6666636694 2323313929 1111111132 45555 1154 111334 MIN 313/023622 : 173 : APPENDIX 6 (Biochemistry - continued) Day 121 GCExoropmuoppsuourendlevel (ppm) ::: Co10ntrol G/ rsoeuxp nAunmimbearl Gamma g/L 2 30 ------ P31O0S0F------ 4 300 RAa/tGio A%lb a%1 4M 56 65550789 6 45 45 0.78 44.4 0000....89995424 44446878....5087 1111176897.....12742 a%2 B%eta Gam%ma 7.0 6775....3962 222121...346 2200..96 9.0 7665....3289 APPENDIX 6 (Biochemistry - continued) Day 121 GCExoropmuoppsuourendlevel (ppm) Con01trol 2 30 --P1O30S0F--- 4 300 G/rsoeuxp nAunmimbearl AUL/LP ALT U/L AST U/L LDH Total U/L LDH1 U/L LDH2 U/L LUD/HL3 LDH4 U/L LUD/HL5 MIN 313/023622 : 174 : 1F 61 106 48 84 140 6624 157 105 26 157 67 298 44896 65 100 38 67 161 2F 66 112 46 89 437 67 65 123 291 392 6689 110259 70 65 3434 35 9802 66 62518138 3F 71 90 31 77 226 7732 110017 3384 18109 428488 7745 19265 6208 7669 21851 4F 76 77 18014 63 34 108 64 218114 78 123 38 98 239 79 80 114113 48 38 88 431 74 176 11 8 7 11 104 N1R3 N1R0 N3R N7R N5R4 10 10 10 21 398 13 10 13 14 112 1150 13 260 6 1150 3 31410 335566 62 1115 11 8 12 8 4171 566 176 15 23 7 19 161 4110 188 394 13 9 8 7 4 5 1111 212 50 14 7 6 14 174 11 7 9 7 7 3 162 251 82 24 12 198 64 22 20 318669 16 14 10 20 116 APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 175 : Day 121 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl TCUoP/tLKal 1F 66661245 1177418772 2F 6666767890 22118372256759 3F 7777713245 91114282433298 4F 7777867890 21113762583900 2 -- PO3SF-- 30 100 SUD/LH ^mBoilli/L 4 300 mUmroela/L 31114505....1778 2233 2111163076.....72890 22211 14.6 1118523....3989 22222 5111178160.....65929 21111 7675....38291694 67555.....3674858778 66655.....8433635582 67685.....0618656268 ^Cmroela/tL 65554887 6555525649 6555514559 6555595894 mGmloulc/L 7768....30175286 66778.....0671313422 77765.....6699155586 67975.....6719729797 mCmhooll/L 2321....35585424 22311.....5725778957 1.27 0221....76861726 111...899392 31..4731 mTmroigl/L 0001....41405394 00000.....5644435946 00000.....5233558200 00000.....4346455049 mmNoal/L 111144431008 111114444411132 142 111144443022 111114444413352 APPENDIX 6 (Biochemistry - continued) MIN 313/023622 : 176 : Day 121 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol 2 -- PO3SF-- 4 30 100 300 G/ rsoeuxp nAunmimbearl mmKol/L mmColl/L mmCoal/L mPmhools/L Total Prot g/L Alb g/L a1 g/L a2 Beta g/L g/L 1F 66661245 3333....3522 111100000200 2F 6666767890 33233.....35697 111110000011342 3F 7777713245 33333.....37222 111110000013333 4F 7777867890 33333.....55496 111000442 110037 2222....79781000 1111....83465466 77773524 44341374 19908 22222.....8666828684 11111.....3253113644 6677789008 3333485992 119988 22222.....7657513556 11111.....4560432447 6667767828 3334467500 11119008 22222.....7867633206 21111.....0523953097 7677733070 3334388809 119798 4444 11115444 44455 1111133544 4 3334 1111133444 44455 1111133554 MIN 313/023622 : 177 : Day 121 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol G/ rsoeuxp nAunmimbearl Gamma g/L 1F 66661245 4655 2F 6666767890 47465 3F 7777713245 105555 4F 7777867890 37555 APPENDIX 6 (Biochemistry - continued) 2 -- PO3SF-- 30 100 RAa/tGio A%lb 4 300 a%1 1111....32044867 55551769....3762 11111.....0222137667 5555555054.....15682 11111.....2202035506 5555515451.....35242 11111.....3211111599 5555544463.....33904 11113220....1804 1111121234.....09947 12.6 11115353....3422 1111131124.....11284 a%2 B%eta Gam%ma 5555....6092 21110898....8947 7965....5000 67455.....90988 2211100979.....36392 69775.....12929 44455.....56070 2111109998.....19794 177762.....55064 67645.....17686 2211110898.....79840 74669.....56684 APPENDIX 7 Urinalysis - individual values Day 29 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol 2 30 G/rsoeuxp nAunmimbearl App. Vmoll -- P1O30S0F-- PH 4 300 SG g/L Prot Gluc Keto g/L Bili Blood MIN 313/023622 : 178 : 1M 8812 888354 MMPPPYYYYY 44..20 345...806 4M 88886789 90 MMMPPYYYYY 4232....0046 4.6 1F 9999913245 MMPPPYYYYY 2.6 3245....4408 4F 19999067890 MMMMPYYYYY 22421.....02828 66666.....58766 11111000004943412247 6666....5226 1074 111000476642 6.6 1039 6.3 6666....1556 11111000004353416095 66665.....12207 11002704 111000348306 01111.....7042111899 00000 TTT00RRR 00000 00111.....9904237540 0000 0 TTTTTRRRRR 0000 0 00000.....4543456220 0 0000 0 0000 0 0000 00000.....4463466904 00000 00000 00000 00000 0000 0 0 0000 00000 MIN 313/023622 : 179 : APPENDIX 7 (Urinalysis - continued) Day 29 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol 2 30 G/rsoeuxp nAunmimbearl Epi Leuc -- P1O30S0F-- RBC 4 300 Cryst Sperm 1M 88881324 85 0001 0 00001 00000 00000 00111 4M 9888806789 00000 00000 00000 00000 002 01 1F 9912 999345 00001 00011 00000 00000 00000 4F 19999067890 00011 00000 00000 00000 00000 Casts 00000 00000 00000 00000 Abn. Nma mTootlal KmTmootal l 00000 00000.....7243556070 01111.....8334110209 00000 00000.....2213639644 00011.....7931135560 00000 00000.....3343414894 00000.....5594844768 00000 00000.....1221313079 00000.....5567757082 APPENDIX 7 (Urinalysis - continued) Day 29 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol 2 30 G/rsoeuxp nAunmimbearl Cml Tmootlal mUm-Nola/L ----- PO130S0F-- U-K mmol/L 4 300 mUm-oCl/lL MIN 313/023622 : 180 : 1M 8888813524 00..4219 000...353982 116993264634.....11575 332223931327114.....55000 71.4 1198007031....1367 4M 9888806789 00000.....3124335690 17798339879.....59954 221323176995660...550 114.2 177805635....3529 1F 9999913245 00000.....2223359946 1119836012922.....16047 211120569289071....5500 119850104932....110.22 4F 19999067890 00000.....2113213974 9779868360.....34447 232318325624721.....55550 117780017458.....33867 APPENDIX 7 (Urinalysis - continued) : 181 : Day 91 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl App. 1M 21 345 CCCCPMMMPYYYYY 2M 167980 CCCCMPPPYYYY CMY 3M 1111113524 CCCCCPPPPPYYYYY 2 30 -- P1O30S0F---- 4 300 Vmoll PH SG g/L 194642.....02204 77677.....80784 11111000003443211372 67424.....88882 77777.....11527 11003662 11003422 1049 97658.....04220 77666.....35297 11111000003333410964 Prot Gluc g/L 00011.....5961438470 00000 01..6122 01..9407 0.91 00000 00000.....9878912094 00000 Keto TTT00RRR TTTTRRRR TR TTT+RRR TR Bili Blood 00000 00000 00000 00000 00000 00000 MIN 313/023622 MIN 313/023622 : 182 : APPENDIX 7 (Urinalysis - continued) Day 91 GCExorpomuoppsuourendlevel (ppm) ::: G/rsoeuxp nAunmimbearl Con01trol Epi 2 30 -- P1O30S0F-- Leuc RBC 4 300 Cryst Sperm 1M 23451 0 0000 0 0001 0 0000 0 0000 1 0000 2M 167980 11 000 00000 00000 00000 00000 3M 1111113524 00000 00000 00000 00000 00211 Casts 0 0000 00000 00000 Abn. Nma mTootlal KmTmootall 0 0.66 1.63 0000 00..3442 00..2999 0011....99453394 00000 00000.....5341602464 01111.....8224411359 00000 00000.....2765235888 1.28 1111....55037476 APPENDIX 7 (Urinalysis - continued) Day 91 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl Cml Tmootlal 2 30 --P1O30S0F------ 4 300 mUm-Nola/L mUm-oKl/L mUm-oCl/lL MIN 313/023622 : 183 : 1M 23451 2M 167980 3M 1111113524 0.68 73.8 181.0 76.1 0000....54481159 67787292....0969 222133325143....5000 1178002272....3059 00000.....3245438876 17142..15 1355361...647 222218195973071.....50000 116663072951.....15046 00000.....8653311988 16385046440.....57867 221110667781043.....50000 17667112650.....11369 APPENDIX 7 (Urinalysis - continued) MIN 313/023622 : 184 : Day 91 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl App. 4M 2111106789 CCCCCMMMPPYYYYY 2 30 -- P1O30S0F---- 4 300 Vmoll PH SG g/L 62253.....28820 66666.....87764 11111000004466733680 Prot Gluc g/L 00111.....9716410204 00000 Keto TTTTTRRRRR Bili Blood 00000 00000 MIN 313/023622 : 185 : APPENDIX 7 (Urinalysis - continued) Day 91 GCExorpomuoppsuourendlevel (ppm) ::: G/rsoeuxp nAunmimbearl 1 Con0trol Epi 2 30 -- P1O30S0F-- Leuc RBC 4 300 Cryst Sperm 4M 16 0 0 0 0 0 21110789 0000 0000 0000 0000 0211 Casts 0 0000 Abn. Nma mTootlal KmTmootall 0 0.58 0.77 0000 0000....53315062 0111....71303964 APPENDIX 7 (Urinalysis - continued) : 981 : Day 91 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl Cml Tmootlal 2 30 --P1O30S0F------ 4 300 mUm-Nola/L mUm-oKl/L mUm-oCl/lL 4M 2111106789 00000.....2461339088 210638059985.....68948 222237841262770.....55500 19985347396.....32070 MIN 313/023622 APPENDIX 7 (Urinalysis - continued) Day 91 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl App. 2 30 -- P1O30S0F---- 4 300 Vmoll pH SG g/L Prot Gluc Keto g/L Bili Blood MIN 313/023622 : 187 : 1F 2222213245 MPPPPYYYYY 3.2 2851....6088 6.6 1033 6666....9664 1111000035231097 0.14 0 0000....21128642 0000 0 0000 0 0000 0 0000 2F 2222367890 CPPPPPYYYYY 42634.....06088 66676.....64826 11004404 111000323294 00000.....2121235980 00000 00000 00000 00000 3F 3333313245 MMMPPYYYYY 22234.....06002 66666.....35264 11111000004566490442 00000.....3222213560 00000 00000 00000 00000 : 881 : APPENDIX 7 (Urinalysis - continued) Day 91 GCExorpomuoppsuourendlevel (ppm) ::: G/rsoeuxp nAunmimbearl Con01trol Epi 2 30 -- P1O30S0F-- Leuc RBC 4 300 Cryst Sperm 1F 2222213245 0 0000 1 0000 0 0000 0 0000 0 0000 2F 2222367890 00000 00000 00000 00000 00000 3F 3333313245 00000 00000 00000 00000 00000 Casts 0 0000 00000 00000 Abn. Nma mTootlal KmTmootall 0 0.20 0.55 0000 00..3152 00..4736 0000....29593580 00000 00..4242 000...342372 00000.....4757733578 00000 00000.....2221235098 0.41 0000....95673549 MIN 313/023622 APPENDIX 7 (Urinalysis - continued) Day 91 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl Cml Tmootlal 2 30 --P1O30S0F------ 4 300 mUm-Nola/L mUm-oKl/L mUm-oCl/lL : 681 : 1F 2222213245 2F 2222367890 3F 3333313245 0.27 63.9 171.0 83.6 0000....13531487 169737434....5480 211122151995....5500 167633342....4065 00..3204 000...333379 17488085579.....24592 111119624624413.....55000 7968843170.....49884 00000.....2222311154 9999527654.....35698 222226047243761.....50000 1116800102364.....35024 MIN 313/023622 APPENDIX 7 (Urinalysis - continued) MIN 313/023622 : 190 : Day 91 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl App. 4F 3333467890 CMMMMMYYYYY 2 30 -- P1O30S0F---- 4 300 Vmoll pH SG g/L 22311.....60288 67666.....54262 11111000004487935480 Prot Gluc g/L 00000.....2233433900 00000 Keto 00000 Bili Blood 00000 00000 : 161 : APPENDIX 7 (Urinalysis - continued) Day 91 GCExorpomuoppsuourendlevel (ppm) ::: G/rsoeuxp nAunmimbearl Con01trol Epi 2 30 --P1O30S0F--- 4 300 Leuc RBC Cryst Sperm 4F 3333467890 00000 00001 00000 00000 00000 Casts 00000 Abn. Nma mTootlal KmTmootal l 00000 00000.....1221255804 00000.....7566635688 MIN 313/023622 APPENDIX 7 (Urinalysis - continued) MIN 313/023622 : 192 : Day 91 GCExorpomuoppsouurendlevel (ppm) ::: Con01trol 2 30 -- P1O30S0F--- 4 300 G/rsoeuxp nAunmimbearl Cml Tmootlal mUm-Nola/L mUm-oKl/L mUm-oCl/lL 4F 3333467890 00000.....2312213749 118553289771.....26808 243315074746620.....55550 11116013432544.....15979 APPENDIX 7 (Urinalysis - continued) Day 121 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl App. 2 30 -- P1O30S0F---- 4 300 Vmoll PH SG g/L Prot Gluc Keto g/L Bili Blood MIN 313/023622 : 193 : 1M 4444413245 CCCCPPPPPYYYYY 3.2 112820....0002 6.8 1033 6777....7622 1111000032235662 2M 4444567890 CCCCCMPPPPYYYYY 65458.....44888 76777.....10900 11111000003454333807 3M 5555513524 CCMMPPPYYYYY 29395.....60220 66666.....59976 11111000003453624868 1.07 0 0001....59705347 0000 TTT++RRR 0 0000 21111.....1002018822 00000 + TTTTRRRR 00000 00111.....8944112262 00000 TTTTTRRRRR 00000 0 000+ 00000 00000 MIN 313/023622 : 194 : APPENDIX 7 (Urinalysis - continued) Day 121 GCExorpomuoppsuourendlevel (ppm) ::: G/rsoeuxp nAunmimbearl Con01trol Epi 2 30 -- P1O30S0F-- Leuc RBC 4 300 Cryst Sperm 1M 4444413245 00001 00001 0 0001 0 0000 20221 2M 4444567890 00001 01 000 00000 00000 00111 3M 5555513524 00000 00000 00000 00000 20111 Casts 0 0000 00000 00000 Abn. Nma mTootlal KmTmootall 0 0.18 0.44 0000 0000....36504669 0111....37721724 00000 00000.....5645611529 11111.....2224013556 00000 00000.....2484555686 00111.....7822544502 APPENDIX 7 (Urinalysis - continued) Day 121 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl Cml Tmootlal 2 30 --P1O30S0F------ 4 300 mUm-Nola/L mUm-oKl/L mUm-oCl/lL MIN 313/023622 : 195 : 1M 4444413245 2M 4444567890 3M 5555513524 0.19 0000....44415942 4455524445.....50790 139.0 211124251324....5000 6634501737.....54407 00000.....4554355067 119950043948.....59672 213328..00 311089213...550 14888013064.....92070 00000.....3413513896 19996423541.....15464 222118633653959.....55500 6649817736.....13579 APPENDIX 7 (Urinalysis - continued) : 961 : Day 121 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl App. 4M 6555506789 MMPPPYYYYY 2 30 -- P1O30S0F---- 4 300 Vmoll pH SG g/L 58..84 463...022 66666.....85656 11111000004354616606 Prot Gluc g/L 00111.....9711086807 00000 Keto TTTTTRRRRR Bili Blood 00000 00000 MIN 313/023622 MIN 313/023622 : 197 : APPENDIX 7 (Urinalysis - continued) Day 121 GCExorpomuoppsuourendlevel (ppm) ::: G/rsoeuxp nAunmimbearl Con01trol Epi 2 30 --P1O30S0F--- 4 300 Leuc RBC Cryst Sperm 4M 6555506789 00000 00001 00000 00000 20111 Casts 00000 Abn. Nma mTootlal KmTmootal l 00000 00000.....2354235587 01111.....9602111824 APPENDIX 7 (Urinalysis - continued) : 861 : Day 121 GCExoropmuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl Cml Tmootlal 2 30 --P1O30S0F------ 4 300 mUm-Nola/L mUm-oKl/L mUm-oCl/lL 4M 6555506789 00000.....3352311558 6755880979.....35560 223111809605632.....55000 6677590646.....13099 MIN 313/023622 APPENDIX 7 (Urinalysis - continued) : 661 : Day 121 GCExorpomuoppsuourendlevel (ppm) ::: Con01trol G/rsoeuxp nAunmimbearl App. 1F 66661245 MPPPYYYY 2F 6666767890 MPPPPYYYYY 3F 7777713245 MMPPPYYYYY 4F 7777867890 MMMPPYYYYY 2 -- PO3SF---- 4 30 100 300 Vmoll PH SG g/L 6251....6446 6665....2029 1111000034343397 44465.....22200 66666.....24400 11111000004334319707 2.4 3241....2622 66666.....13002 11111000006464302076 33243.....08082 66666.....12422 11111000003446435707 Prot Gluc g/L 0000....32311708 0000 00000.....2122137809 00000 0.22 0000....13125489 00000 00000.....2122339867 00000 Keto 0000 00000 00000 00000 Bili Blood 0000 0000 00000 00000 00000 00000 00000 00000 MIN 313/023622 MIN 313/023622 : 200 : APPENDIX 7 (Urinalysis - continued) Day 121 GCExorpomuoppsuourendlevel (ppm) ::: G/rsoeuxp nAunmimbearl Con01trol Epi 2 -- PO3SF-- 30 100 Leuc RBC 4 300 Cryst Sperm 1F 66661245 0000 0001 0000 0000 0000 2F 6666767890 00001 00000 00000 00000 00000 3F 7777713245 00000 00000 00000 00000 00000 4F 7777867890 00000 00000 00000 00000 00000 Casts 0000 00000 00000 00000 Abn. Nma mTootlal KmTmootall 0000 0000....30311867 0000....83948672 00000 00000.....1342386069 00001.....9588019079 00000 00000.....0001386707 00000.....6664533344 00000 00000.....1212399640 00000.....6677633586 APPENDIX 7 (Urinalysis - continued) Day 121 Group : 1 CExopmopsuourendlevel (ppm) :: Con0trol G/rsoeuxp nAunmimbearl Cml Tmootlal 2 30 --P1O30S0F------ 4 300 mUm-Nola/L mUm-oKl/L mUm-oCl/lL MIN 313/023622 : 201 : 1F 6612 6645 2F 6666767890 3F 7777713245 4F 7777867890 0000....31021376 75552713....5529 211126475266....5550 44555064....9056 00000.....1352315248 4796623255.....39706 221110148568091.....55550 12685073633.....33358 00000.....0102350904 3358148679.....31498 232116649205378.....55550 4247808550.....89460 00000.....2221113028 6749822590.....13779 232111109616762.....50000 6645587505.....11184 MIN 313/023622 : 202 : APPENDIX 8 Absolute organ weights - individual values (g) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 GROUP 1M ANIMAL i 2 3 4 5 TERMINAL BODY WT (g) 500.7 421.8 457.3 433.8 449.6 BRAIN 2.14 2.03 1.98 1.99 1.94 ADRENALS 0.086 0.050 0.069 0.045 0.054 HEART 1.803 1.227 1.383 1.406 1.481 2M 6 7 8 9 10 509.2 403.3 478.1 433.0 424.9 2.06 1.90 2.16 2.01 2.01 0.063 0.052 0.047 0.060 0.046 1.554 1.282 1.428 1.514 1.105 KIDNEYS 3.00 2.46 2.55 2.44 2.52 LIVER 17.89 13.39 15.49 14.55 12.76 LUNGS & BR 1.673 1.384 1.467 1.601 1.474 2.92 2.23 2.74 2.66 2.48 15.57 12.30 17.33 13.52 14.12 1.668 1.264 1.510 1.498 1.397 Print No: 0026 Printed: 23-JUL-02 Xybion protocol number: MIN 313 MIN 313/023622 : 203 : APPENDIX 8 (Absolute organ weights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 GROUP 3M ANIMAL 11 12 13 14 15 TERMINAL BODY WT (g) 430.6 465.0 448.0 401.6 457.4 BRAIN 1.83 2.03 2.01 1.96 2.07 ADRENALS 0.055 0.050 0.065 0.047 0.060 HEART 1.557 1.492 1.270 1.166 1.415 4M 16 17 18 19 20 377.6 332.9 385.0 403.3 358.4 2.03 1.88 2.06 2.04 1.97 0.069 0.055 0.045 0.065 0.058 1.395 1.025 1.318 1.625 1.270 KIDNEYS 2.40 3.18 2.82 2.48 3.04 LIVER 14.24 17.99 17.26 14.91 16.94 LUNGS & BR 1.450 1.540 1.561 1.366 2.043 2.72 2.15 2.63 2.51 2.23 16.91 16.77 19.38 20.97 18.03 1.878 1.765 2.044 2.131 2.077 Print No: 0026 Printed: 23-JUL-02 Xybion protocol number: MIN 313 MIN 313/023622 : 204 : APPENDIX 8 (Absolute organ weights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 GROUP 1F ANIMAL 21 22 24 25 TERMINAL BODY WT (g) 269.8 253.9 269.9 267.8 BRAIN 1.84 2.04 1.94 1.85 ADRENALS 0.049 0.060 0.053 0.073 HEART 1.028 0.913 1.018 0.979 2F 26 27 28 29 30 265.1 226.0 244.5 235.2 243.0 1.88 1.81 1.86 1.89 1.86 0.066 0.066 0.063 0.051 0.085 1.067 0.908 1.023 0.899 0.960 KIDNEYS 1.53 1.41 1.70 1.82 1.70 1.57 1.86 1.70 1.61 LIVER 8.71 8.30 8.53 9.98 LUNGS & BR 1.125 1.142 1.236 1.177 9.09 7.23 8.81 8.41 9.15 1.171 1.037 1.118 1.074 1.090 Print No: 0026 Printed : 23-JUL-02 Xybion protocol number : MIN 313 MIN 313/023622 : 205 : APPENDIX 8 (Absolute organ weights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 GROUP 3F ANIMAL 31 32 33 34 35 TERMINAL BODY WT (g) 235.3 270.1 218.2 299.8 260.1 BRAIN 1.79 1.93 1.86 1.98 1.84 ADRENALS 0.069 0.076 0.057 0.061 0.071 HEART 1.032 0.946 0.843 0.952 0.943 4F 36 37 38 39 40 243.4 242.6 241.7 217.3 260.2 1.88 1.93 1.97 1.79 2.03 0.063 0.054 0.070 0.057 0.076 1.203 0.893 0.880 0.757 0.865 KIDNEYS 1.61 1.91 1.78 1.84 1.67 LIVER 8.90 10.00 8.61 11.96 9.82 LUNGS & BR 1.063 1.220 1.070 1.410 1.309 1.98 1.41 1.65 1.46 1.71 11.69 11.08 14.47 11.14 12.85 1.703 1.322 1.598 1.647 1.714 Print No: 0026 Printed: 23-JUL-02 Xybion protocol number: MIN 313 MIN 313/023622 : 206 : APPENDIX 8 (Absolute organ weights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 GROUP 1M ANIMAL 41 42 43 44 45 TERMINAL BODY WT (g) 466.6 506.1 496.4 493.2 450.3 BRAIN 2.17 2.09 1.97 2.13 2.21 ADRENALS 0.049 0.075 0.053 0.057 0.051 HEART 1.320 1.417 1.413 1.718 1.484 2M 46 47 48 49 50 498.8 409.2 485.8 423.7 470.8 2.23 1.99 2.13 2.17 2.14 0.045 0.047 0.050 0.054 0.065 1.405 1.685 1.481 1.254 1.417 KIDNEYS 2.76 2.75 2.78 2.91 2.80 LIVER 13.02 11.85 12.36 12.24 11.22 LUNGS & BR 1.398 1.599 1.519 1.389 1.455 2.98 2.75 3.34 2.73 3.06 14.24 11.50 13.44 10.70 12.50 1.549 1.422 1.487 1.406 1.470 Print No: 0028 Printed: 23-JUL-02 Xybion protocol number: MIN 313 MIN 313/023622 : 207 : APPENDIX 8 (Absolute organ weights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 GROUP 3M ANIMAL 51 52 53 54 55 TERMINAL BODY WT (g) 502.1 465.1 497.0 487.9 396.1 BRAIN 2.09 2.09 2.11 2.18 1.96 ADRENALS 0.049 0.050 0.053 0.058 0.048 HEART 1.568 1.596 1.378 1.677 1.348 4M 56 57 58 59 60 451.5 491.2 414.0 407.7 449.9 1.94 2.11 1.97 2.00 2.22 0.058 0.054 0.054 0.042 0.044 1.735 1.771 1.555 1.218 1.449 KIDNEYS 2.83 2.99 3.07 3.33 2.24 LIVER 13.72 14.91 14.63 15.37 11.05 LUNGS & BR 1.555 1.512 1.457 1.499 1.201 2.92 3.26 2.76 2.55 2.79 16.08 16.25 13.44 16.07 15.79 1.514 1.831 1.457 1.637 1.642 Print No: 0028 Printed: 23-JUL-02 Xybion protocol number: MIN 313 MIN 313/023622 : 208 : APPENDIX 8 (Absolute organ weights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 GROUP 1F ANIMAL 61 62 64 65 TERMINAL BODY WT (g) 313.0 285.2 270.2 297.2 BRAIN 2.05 1.94 1.94 1.95 ADRENALS 0.078 0.078 0.073 0.064 HEART 1.196 1.083 1.164 1.125 2F 66 67 68 69 70 304.1 316.9 258.3 286.4 291.7 2.17 2.01 1.95 2.12 2.01 0.065 0.078 0.055 0.072 0.083 0.864 1.223 0.908 1.136 1.020 KIDNEYS 1.86 1.92 1.75 1.97 1.83 2.27 1.77 1.78 1.84 LIVER 9.45 9.62 7.58 9.29 LUNGS & BR 1.365 1.276 1.206 1.314 8.35 9.64 7.93 8.97 9.12 1.242 1.279 1.128 UNSUITABLE 1.150 Print No: 0028 Printed : 23-JUL-02 Xybion protocol number : MIN 313 MIN 313/023622 : 209 : APPENDIX 8 (Absolute organ weights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 GROUP 3F ANIMAL 71 72 73 74 75 TERMINAL BODY WT (g) 260.4 251.6 276.7 251.5 249.9 BRAIN 1.89 1.88 2.00 1.85 2.00 ADRENALS 0.065 0.075 0.080 0.062 0.060 HEART 0.889 0.940 1.137 1.023 0.944 4F 76 77 78 79 80 232.2 250.8 259.0 297.6 265.0 1.90 1.87 2.03 1.94 1.94 0.055 0.057 0.063 0.071 0.071 0.849 0.988 0.918 0.950 0.918 KIDNEYS 1.66 1.73 1.96 1.73 1.76 LIVER 8.15 8.59 8.95 7.81 8.71 LUNGS & BR 1.187 1.132 1.079 1.046 1.003 1.43 1.75 1.53 1.74 1.88 8.63 9.02 9.49 11.37 10.40 1.082 1.142 1.259 1.242 1.212 Print No: 0028 Printed: 23-JUL-02 Xybion protocol number: MIN 313 MIN 313/023622 : 210 : APPENDIX 8 (Absolute organ weights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 0CONTROL 23 4 100-- POSF--- 30 300 GROUP 1M ANIMAL 81 82 83 84 85 TERMINAL BODY WT (g) 353.0 334.2 280.2 350.5 346.2 ADRENALS 0.076 0.045 0.037 0.054 0.051 BRAIN 21..1808 21..0719 1.91 HEART 1.510 1.214 0.933 1.408 1.353 KIDNEYS 2.42 2.41 1.91 2.47 2.41 LIVER 10.74 9.47 7.83 10.31 9.78 LUNGS & BR 1.424 1.126 1.005 1.379 1.319 4M 86 8887 89 90 333.4 325.3 281.2 335.2 314.4 0.063 0.059 0.040 0.061 0.057 1.98 21..0829 2.03 1.92 1.481 1.391 1.141 1.361 1.144 2.37 2.28 2.03 2.53 2.43 12.42 13.17 11.18 13.72 13.05 1.852 1.596 1.699 1.620 1.757 Print No: 0013 Printed: 23-JUL-02 Xybion protocol number: MIN 313A MIN 313/023622 : 211 : APPENDIX 8 (Absolute organ weights - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 0CONTROL 23 4 100-- POSF--- 30 300 GROUP 1F ANIMAL 91 92 93 94 95 TERMINAL BODY WT (g) 206.8 204.5 234.1 194.3 224.5 ADRENALS 0.061 0.053 0.084 0.061 0.072 BRAIN 1.84 1.80 1.78 1.81 1.98 HEART 0.795 0.923 1.061 0.850 0.914 KIDNEYS 1.62 1.41 1.49 11..6582 LIVER 6.72 6.76 7.19 7.10 8.24 LUNGS & BR 1.021 1.088 0.979 0.948 1.161 4F 96 97 98 10909 191.9 193.2 193.2 188.0 206.9 0.064 0.079 0.070 0.056 0.078 1.69 1.82 1.80 1.78 1.87 0.835 0.828 0.842 0.781 0.849 1.42 1.55 1.39 1.46 1.56 7.96 8.33 7.59 7.90 7.87 1.310 1.467 11..220816 1.407 Print No: 0013 Printed: 23-JUL-02 Xybion protocol number: MIN 313A APPENDIX 9 Individual pathological findings MIN 313/023622 bpTayhtehthomeloicsgtriuostds.cyoTpphaicethpdoialaotghgnoisolots,getyshrewepraeossructealtdrsrihoeedfreworuhetipcbrhyeswtewneortetphtaehtehcnoolnsosugebinsjsetsuc.steodTphtieoniioannirtsoiauoltfienbxeoatmphepienarathtrieoovlnoiegwwisatssb.uynadesretcaoknedn Study pathologist: Peer review: MPDaeotphravoreltonmgIei.sntP,teotefrPsaetnh-oJloongeys., B.V.M.S., M.R.C.V.S., DDSaiemrpeaucrtetolm.r eGon.ftPMoafcthCPoaoltrohmgoylioc,kg,y.M.V.B., M.R.C.V.S., PhD., F.R.C.Path., 212 : APPENDIX 9 Individual pathological findings Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0001 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH:: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 500.7 GRAMS MIN 313/023622 : 213 : NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -MEDIAN CLEFT PALE A R E A (S) ; ON E , SUBCAPSULAR, 1MM. LIVER : >NO SIGNIFICANT LESION STOMACH : -ANTRUM WHITE NODULE(S); RIDGE, 1MM. MUCOSA, ONE, NEAR TO LIMITING LUNGS & BRONCHI : -ALVEOLITIS,-MINIMAL -ALVEOLAR HAEMORRHAGE,-MINIMAL APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 MIN 313/023622 : 214 : GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0002 DATE OF DEATH:: 21-MAR-02 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH:: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 421.8 GRAMS NECROPSY PA THOL O GY OB SERVA T ION S HISTOPATHOLOGY HEART : -MYOCARDITIS, VENTRICULAR REGION,-MINIMAL, MULTI-FOCAL LN MANDIBULAR -ENLARGED; 10MM. -CONGESTED, MINIMAL LUNGS & BRONCHI : -ALVEOLAR HAEMORRHAGE,-MINIMAL APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 215 : ANIMAL NUMBER: 0003 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 457.3 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY HEART : -MYOCARDITIS, VENTRICULAR REGION,-MINIMAL, FOCAL KIDNEYS : -MINERALISATION, CORTICOMEDULLARY ,-MINIMAL LN MANDIBULAR : -CONGESTED LARYNX : -ARYTENOID - EPITHELIAL HYPERPLASIA,-MINIMAL LUNGS & BRONCHI : -AGGREGATIONS OF ALVEOLAR MACROPHAGES ,-MINIMAL APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 216 : ANIMAL NUMBER: 0004 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 433.8 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY HEART : -MYOCARDITIS, VENTRICULAR REGION,-MINIMAL, MULTI-FOCAL LUNGS & BRONCHI : -CONGESTED; A FEW AREAS, DIFFUSE KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-MINIMAL, FOCAL LUNGS & BRONCHI : -ALVEOLITIS,-MINIMAL MIN 313/023622 : 217 : APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0005 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 449.6 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY HEART : -MYOCARDITIS, VENTRICULAR REGION,-MINIMAL, FOCAL KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-MINIMAL, FOCAL LIVER : -PERIPORTAL LYMPHOCYTIC INFILTRATION,-MINIMAL LUNGS & BRONCHI : -AGGREGATIONS OF ALVEOLAR MACROPHAGES ,-MINIMAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 MIN 313/023622 : 218 : GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0041 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 466.6 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-MINIMAL, FOCAL -MEDULLARY MINERALISATION, -MINIMAL LUNGS & BRONCHI : -PERIVASCULAR INFLAMMATORY CELL INFILTRATION, -MINIMAL SKIN : -HAIRLOSS, MINIMAL; LEFT SIDE OF FACE , DIFFUSE. MIN 313/023622 : 219 : APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0042 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 506.1 GRAMS NECROPSY PA THOLO GY OB SERVA TION S HISTOPATHOLOGY KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-SLIGHT, FOCAL LUNGS & BRONCHI : -PERIVASCULAR INFLAMMATORY CELL INFILTRATION, -MINIMAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 ---POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 220 : ANIMAL NUMBER: 0043 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 496.4 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-MINIMAL, MULTI-FOCAL -CORTICAL LYMPHOCYTIC INFILTRATION,-SLIGHT, MULTI-FOCAL LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL -ALVEOLITIS,-MINIMAL -FOCAL OSSEOUS DEPOSITION,-MINIMAL SKIN : -HAIRLOSS, MINIMAL; RIGHT SIDE OF FACE, DIFFUSE. MIN 313/023622 : 221 : GROUP COMPOUND EXPOSURE LEVEL (PPM) : ANIMAL NUMBER: 0044 DATE OF DEATH: 19-APR- 02 APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 1234 Printed: 09-SEP-03 0 30 100 300 Protocol Number: MIN 313 SEX: MALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 493.2 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-MINIMAL, FOCAL -CORTICAL LYMPHOCYTIC INFILTRATION,-MINIMAL, MULTI-FOCAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** MIN 313/023622 : 222 : APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP COMPOUND EXPOSURE LEVEL (PPM) : 1 CONTROL 0 2 30 34 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0045 DATE OF DEATH: 19-APR- 02 SEX: MALE DOSE GROUP : 1 SACRIFICE STATUS: SCHEDULED, FIRST POST -RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 450.3 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -PELVIC DILATATION ,-SLIGHT *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 MIN 313/023622 : 223 : GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0006 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH:: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 509.2 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -MEDIAN CLEFT1 PALE A R E A (S) ; ON E , SUBCAPSULAR, 1MM. LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY,-SLIGHT -PARENCHYMAL INFLAMMATORY CELL INFILTRATION,-MINIMAL, FOCAL APPENDIX 9 (Individual pathological findings - continued) MIN 313/023622 : 224 : Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER:: 0007 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH:: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 403.3 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT LN MANDIBULAR -CONGESTED, MINIMAL APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0008 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 478.1 GRAMS MIN 313/023622 : 225 : NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT LUNGS & BRONCHI : -ALVEOLITIS,-MINIMAL MISCELLANEOUS : -ANIMAL THIN, MINIMAL PREPUTIAL GLANDS : -ABSCESS(ES); RIGHT, ONE, 3MM. PROSTATE : -ABSCESS(ES); RIGHT SIDE, ONE, 13X11X11MM. SKIN : -SCAB(S); GENITAL REGION, ONE, 3X2MM. APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 : 9ZZ GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER:: 0009 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 433.0 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT LN MANDIBULAR -ENLARGED ; UP TO 13MM. LUNGS & BRONCHI : -ALVEOLAR HAEMORRHAGE,-MINIMAL MIN 313/023622 APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0010 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 424.9 GRAMS MIN 313/023622 : 227 : NECROPSY PA THOLO GY OB SERVA TION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT -EXTRAMEDULLARY HAEMOPOEISIS,-MINIMAL LUNGS & BRONCHI : -CONGESTED, MINIMAL; PATCHY. LUNGS & BRONCHI : >NO SIGNIFICANT LESION SKIN : -HAIRLOSS, MINIMAL; SIDES OF FACE, DIFFUSE. MIN 313/023622 : 228 : APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP COMPOUND EXPOSURE LEVEL PPM): 1234 0 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0046 DATE OF DEATH: 19-APR- 02 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, FIRST POST -RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 498.8 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY SKIN : -HAIRLOSS, MINIMAL; SIDES OF FACE, DIFFUSE. *** ANIMAL HAS NO MICROSCOPIC FINDINGS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0047 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 409.2 GRAMS MIN 313/023622 : 229 : NECROPSY PA THOLO GY OB SERVA TION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE VACUOLATION,-SLIGHT STOMACH : -ANTRUM WHITE NODULE (S); MUCOSA, ONE, NEAR TO LIMITING RIDGE, 1MM. LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 MIN 313/023622 : 230 : GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0048 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 485.8 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY,-SLIGHT SKIN : -SCAB(S); RIGHT DORSAL LUMBAR REGION, ONE, 3X1MM. STOMACH : -ANTRUM WHITE NODULE (S); MUCOSA, ONE, NEAR TO LIMITING RIDGE, 1MM. MIN 313/023622 : 231 : APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0049 DATE OF DEATH: 19-APR- 02 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS:: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 423.7 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY,-MINIMAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 232 : ANIMAL NUMBER: 0050 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 470.8 GRAMS NECROPSY PA THOLO GY OB SERVA TION S HISTOPATHOLOGY LARYNX : -ARYTENOID - EPITHELIAL HYPERPLASIA,-MINIMAL -ARYTENOID - SUBEPITHELIAL INFLAMMATORY CELL INFILTRATION,MINIMAL LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY,-SLIGHT -EXTRAMEDULLARY HAEMOPOEISIS,-MINIMAL SKIN : -HAIRLOSS, MODERATE; LEFT AND RIGHT SCAPULAR REGIONS. APPENDIX 9 (Individual pathological findings - continued) MIN 313/023622 : 233 : Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0011 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS:: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH:: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 430.6 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE -CENTRILOBULAR HEPATOCYTE VACUOLATION, -MINIMAL MISCELLANEOUS -ANIMAL THIN, MINIMAL APPENDIX 9 (Individual pathological findings - continued) MIN 313/023622 : 234 : Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0012 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS:: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH:: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 465.0 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE -CENTRILOBULAR HEPATOCYTE VACUOLATION, -MINIMAL LN MANDIBULAR -CONGESTED, MINIMAL APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 235 : ANIMAL NUMBER: 0013 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 448.0 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE -CENTRILOBULAR HEPATOCYTE VACUOLATION, -MINIMAL SKIN : -HAIRLOSS, MINIMAL; REGION, DIFFUSE. SIDES OF FACE AND RIGHT DORSAL THORACIC APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 236 : ANIMAL NUMBER: 0014 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH:: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 401.6 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -MEDIAN CLEFT1 PALE A R E A (S) ; ON E , SUBCAPSULAR, 1MM. LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE -CENTRILOBULAR HEPATOCYTE VACUOLATION,-SLIGHT LUNGS & BRONCHI : -PROMINENT AGGREGATIONS OF LYMPHOCYTES,-MINIMAL -VASCULAR CONGESTION,-SLIGHT APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 237 : ANIMAL NUMBER: 0015 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 457.4 GRAMS NECROPSY PA THOLO GY OB SERVA TION S HISTOPATHOLOGY LARYNX : -ARYTENOID - SUBEPITHELIAL INFLAMMATORY CELL INFILTRATION,MINIMAL LUNGS & BRONCHI : -CONGESTED, MINIMAL LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE -EXTRAMEDULLARY HAEMOPOEISIS,-MINIMAL LUNGS & BRONCHI : -ALVEOLAR HAEMORRHAGE,-MARKED MIN 313/023622 : 238 : APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0051 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 502.1 GRAMS NECROPSY PA THOLO GY OB SERVA TION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY,-MINIMAL LUNGS & BRONCHI : -AGGREGATIONS OF ALVEOLAR MACROPHAGES ,-MINIMAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) MIN 313/023622 : 239 : Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0052 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 465.1 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY,-MINIMAL -EXTRAMEDULLARY HAEMOPOEISIS,-MINIMAL LN MANDIBULAR : -ENLARGED; RIGHT, ON E , 12MM. LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL -ALVEOLITIS,-MINIMAL STOMACH : -ANTRUM WHITE NODULE (S) ; MUCOSA, ONE, NEAR TO LIMITING RIDGE, PUNCTATE. MIN 313/023622 : 240 : APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0053 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 497.0 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT -PERIPORTAL LYMPHOCYTIC INFILTRATION,-MINIMAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** MIN 313/023622 : 241 : APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0054 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 487.9 GRAMS NECROPSY PA THOLO GY OB SERVA TION S HISTOPATHOLOGY LARYNX : -ARYTENOID - EPITHELIAL HYPERPLASIA,-MINIMAL LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) MIN 313/023622 : 242 : Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0055 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 3 SACRIFICE STATUS:: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 396.1 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY EPIDIDYMIDES : -SWELLING(S) ; RIGHT CAUDA, ONE, 3MM. LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY,-MINIMAL MIN 313/023622 : 243 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0016 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 377.6 GRAMS NECROPSY PA THOLO GY OB SERVA TION S HISTOPATHOLOGY LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MODERATE TRACHEA : -EPITHELIAL HYPERPLASIA,-MINIMAL, FOCAL -EPITHELIAL INFLAMMATORY CELL INFILTRATION,-MINIMAL, FOCAL -SUBEPITHELIAL INFLAMMATORY AGGREGATIONS ,-MINIMAL , FOCAL -SUBEPITHELIAL FIBROBLAST PROLIFERATION,-MINIMAL, FOCAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0017 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 332.9 GRAMS MIN 313/023622 : 244 : NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT -ARYTENOID - EPITHELIAL HYPERPLASIA,-MINIMAL LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-SLIGHT -ALVEOLITIS,-MINIMAL MISCELLANEOUS : -ANIMAL THIN STOMACH : -CORPUS WHITE NODULE (S) ; MUCOSA, ONE NEAR TO LIMITING RIDGE, 1MM. APPENDIX 9 (Individual pathological findings - continued) MIN 313/023622 : 245 : Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0018 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH : 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 385.0 GRAMS NECROPSY PA THOL O GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -FOCAL CAPSULAR CONGESTION,-MINIMAL LIVER : -ENLARGED; 19.38G. LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE LN MANDIBULAR : -CONGESTED, MODERATE LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL MISCELLANEOUS : -ANIMAL THIN APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0019 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 403.3 GRAMS MIN 313/023622 : 246 : NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-MINIMAL, FOCAL LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT LIVER : -MEDIAN CLEFT PALE AREA (S) ; ONE, SUBCAPSULAR, 2MM -ENLARGED; 20.97G. LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE LN MANDIBULAR : -CONGESTED, MINIMAL LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL -ALVEOLAR HAEMORRHAGE,-MINIMAL MISCELLANEOUS : -ANIMAL THIN, MINIMAL APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0020 DATE OF DEATH: 21-MAR-02 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 358.4 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY MIN 313/023622 : 247 : LIVER : -ENLARGED; 18.03G LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT -ARYTENOID - EPITHELIAL HYPERPLASIA,-MINIMAL -ARYTENOID - SUBEPITHELIAL INFLAMMATORY CELL INFILTRATION,MINIMAL LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE -FOCAL/MULTIFOCAL SINGLE CELL NECROSIS INFLAMMATORY CELL INFILTRATION,-MINIMAL LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL -ALVEOLAR HAEMORRHAGE,-MINIMAL STOMACH : -ANTRUM WHITE NODULE (S); MUCOSA, ONE, NEAR TO LIMITING RIDGE, 1MM. TRACHEA : -EPITHELIAL HYPERPLASIA,-MINIMAL, FOCAL MIN 313/023622 : 248 : APPENDIX 9 (Individual pathological findings - continued) Print No: 0034 GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 ---POSF--- 30 100 300 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0056 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 451.5 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-MINIMAL, FOCAL LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT -ARYTENOID - EPITHELIAL HYPERPLASIA,-SLIGHT -ARYTENOID - EPITHELIAL HYPERKERATOSIS PARAKERATOSIS,-MINIMAL -VENTROLATERAL EPITHELIAL SQUAMOUS METAPLASIA, -MINIMAL -VENTRAL POUCH - EPITHELIAL HYPERPLASIA,-MINIMAL -VENTRAL POUCH - INFLAMMATORY CELL INFILTRATION, -MINIMAL LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT -CENTRILOBULAR HEPATOCYTE NECROSIS/INFLAMMATORY CELL INFILTRATION/SINUSOIDAL CONGESTION,-MODERATE, MULTI-FOCAL LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL -FOCAL OSSEOUS DEPOSITION,-MINIMAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0057 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 491.2 GRAMS MIN 313/023622 : 249 : NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-MINIMAL, MULTI-FOCAL -MEDULLARY TUBULAR BASOPHILIA, -MINIMAL, FOCAL -MEDULLARY TUBULAR FIBROSIS,-MINIMAL, FOCAL LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-SLIGHT SKIN : -HAIRLOSS, MODERATE; RIGHT CRANIAL REGION. APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0058 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 414.0 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY MIN 313/023622 : 250 : KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-SLIGHT, MULTI-FOCAL -MEDULLARY MINERALISATION, -MINIMAL LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT -ARYTENOID - EPITHELIAL HYPERPLASIA,-SLIGHT -ARYTENOID - EPITHELIAL HYPERKERATOSIS PARAKERATOSIS,-MINIMAL -VENTROLATERAL EPITHELIAL HYPERPLASIA,-MINIMAL -VENTRAL POUCH - EPITHELIAL HYPERPLASIA,-MINIMAL -VENTRAL POUCH - INFLAMMATORY CELL INFILTRATION, -MINIMAL LIVER : -MEDIAN CLEFT PALE A R E A (S); ONE, SUBCAPSULAR, 2MM. LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT -HEPATOCYTE VACUOLATION, MEDIAN CLEFT,-SLIGHT LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-SLIGHT -PERIVASCULAR INFLAMMATORY CELL INFILTRATION, -MINIMAL SKIN : -HAIRLOSS, MINIMAL; REGION. RIGHT SCAPULAR REGION AND CRANIAL APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0059 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 407.7 GRAMS MIN 313/023622 : 251 : NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT LIVER : -LOBULAR PATTERN ACCENTUATED, MINIMAL LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT -CENTRILOBULAR INFLAMMATORY CELL INFILTRATION,-MINIMAL, FOCAL LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-SLIGHT SKIN : -HAIRLOSS, MODERATE; CRANIAL REGION, RIGHT SIDE OF FACE AND RIGHT SCAPULAR REGION, DIFFUSE. TRACHEA : -SUBEPITHELIAL INFLAMMATORY AGGREGATIONS,-SLIGHT APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0060 DATE OF DEATH: 19-APR-02 SEX: MALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 449. 9 GRAMS MIN 313/023622 : 252 : NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY MISCELLANEOUS : -ANIMAL THIN, MINIMAL SKIN : -HAIRLOSS, MINIMAL; FORELIMBS. LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT LUNGS & BRONCHI : -FOCAL BRONCHOALVEOLAR HYPERPLASIA,-MINIMAL -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL MIN 313/023622 : 253 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0021 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 269.8 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -CORTICAL LYMPHOCYTIC INFILTRATION,-MINIMAL, FOCAL LARYNX : -ARYTENOID - EPITHELIAL HYPERPLASIA,-MINIMAL LIVER : -PERIPORTAL LYMPHOCYTIC INFILTRATION,-SLIGHT *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** MIN 313/023622 : 254 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0022 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP : 1 SACRIFICE STATUS SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH : 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 253.9 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY MISCELLANEOUS : -FUR STAINING; DORSUM BROWN. *** ANIMAL HAS NO MICROSCOPIC FINDINGS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0023 DATE OF DEATH: 20-MAR-02 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: UNSCHEDULED (F) STUDY DAY OF DEATH: 91 STUDY WEEK OF DEATH: 13 TERMINAL BODY WEIGHT: 242.4 GRAMS MIN 313/023622 : 255 : NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -MEDIAN CLEFT PALE AREA (S) ; ONE , SUBCAPSULAR, 2MM. LUNGS & BRONCHI : -CONGESTED, SEVERE -INCOMPLETE COLLAPSE SKIN : -HAIRLOSS, MINIMAL; VENTRAL SURFACE, PATCHY, DIFFUSE. UTERUS : -FLUID DISTENSION, MINIMAL KIDNEYS : -MEDULLARY MINERALISATION, -MINIMAL LIVER : -PARENCHYMAL INFLAMMATORY CELL INFILTRATION,-MINIMAL, FOCAL -HEPATOCYTE VACUOLATION, MEDIAN CLEFT,-MINIMAL LUNGS & BRONCHI : -ALVEOLAR HAEMORRHAGE,-MARKED -VASCULAR CONGESTION, -MODERATE -EARLY AUTOLYSIS,-PRESENT UTERUS : -LUMINAL DILATATION, -MINIMAL MIN 313/023622 : 256 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0024 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 269.9 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-SLIGHT, FOCAL -CORTICAL INTERSTITIAL FIBROBLAST PROLIFERATION/ FIBROSIS,SLIGHT, FOCAL LIVER : -EXTRAMEDULLARY HAEMOPOEISIS,-MINIMAL LUNGS & BRONCHI : -AGGREGATIONS OF ALVEOLAR MACROPHAGES ,-SLIGHT -ALVEOLAR HAEMORRHAGE,-MINIMAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i 0CONTROL 23 4 100---POSF--- 30 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 257 : ANIMAL NUMBER: 0025 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS:: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT': 267.8 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -CORTICAL TUBULAR BASOPHILIA, -MINIMAL, FOCAL SKIN : -HAIRLOSS, MINIMAL; VENTRAL SURFACE AND RIGHT HINDLIMB, DIFFUSE. APPENDIX 9 (Individual pathological findings - continued) MIN 313/023622 : 258 : GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0061 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 313.0 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY SKIN : -HAIRLOSS, MINIMAL; REGION, DIFFUSE. RIGHT SCAPULAR AND RIGHT DORSAL THORACIC LUNGS & BRONCHI -AGGREGATIONS OF ALVEOLAR MACROPHAGES ,-MINIMAL -PERIVASCULAR INFLAMMATORY CELL INFILTRATION, -MINIMAL APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 259 : ANIMAL NUMBER: 0062 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS : SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 285.2 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -MINERALISATION, CORTICOMEDULLARY,-MINIMAL SKIN : -HAIRLOSS, MINIMAL; DORSAL THORACIC REGION, DIFFUSE MIN 313/023622 : 260 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0063 DATE OF DEATH: 03-JAN-02 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: UNSCHEDULED (H) STUDY DAY OF DEATH: 15 STUDY WEEK OF DEATH: 3 TERMINAL BODY WEIGHT: 213.3 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-MINIMAL, FOCAL -CORTICAL INTERSTITIAL FIBROBLAST PROLIFERATION/ FIBROSIS,MINIMAL, FOCAL -MEDULLARY MINERALISATION, -MINIMAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 261 : ANIMAL NUMBER: 0064 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 270.2 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -PERIPORTAL LYMPHOCYTIC INFILTRATION,-MINIMAL LN MANDIBULAR : -ENLARGED; 9MM. LUNGS & BRONCHI : -AGGREGATIONS OF ALVEOLAR MACROPHAGES ,-MINIMAL -ALVEOLAR HAEMORRHAGE,-SLIGHT APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 : Z9Z ANIMAL NUMBER: 0065 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 297.2 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -MINERALISATION, CORTICOMEDULLARY ,-MINIMAL -MEDULLARY MINERALISATION, -MINIMAL LIVER : -EXTRAMEDULLARY HAEMOPOEISIS,-MINIMAL SKIN : -HAIRLOSS, MINIMAL; FORELIMBS, DIFFUSE. MIN 313/023622 APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 263 : ANIMAL NUMBER: 0026 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 265.1 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -PELVIC DILATION, MINIMAL; RIGHT. LUNGS & BRONCHI : -FOCAL OSSEOUS DEPOSITION,-MINIMAL MIN 313/023622 : 264 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0027 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 226.0 GRAMS NECROPSY PA THOLO GY SKIN : -HAIRLOSS, MINIMAL; DORSAL THORACIC REGION, DIFFUSE. OB SERVA TION S HISTOPATHOLOGY UTERUS : -FLUID DISTENSION, MODERATE *** ANIMAL HAS NO MICROSCOPIC FINDINGS RECORDED *** MIN 313/023622 : 265 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0028 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 244.5 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY UTERUS : -FLUID DISTENSION, MODERATE *** ANIMAL HAS NO MICROSCOPIC FINDINGS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) MIN 313/023622 : 266 : GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0029 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 235.2 GRAMS NECROPSY PA THOLO GY OB SE RVA T ION S HISTOPATHOLOGY LN MANDIBULAR -ENLARGED ; ONE, 12MM. LUNGS & BRONCHI -AGGREGATIONS OF ALVEOLAR MACROPHAGES ,-MINIMAL -PERIVASCULAR INFLAMMATORY CELL INFILTRATION, -MINIMAL APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0030 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 243.0 GRAMS MIN 313/023622 : 267 : NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LARYNX : -VENTRAL POUCH - EPITHELIAL HYPERPLASIA,-MINIMAL LIVER : -PERIPORTAL LYMPHOCYTIC INFILTRATION,-MINIMAL STOMACH : -ANTRUM WHITE NODULE (S); MUCOSA, ONE, NEAR TO LIMITING RIDGE, 1MM. THYMUS : -DARK UTERUS : -FLUID DISTENSION, MINIMAL APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0066 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 304.1 GRAMS MIN 313/023622 : 268 : *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** *** ANIMAL HAS NO MICROSCOPIC FINDINGS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 269 : ANIMAL NUMBER: 0067 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 316.9 GRAMS NECROPSY PA THOLO GY OB SE RV A T ION S HISTOPATHOLOGY KIDNEYS : -PELVIC DILATION, MODERATE ; RIGHT. LARYNX : -VENTRAL POUCH - FORIGN BODY IN LUMEN, RELATED TO EPITHELIAL HYPERPLASIA/ INFLAMMATORY CELL INFILTRATION,-SLIGHT URETERS : -DISTENDED; RIGHT, 1MM. APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 270 : ANIMAL NUMBER: 0068 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 258.3 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL SKIN : -HAIRLOSS, MINIMAL; RIGHT, DIFFUSE. UTERUS : -FLUID DISTENSION, MODERATE MIN 313/023622 : 271 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0069 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 2 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 286.4 GRAMS NECROPSY PA THOLO GY SKIN : -HAIRLOSS, MINIMAL; RIGHT SIDE IF FACE, DIFFUSE. OB SERVA TION S HISTOPATHOLOGY UTERUS : -FLUID DISTENSION, MODERATE *** ANIMAL HAS NO MICROSCOPIC FINDINGS RECORDED *** MIN 313/023622 : 272 : APPENDIX 9 (Individual pathological findings - continued) GROUP COMPOUND EXPOSURE LEVEL (PPM) : 1 CONTROL 0 2 30 34 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0070 DATE OF DEATH: 19-APR--02 SEX: FEMALE DOSE GROUP : 2 SACRIFICE STATUS SCHEDULED, FIRST POST -RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 291.7 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LN MANDIBULAR -ENLARGED; 9MM. *** ANIMAL HAS NO MICROSCOPIC FINDINGS RECORDED *** MIN 313/023622 : 273 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0031 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 235.3 GRAMS NECROPSY PA THOL O GY OB SERVA T ION S HISTOPATHOLOGY LN MANDIBULAR -ENLARGED ; UP TO 10MM. *** ANIMAL HAS NO MICROSCOPIC FINDINGS RECORDED *** MIN 313/023622 : 274 : APPENDIX 9 (Individual pathological findings - continued) GROUP COMPOUND EXPOSURE LEVEL (PPM) : 1 CONTROL 0 2 30 34 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0032 DATE OF DEATH: 21-MAR- 02 SEX: FEMALE DOSE GROUP : 3 SACRIFICE STATUS SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH : 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 270.1 GRAMS NECROPSY PA THOL O GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -PERIPORTAL HEPATOCYTE VACUOLATION, -MINIMAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0033 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 218.2 GRAMS MIN 313/023622 : 275 : NECROPSY PA THOLO GY OB SE RVA T ION S HISTOPATHOLOGY LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL SKIN : -HAIRLOSS, MINIMAL; INTER-ORBITAL REGION, DIFFUSE. TAIL : -SWELLING(S) ; ONE,, 3X2X2MM, (TAKEN WITH TATTOO). UTERUS : -FLUID DISTENSION, MODERATE MIN 313/023622 : 276 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0034 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 299.8 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY STOMACH : -ANTRUM WHITE NODULE (S) ; MUCOSA, TWO, NEAR TO LIMITING RIDGE, PUNCTATE. *** ANIMAL HAS NO MICROSCOPIC FINDINGS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) MIN 313/023622 : 277 : GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0035 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH:: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 260.1 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY MISCELLANEOUS -ANIMAL THIN, MINIMAL LARYNX : -VENTRAL POUCH - EPITHELIAL HYPERPLASIA,-MINIMAL LUNGS & BRONCHI : -AGGREGATIONS OF ALVEOLAR MACROPHAGES ,-MINIMAL APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 278 : ANIMAL NUMBER: 0071 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 260.4 GRAMS NECROPSY PA THOLO GY OB SERVA TION S HISTOPATHOLOGY LARYNX : -VENTRAL POUCH - FORIGN BODY IN LUMEN, RELATED TO EPITHELIAL HYPERPLASIA/ INFLAMMATORY CELL INFILTRATION,-MODERATE LIVER : -MEDIAN CLEFT PALE AREA (S) ; ONE , SUBCAPSULAR. LIVER : >NO SIGNIFICANT LESION STOMACH : -ANTRUM WHITE NODULE (S) ; MUCOSA, TWO, NEAR TO LIMTING RIDGE PUNCTATE. MIN 313/023622 : 279 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0072 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 251.6 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -PARENCHYMAL INFLAMMATORY CELL INFILTRATION,-MINIMAL, FOCAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** MIN 313/023622 : 280 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0073 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, FIRST POST -RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 276.7 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY STOMACH : -ANTRUM WHITE NODULE (S) ; MUCOSA, THREE, NEAR TO LIMITING RIDGE, 1MM. UTERUS : -FLUID DISTENSION, MINIMAL *** ANIMAL HAS NO MICROSCOPIC FINDINGS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 281 : ANIMAL NUMBER: 0074 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 251.5 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LUNGS & BRONCHI : -ALVEOLAR HAEMORRHAGE,-MINIMAL UTERUS : -FLUID DISTENSION, MODERATE MIN 313/023622 : 282 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0075 DATE OF DEATH: 19-APR- 02 SEX: FEMALE DOSE GROUP: 3 SACRIFICE STATUS:: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 249.9 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY SKIN : -HAIRLOSS, MINIMAL; LEFT DORSUM, DIFFUSE. *** ANIMAL HAS NO MICROSCOPIC FINDINGS RECORDED *** APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 2 30 34 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0036 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 243.4 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY MIN 313/023622 : 283 : KIDNEYS : -PELVIC DILATION, MINIMAL; RIGHT. KIDNEYS : -CORTICAL TUBULAR BASOPHILIA,-MINIMAL, FOCAL -UROTHELIAL HYPERPLASIA, UNILATERAL,-MINIMAL, FOCAL -PELVIC DILATATION, -MODERATE LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT -ARYTENOID - EPITHELIAL HYPERPLASIA,-MINIMAL, FOCAL LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT LN MANDIBULAR : -ENLARGED; 9MM. -CONGESTED; RIGHT, ONE. LUNGS & BRONCHI : -INCOMPLETE COLLAPSE, MINIMAL LUNGS & BRONCHI : -FOCAL OSSEOUS DEPOSITION,-MINIMAL SKIN : -HAIRLOSS, MINIMAL; RIGHT FORELIMB, DIFFUSE. APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0037 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH : 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 242.6 GRAMS MIN 313/023622 : 284 : NECROPSY PA THOLO GY OB SERVA TION S HISTOPATHOLOGY LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL MISCELLANEOUS : -ANIMAL THIN, MINIMAL -FUR BADLY GROOMED, MINIMAL TAIL : -SWELLING(S); ON E ,, FIRM, 3X1MM. UTERUS : -FLUID DISTENSION, MODERATE APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0038 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 241.7 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY MIN 313/023622 : 285 : LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT -ARYTENOID - EPITHELIAL HYPERPLASIA,-MINIMAL, FOCAL LIVER : -ENLARGED; 14.47G. LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE -PROMINENT CENTRILOBULAR HEPATOCYTE PIGMENT,-MINIMAL LUNGS & BRONCHI : -INCOMPLETE COLLAPSE, MINIMAL LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-SLIGHT -ALVEOLAR HAEMORRHAGE,-MINIMAL -FOCAL OSSEOUS DEPOSITION,-MINIMAL MISCELLANEOUS : -ANIMAL THIN SKIN : -HAIRLOSS, MINIMAL; DIFFUSE. HINDLIMBS AND LEFT CERVICAL REGION, APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 -- POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0039 DATE OF DEATH: 21-MAR-02 SEX : FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH: 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 217.3 GRAMS NECROPSY PA THOLO GY OB SERVA TION S HISTOPATHOLOGY LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT MIN 313/023622 : 286 : LIVER : -MEDIAN CLEFT PALE A R E A (S); ONE, SUBCAPSULAR, 3MM. LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA, -MODERATE -HEPATOCYTE VACUOLATION, MEDIAN CLEFT,-MINIMAL LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-SLIGHT MISCELLANEOUS : -ANIMAL THIN SKIN : -HAIRLOSS, MODERATE; LEFT HINDLIMB. STOMACH : -FORESTOMACH DEPRESSION(S); EPITHELIAL ASPECT,, ONE, CRATERLIKE, 1MM, IN OESOPHAGEAL GROOVE. UTERUS : -FLUID DISTENSION, MODERATE APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i 0CONTROL 23 4 100-- POSF--- 30 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 287 : ANIMAL NUMBER: 0040 DATE OF DEATH: 21-MAR-02 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE STUDY DAY OF DEATH : 92 STUDY WEEK OF DEATH: 14 TERMINAL BODY WEIGHT: 260.2 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT LIVER : -ENLARGED; 12.85G. LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY EXTENDING INTO MIDZONAL AREA,-SLIGHT LUNGS & BRONCHI : -INCOMPLETE COLLAPSE, MINIMAL; RIGHT. -DARK A R E A (S); RIGHT, MIDDLE LOBE, ON E , SUBPLEURAL, 3MM. LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL -ALVEOLAR HAEMORRHAGE,-MINIMAL -PERIVASCULAR INFLAMMATORY CELL INFILTRATION, -MINIMAL -FOCAL OSSEOUS DEPOSITION,-MINIMAL APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 2 30 34 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 288 : ANIMAL NUMBER: 0076 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 232.2 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY KIDNEYS : -MINERALISATION, CORTICOMEDULLARY ,-MINIMAL LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY,-MINIMAL -PROMINENT CENTRILOBULAR HEPATOCYTE PIGMENT,-MINIMAL -EXTRAMEDULLARY HAEMOPOEISIS,-MINIMAL LN MANDIBULAR : -CONGESTED APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0077 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 250.8 GRAMS MIN 313/023622 : 289 : NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT -ARYTENOID - SUBEPITHELIAL INFLAMMATORY CELL INFILTRATION,MINIMAL, FOCAL -PROMINENT DILATED ACINI VENTRAL GLAND,-PRESENT LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY,-MINIMAL -PROMINENT CENTRILOBULAR HEPATOCYTE PIGMENT,-MINIMAL LN MANDIBULAR : -CONGESTED LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL -AGGREGATIONS OF ALVEOLAR MACROPHAGES ,-MINIMAL APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): i CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 MIN 313/023622 : 290 : ANIMAL NUMBER: 0078 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 259.0 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT LUNGS & BRONCHI : -AGGREGATIONS OF ALVEOLAR MACROPHAGES ,-MINIMAL -FOCAL OSSEOUS DEPOSITION,-MINIMAL UTERUS : -FLUID DISTENSION, MODERATE MIN 313/023622 : 291 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 CONTROL 0 234 ---POSF--- 30 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 007 9 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 297.6 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LARYNX : -NECROSIS OF VENTRAL CARTILAGE,-PRESENT LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY,-MINIMAL LUNGS & BRONCHI : -FOAMY ALVEOLAR MACROPHAGES/SEPTAL THICKENING/ SCATTERED ALVEOLAR MACROPHAGES,-MINIMAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** MIN 313/023622 : 292 : APPENDIX 9 (Individual pathological findings - continued) GROUP : COMPOUND : EXPOSURE LEVEL(PPM): 1 0CONTROL 2 30 34 100 300 Print No: 0034 Printed: 09-SEP-03 Protocol Number: MIN 313 ANIMAL NUMBER: 0080 DATE OF DEATH: 19-APR-02 SEX: FEMALE DOSE GROUP: 4 SACRIFICE STATUS: SCHEDULED, FIRST POST-RECOV SAC STUDY DAY OF DEATH: 121 STUDY WEEK OF DEATH: 18 TERMINAL BODY WEIGHT: 265.0 GRAMS NECROPSY PA THOLO GY OB SERVA T ION S HISTOPATHOLOGY LIVER : -CENTRILOBULAR HEPATOCYTE HYPERTROPHY,-MINIMAL LUNGS & BRONCHI : -PERIVASCULAR INFLAMMATORY CELL INFILTRATION, -MINIMAL -FOCAL OSSEOUS DEPOSITION,-MINIMAL *** ANIMAL HAS NO GROSS OBSERVATIONS RECORDED *** APPENDIX 10 pH values for terminal urine - individual values MIN 313/023622 Group : 1 Compound : Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 MaiGnrsotuupdy animals Males Animal number PH Females Animal number PH 1 21 34 5 8-.0 7.5 7.8 2212 2234 25 78.-.32 7-.7 2 6 8.4 26 7.8 7 8.0 27 7.9 8 9 7.6 8.4 28 29 8-.0 3 10 1112 7.4 7-.7 30 3312 7-.7 - 1134 15 8-.0 8.4 3334 35 76..27a 7.3 4 1167 1189 20 8.-1 8.1 3367 3389 40 8.-1 8.4 88..02 Sample taken from bladder at necropsy Sample volume < 8 ^l required to obtain accurate pH reading/No sample : 293 : APPENDIX 10 (pH values for terminal urine - continued) MIN 313/023622 Group : 1 Compound : Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 Recovery study^animals Group Males nAunmimbearl pH Females Animal pH number 1 41 42 6.6 6612 7-.5 4434 7-.8 6634 De-ad 45 6.2 65 - 2 46 7.8 66 - 47 - 67 7.6 48 - 68 - 49 - 69 - 50 8.8 70 - 3 51 52 7.3 7.9 7712 -- 5534 7-.5 73 74 6.3 55 7.2 75 7.8 4 5567 -- 7767 -- 5589 6-.6 7789 -- 60 - 80 - - Ssaammppllee volume < 8 ^l required to obtain accurate pH reading/No Animal 63 - unscheduled sacrifice : 294 : APPENDIX 10 (pH values for terminal urine - continued) MIN 313/023622 Group : 1 Compound : Control Exposure level (ppm) : 0 2 -- PO3SF-- 4 30 100 300 Satellite animals Group Males nAunmimbearl pH Females Animal number pH 1 4 8812a 7.-1 8834a 85 7-.5 - 86 6.4 9912 9934 95 96 7-.6 6.0 6.5 6.1 87 7.7 97 5.9 88 6.0 98 6.3 9809 7.-1 19090 6-.0 Sample volume < 8 ^l required to obtain accurate pH reading Sample pH'd approximately 1.5 hours following sample collection due to failure of pH hardware : 295 : APPENDIX 11 Cell proliferation findings MIN 313/023622 : 296 : GCExorpomuoppsuourendlevel (ppm) ::: Con01trol 2 30 -- P1O30S0F-- 4 300 Satellite animals Group 1M 4M 1F 4F CeAll nNp19999999999888888888i0ro113m30245678952467890o. lailferaPtioos63347423244366344451ni11111304606759545205tiinvedexN(%e99999999999999999999gL87756646653565433565pa31555506940499967809toeivsvieetliv1eT11111111111111111111co00000000000000000000et00000000000000000000la00000000000000000000lls) C.633474232443651P................111155046067945I.* 63444.....13520 Pos42246633364345555555i11064740640675557490tive Ne999999999999999g445667734666445La133304660469604teivveel 999994545455509 2T11111111111111111111o00000000000000000000t00000000000000000000a00000000000000000000l C.42246633364345555555P....................1.1555064740640677490I.* Pos33274323433643458555i13331334987962668596tive Ne999999999999999g456766721656464aL111376779248744tievveel 999995354659472 3T11111111111111111111o00000000000000000000t00000000000000000000a00000000000000000000l C.33274323433643458555P.....................11333335498796266896I.* Group MMeaanle(c%ellpporsoitliivfeercaetlilosn)Fienmdeaxle 41 44..04 44..88 APPENDIX 11 (Cell proliferation findings - continued) GCExorpomuoppsuourendlevel (ppm) ::: Con01trol 2 30 -- P1O30S0F-- 4 300 MIN 313/023622 : 297 : Main group animals Group 1M 4M 1F 4F CeAll nNp222222333341111i23451ro13m0245678906789o. lailferaPtiooNNNNNNNNNNNNNNNNNNNNsniRRRRRRRRRRRRRRRRRRRRtiinvedexN(%egNNNNNNNNNNNNNNNNNNNNLpaRRRRRRRRRRRRRRRRRRRRtoeivsvieetliv1eTNNNNNNNNNNNNNNNNNNNNcoeRRRRRRRRRRRRRRRRRRRRtlalls) C.NNNNNNNNNNNNNNNNNNNNPRRRRRRRRRRRRRRRRRRRR.I.* PoNNNNNNNNNNNNNNNNNNNNsiRRRRRRRRRRRRRRRRRRRRtive NegNNNNNNNNNNNNNNNNNNNNLaRRRRRRRRRRRRRRRRRRRRteivveel 2TNNNNNNNNNNNNNNNNNNNNoRRRRRRRRRRRRRRRRRRRRtal C.NNNNNNNNNNNNNNNNNNNNPRRRRRRRRRRRRRRRRRRRR.I.* PoNNNNNNNNNNNNNNNNNNNNsiRRRRRRRRRRRRRRRRRRRRtive NegNNNNNNNNNNNNNNNNNNNNaRRRRRRRRRRRRRRRRRRRRLtievveel 3TNNNNNNNNNNNNNNNNNNNNoRRRRRRRRRRRRRRRRRRRRtal C.NNNNNNNNNNNNNNNNNNNNPRRRRRRRRRRRRRRRRRRRR.I.* Group MMeaanle(c%ellpporsoitliivfeercaetlilosn)Fienmdeaxle 41 NNRR NNRR NR Not recorded MIN 313/023622 ADMINISTRATION OF POSF BY INHALATION TO RATS : 298 : ASiumthonorMoore CONTENTS MIN 313/023622 Page TEST SUBSTANCE AND ADMINISTRATION AEPETTTCTrxxaeeehdorsssppamgctttoomeeAAsisstnbduuuttiecbummrrseerosrtooentrMccaass.chh.nppt.oeia.ahhc.nonm.meee.tni..rrrtb..b.oaee....e..ert...raiG.i..r.on..n.s..c.en.g...a.o...n.s...l..ns....ye.....y.d....r.s.....s.a.i..i....tt..s.t...ei....i...o...mo..........n.....n..........s..................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................333333333000000000115534002 RESULTS NVDCCohaiaslampccmouuiunlbsarasetlicriooocTnnon.esnc...mec....ne..p..nt..e.r.t..ar.r...ata..i..tto..ui..on..r...n..e..........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................333330000067677 FIGURES AB.. SScchheemmaattiicc ooff aa rFooduernietrinThraalnastifoonrmdoIsnifnrgarseydstSepmec..t.r..o..p..h..o..t.o..m....e..t.e..r..a..n..d...t.h..e....s.a..m...p..l..i.n..g...s..y..s.t..e.m....330089 TABLES ABDC.... NCOChhopaamemmrianbbtiaeenlrrgctceocomnoncncpedeeninrttaitrortaaunttrisioeonon-sfsetoxhofpefPoPiOsnOuhSSraeFFla(mpt(ippeopamnnm)ev)x-ap-ilnodudsaeuiisvlr.yie..d.m.su.y.ae.s.la.t.nae..nm.v.d.a....m.l...u..e..e..a..s..n.........e......x......p......o........s....u......r.....e.........v.......a......l...u........e.......s...............................................................333321111003 APPENDICES AB.. IMndeitvhioddusaol fPsOaSmFplceoncoclelnetcrtaiotinonanmdeaansaulryesmisefnotrs.P..O...S...F........................................................................................................................333222 : 299 : TEST SUBSTANCE AND ADMINISTRATION MIN 313/023622 TEST SUBSTANCE The test substance, POSF, is a liquid with boiling point of 154C. Au1n4tciJolunintsewigan2s0mt0re1an.ntsTofehfretrhetedesTttoesstuhtbeAsartattimnccloeesp(w4haexsre2s0gtoekrneged,raLsteiooctnunrsueymlystbeiemnr.t0h4e02o2ri7g)i,nwalacsornetcaeiinveerds fartormootmhetSempopnesroartuorne Idsntuafrboairtlmiiotyantioooffnthupesretoevosintdsetuhdbesbtsyatuntdcheye.isSTtphhoeenrsesotsraptoeinnddspiicbuairltiiettydy wothfaatsthe>th9Se5p.ot5en%ssto.rs.uIbnsfotarnmcaetiwonasresgtaabrdleingforthtehepuirnitteyndanedd ADMINISTRATION bTehleowte:st material was administered to the rats using snout-only exposure chambers, as described Tgradacrehtihnsevi,eeercrbvashyetoadinmritnbotbhhyetarrholmaeuategitcomthhenarowimsnfphrgbohiecmetrhhreaedsirnwr.tieoeasudstt aspoiurrnoblwdsytuaacesnexcpdpeaosbsssyuueprdemplaeycttheauarmsifnilnboggewrtshpr.eoaltyelTipqhorueofipd2tya9tlreeglsn/etmet sicnsuyhubartsiemtnagfbnoeecrsreamcidnoomtnoucinneatinesttdgrralaaottisinoosnnsvsytaorwpinoteghureeer DpiarnanritieafetlfilsiaeymlrisneiissnnoeatortrdtcfyieoncrngghtcesaoenmnemrertbraaqeatiurintoiitoarnaetnimdtnsriotoathsolfepsPhwcoOehbiratStehamFiosnbuawemttreahprcneeloiemnspta)cra.reolgsndMetuprtacrientecisodohernanbmatycd(lbobjteuhsarseestemtcsodoeelntoneacntcrsegttniewhotter.nearFtoeioofmundrsaiifedfwreeTreteorrneattnhdsseyfeortteeirnmsrmgt emIinnfafeetrdeeardriedardulartd(eiFnesTlg.iv-TIetRhhryee) Aconmimpraelssseadssaiigrnseodurtcoe aGsruosuepd f1or(tAheirgecnoenrtarotilo)nroefcethiveetdestanatmeoxsppohseurrees.to air only, from the same tThheewuesiagghet ooff tPhOeSteFstwmasatdeeritaelrmusiendedd,ufroinrgeaecahchdaeyxpoofsutrreea.tment, for each of the three dose group from Tanhdetdwuoraftuiortnheorf eaxdpmoisnuirsetrsaftioorntewrmasinaastiiongnlepu6r-phoosuers.exposure, daily, for 13 weeks for 5 days each week : 300 : TEST ATMOSPHERE GENERATION MIN 313/023622 PpvToadnarniohaepdlemlyoissmTvueyyaretirr/epntiairrnnoaiargfgurFlyeeremluxdpdioiexhrdbrlitarloviueivsEevreepreetrshiryopsypsfelaes.etysth(ntssPAieeetnredlgemls(sctPeuoiTqrdfdueouoFytqrir.Epu,ot)mihfrAeteMetuidnhrdboetotiwdwonsveeagalaasspgctophhor5oaoiu0eausur0vspisgs3eeseeld)dat,rchstoisheinmwnrfttoirhoapnuirirdtgcgitischhheveoetiddtnhcudtcioeaaenhnilldnavicemiveaevndepnbicrodteeilruunordarastiaiilesondetpglnhreoelsetalxayswttdsprlaeaurivrcqocreettupaeisinytdesdegelseclto.anattbbfheeTilrs2nihsots9eyeuhtrgselmis/.ndhymagrditieanenusrugr2itliaeeon2l.cgsamiTztvthehemiadees EubtfcThlhesahoeetacewwdmhfrieeobanteesee-fnlsrtifethntlxhaoeegtnewrradfaoilpcnouopt1lpfwerfaotomlii/pnarrmerhnaietiadaetnaltrpcaueoshottuiedwiotnGilnleedtursrtrocteaaiouhowifpcranan.mafltliFitonbfbaoowercarrrahistrtmweahtoodneaeafsnpdldPtyracooOtoiosilvcefSyniatdFnhglaeeergvcsoaaatasueipumsnpdopmsspputtalotlrihlhynlmiiaggsnan.ihnexcdgatoquaAtmemutrixeavpo.t1lerristailpAysp/cmherttdeecalirsniape2nslue9uietbgrsreereelt/danomdwteetieirufidnatfabheutcfeirilthoneeornnwcotfthhrtisaeoaaoymmlmsfetwx3ebett0pemhaeroser.lss/smubmumrapieasnepieusanlyytstoeasuifntirwenigtmnehagdeas. T30hel/maiirnuctoenftrrooml gthroeubpasreecoefivtheed cchlaemanbear.ir only at a rate of 29 l/minute and a calibrated flow of Fthoeucroenxtproolsugrreouspy.stems were used, one for each of the three dose groups and the other used solely for Fpeorrioadll. dose groups, the syringes were filled with sufficient POSF to complete the six-hour exposure rSecshpeemctaivtieclsyoafntdhethienheaxlpaotisounreexsypsotseumreocphearmatibnegr caonnddeixtipoonssuarreespyrsetseemntaerde ipnreTsaebnlteedA.in Figures A and B EXPOSURE CHAMBERS rbTeohstettroamiinnihonafgltahttueiobcnehsa.emxAbpeocrscureersesspoersciyetsisvteeimnlyc.lucAdoemdfiplatrriiasrteisdounpspsnylyosuteatm-nodnwleyaxstriiannchctoallriapntoieorsan,tewdehxiipncothosuathrtteeacechxhetradamctotbelitrnhsee. atonpd arnadt Asysstcehmemaraetidcesdciarigbreadminoffuartnheerxdpeotsauilrebeclhoawm: ber is shown in Figure A. The component parts of the Inhalation chamber AnTceuhDnmistGrbaielssrvnaoaofpumoat-onuodirnmuilnlyaallreietnaxshppuaporlarsaorutauirotenundsseecodchftbiaoaymnluabsm,etareinna(gciAuhemnDhtGiaaavllilDnoagiyerv2icen0olloenetpsx.tmpruoecsnuttisroenLpctodor,tmsH,paritincsdihniagn,tooHpf easretbcfoatisrodenshuinnircieto,,rpaEonvrgaalrtaiinanbgdl)ea. vvT1oeh(nlteuotimcplah)etateomdob3fcea(rabbspoinputetrsoote.mxdi)mo.naAttehllliysesx4tpu7odsyluitrwreeessr.eecatisDosneusmrihnbagleddd2ou0sspiinnoggr,ts3earaoncddhefnoctrhmeaxmepdobsaeur2r8ewscaemsctdihoioanumss,eeidtdeerninctyiflaiiennddeearnscwlleoivtsheeldas : 301 : Rats restraining tubes MIN 313/023622 MtteThhnuerodobu.auelnsgdTihewmhdeetahrlpeeooetxlahcytpeetconaractsreruhbenreodedonsifatseottcehnateoitoucrbnmbhuseaa.nsml,glybtaaecpnrldeboryseiesdmdaaedbtajyunossninteaosbfeelrpnetduiotsotnho-mofaifatllia"onnOwta"eitnxhrpietnahgnsendsopeeudoatlsspiotllianooslcnytiacotteofbdupthinrneogjt.rehacetAtsefxdpropuumorsihsnutgrhroeerdeptsaoptprraatessirsneeotds.f Csehaalemdbweritlhevaenlsextwpaondaenddpthlarseteicwbeurneg.used to expose the animals. All exposure ports not in use were Air supply and extract Aanidr wsuapspdlireisedw(edreewprpoovinidte~d2bCy).a compressor. The air was filtered to remove any residual particulate Tseeyxxhshhetaaeuucmsasttl.icabofrmtTaethrpeerdbiesaeiinnixrgghflaodauwislFutlteuaexoidrtsfrwolaorcibwttherrfterhcqoeaumrribroetoohdnme vfboaaairprsoteehuxeortrffavitcalhttpe.eor euaxrnpdcoosanucrseielnisctyraasttgeieomln cwaonlauasmlypnsaissbseewfdoartsehrsiootulweglhaysappatarssasspeepddinttoog The inlet and exhaust flows used for each group are detailed in Table A. Tathmeocshpahmerbeevriaaiarnexextrhaacut swt astsacpkr.ovided by vacuum pumps located outside the building that vented to PROCEDURE Fsdspieomesuccirltrarieporxtppiehooxonsctueorpmtetheestthyeasrcttae,ompmfposmlrywettnheortesethcueorsednelotdars,oteilongnggreroouftuoopprs,eottahnhceleyh.rgsaratosmuprpe.lcineTgivheedapnradoircetohdneulrye.FfooTullrhoieewrreefdoTrferoarninsefaotchrhme gfrooIlunlopfrwawrineadgs vTahleueFwT-aIsRzedraot,ascuabpsteuqrueepntrloyg,raambamcke gwroausnidnistciaalniswedasarnedcothrdeepdaathnddtihffeerceenllcpeawthalsencghtehckweads tcoaleibnrsautreed.the ttTsuhyhbereiiPnnsggTye.FrsiETnwghteueerbsepiwnumgmeorapeulsmnstweoeldseetrcoettonetdutth,hrenefieslsdluyerrdofiannwcgbeeirtoihdefrftithlvhyeeeritsnge.lsoaTtsrhssdueefbrrsisttyt.oarinTnecnghegee,satighnweejeetwrcheteeiociggnohenratansrteieoncgttfeoldaibqnteudoiudttsohseewdmvewoarvpaeeosruetthhrcieeosnerldrissqeeudtb.iydanPadTlotFnhEge Tfoofhrtehthereacttshraewmaetmbreeern.retmUgnroouvusepeddafnerodxmpnoustmhuerbeierprceoadrgtfseoswr aeenraedchspealaanlceimeddawli.nitthTohbreleastnturkbaieinnsgiwnpgleurtgeusbt.hees,nwathtaicchhewdetroelceovleolsur2caondded3 Tglhaessitnulbete aflnodwomuettleerts.airflows of the exposure system were calibrated using precision made tapered wTheereccoonrnreeccttiaonnds woofrtkhiengg.eneration and extract systems to the chamber were checked to ensure they The barometric pressure was recorded manually. : 302 : rGcsewoecninottcerindhraueintadiglo.lnyTsyhdcseeoteltmiimvmmeaerete-ncdacoetfnhldtoerwoaclslhreaatdhtmeecbhoesafyrm1raiblnt/emgmreosinswdpurihttiecve.hereirnsfgrwosmyerseteeamtuchrwnteaedssttuocrnhn,aetmdheboenersxtiopmotushlutearentiemsoteua-srcltyoM.tniAmtIrNoeslsal3em1dw3pec/l0rehe2ap3mut6hmb2ee2pnr Atedechxaoetecptne7hotsrrstmmoauelrirxiltnneepu.adoottfsiecAoushenrxlaielmpncotocobhsfheuatarhmPrmeesOb,wbeSeteixhrFtrcpeahotitcimnsinomugonrteehscs-p,eeychtnsohetotnererraetmdrdtsoie.aorlwtlnaeeGdcroraeoccphpuctuuapurmrmer4ebp,sdeeyrd3satsettwaomniewtdxcwaah2acsisntteltgyaocfsrt3ytiohv0smeatetmembFdoiT.ntr-hAeuIdtRtteihrieenaictnnFetaterTelvdyr-avIstlRaehslres.oaftnAetah1snl0rtyoammslueygiirsxnhiatusounturedfetsotrffierrmaoothcmmehe Artcaeehstmcatoihmpnredetbereaeradnvrt.uiaomlrpseaeTolwrshaf.eat3iso0arniemracflilonopruwadtreesadsm,wteahetnrreoyerusrmge(haiencaactsilomuundroesinddbgifytitheetrhdmoeubprlgeaahrtnasoktuutiontregethxapenpludoegsiuxnsrplieeot,utstauaotnrgeeddestohauutestrtlihenwetgiatshiairnmcf-hleloienwlceekrvaseftlloeo)fiwnwgmetehnreeeetercmarhstiaa.onmnubTaaelnhlrydes Armsceyotsirlneiltneuth.cgteeteGisenecng(nodeen1qrot2uaeftinsilsaoitibsmnxrwaphatlieoierorusfenlrofsrrwteoigmcmewoneraeedsatre9ac9dtthui.iorsdnnToe,7shdtehemoegtifrinfsmouyuaetrnpei-n.dsc)got.ehnTetdrhorcielhvleaeddmrastbcawehraecmraeepxbtttueruarrrecnstewpadrilotlocoghfwrfianeamgdnmdtsoyethsctheelaemwlatreewidtghaheastuvsotaowfpmitothcauehtriecrfdeaomlrloya5fifna-afitnn1eg0dr Ahotldthinegecnadgeos.f this time, the rats were unloaded from the chambers and returned to their respective The chambers were washed with hot water. tThhroeuIgRhoceultltpheathexlpeonsgutrhe.was retested to ensure that the initial value prior to the exposure was consistent TEST ATMOSPHERE ANALYSIS (FIGURE B) Acoinr cseanmtrpatlieosnwoefrteheretemstoavtemdofsrpohmeret.he inhalation exposure system in order to estimate the vapour uTarsheienggcivoaennFceTinn-tIArRaptiSpoepnnesdcotirxfoPAphO.oStFominetearir. wDietfhiinnittihvee idnehtaalialstioonf tchheamFTb-eIrRs,oiftsthsetadnodsaerdgirsoautiposnwaenrde vmaleiadsautrioedn vTehnetilSapteedctcraobpihnoetto. meter was located adjacent to the exposure chambers in a separately housed TccmohnesdtiiranumscttreeutdemraeTsnetpfawlortansotufcbtohinnengte.imcteed-cotonteroalclhedseclheacmtebdersasmwpitlcihnigngposrytstbeym.prAogllragmasmseadmspwlinitgchliinngesowf evraelv0e.6s Echaacmh bsearmlpevleelw2a,sthreemsaomveedasfrthoemtraeastpeadreanaimniamlsa.l exposure port through a modified blanking plug at : 303 : MIN 313/023622 CHAMBER MONITORING SYSTEM AwdcsadeonuuatmdrrPtsiainCnptspiggturooetrnrueueserpeanodncn(f(htPeitpanhlCtregeeie)cox-tsnAepratoxuonupnpdsdthiuoyocara.sQaeslulle.Rulr.yeaian.)nwTftTpoThhhrd3ehmae.ai0sstad1aeptpa,riprtoosaaronogingnfrcrtatcewoaemoxmdllalpmlerameoecscestetiuaweoawrdhnenaaasdwrmssdueaFcoqsscoTneuomiIddpetRionypstr.copoihesnlaaemgrydadeonpwodndhfaiaottrsdoheneirrsewapaaelnnemabdrdyeaotsnrhwileiceotceoaosrprnetr.oaedgsdcteStohsbienmeyxotrpufostolhyoltslaespeutnedereSremaopbtudoiyopsanlnetsyaar:o,fraocptnorhefmleorilsnaraoditntitnaiohcaatneeall Setting-up phase Ipfolc/nooamfltntlh2hiojnluewelun/nitemcengdtiititnhooibuanfywltewpatahshiwteabhtahsaetsgech,nakeupsgcsrcraeosyoldmtliuribennpfraddotameetrderssdtcbhaawuynensde.tinrhneAitegthmrnpeoaroguocrnelgeetnirrrmttoaaiamarfeipnienmdduddreueeecsrstyihncnlwyiirgtnelraedeaosnnegceredavonlieiisfnnbpcetrlyenatahdltyiieytn,rdlotdteohgeinneree-wnliwiinannsacsetntsyreitlu.taiurnmposdTeegeerhdnereentsdf,.roetfturlsAhobpetweohreniagsgsmnaeupsaellwuatfyertlasoepressdworscmfuehld.oseerewtceedkwTrrea.hditnee1, Tsahmepsltinugd)ywdeerteaielsnt(eirnecdluadnidngstothreeddianitloythpeatdhaletangctahp,tunruempbroegrraomf msceanpsrioanr dtostahme pelxepsosaunrde.frequency of Exposure monitoring phase rTaccoenhofhcadmwiosmrphsdpbuuiehcetbdehars'.rssereqaeenpuwTndrevhaenieasstrnelosyndtneatamxeartttdfaeeetendr3wnrt27aewelcrmxeaozasiaicpnddmtuilddsyotepiesndls1cai.0tsylocaAermatdeentdrisono.ttduhnautalernsosicnftrhGgetweeraones3u,ltva0ppre-trm3isonaiwfntmeuaadpttsmeleaaocnnpysdaopclihlynseetstrowseerdphegedefernonoldtelnhooreaswtethiaeogendnra.olbloyuyGcspeaGrwdloruehcorpoauernp4drceew2cdn.oartisrrvdEaaeteaindocao,nhlfyewtastehecasdhest The chamber selection was controlled by an time-controlled chamber switching system. Post exposure phase Avatluthese, teongdetohferthweitehxsptoasnudraer,dtdheevdiaattiaoncwolelerectceadlcduularitnegd feoxrpeoascuhrepawraams ectoerllraetecdordaendd. printed. The mean Midac Grams 32 version 4.11 software was solely used to generate a hard copy of the infrared data. tTchaheleibeIrRxatpicooesnlulirfepaantwhyalpsernocgbotlhnesmcisastlewibnirttahttihtohrnoeuoagnfhatohlyuestiFstThh-eaIdReoxwcpcaoussrurrereead.ssdeTusrhsiinesdg wtthoaeseenxtsopuorepsurtorheva.itdteheainsieticaolnvdaluoer pbraicokrutpo Details of the analytical methodologies used are given in Appendix A. : 304 : TARGET CONCENTRATIONS MIN 313/023622 The target concentrations of POSF were: Group 234 Designation InteHrLmoigewhdiddaootesseedose Concentration (P313P000m00 ) The target concentrations were selected in consultation with the Sponsor, following the review of available data and Huntingdon Life Sciences report MIN312/014272. EXPOSURE CHAMBER CONDITIONS Chamber analysed concentration ofPOSF The test atmosphere was sampled from level 2 in each test atmosphere chamber. Each atmosphere was continually drawn through a transfer line at a flowrate of 1 l/minute, which was therefore in equilibrium with the mean concentration from the test chamber. Every ten minutes, air from each transfer line was sampled by the software for automated analysis in the order of descending dose group for data logging activated by the FT-IR AutoQuant software. Each dose chamber was analysed every 30 minutes. When not being sampled, these transfer lines were pumped to waste (Figure B). The achieved chamber concentrations o f POSF are presented in terms o f parts per million of air and were derived from Beer Lambert's Law. The values obtained from the Sponsor's POSF calibration were standardised against validated gasbags by applying a conversion factor to give the vapour concentrations. The methodology and further detail are presented in Appendix A. Chamber spatial distribution All the animals were situated on levels two and three of the three level exposure chamber. The analytical sampling point was situated on level two of the exposure chamber. The spatial distribution o f vapour in the chamber was checked between chamber levels 2 and 3 during preliminary trials for this study. A difference in concentration of less than 2% for all dose groups with varying chamber level was observed, which was well within the 10% tolerance limits normally allowed for the analysis of such exposure systems. Nominal concentration of chamber atmospheres Each chamber nominal concentration was calculated from the mass of liquid used over the six-hour exposure period and the exposure mean airflow. The ideal gas equation was used with the molecular weight of the liquid and the measured chamber conditions to compute the volume of vapour produced from the mass o f liquid used. The calculation is detailed in Table C. The nominal concentration is presented in parts per million o f air. Airflow and temperature These parameters were recorded manually, as described previously under the Test Atmosphere generation and Procedure sections. : 305 : RESULTS MIN 313/023622 VAPOUR CONCENTRATION The data are presented as follows: DInadiilvyidmueaalnvvalauleuses TAapbpleenBdix B pTrheesesntuteddybmeleoawn:concentrations (the mean of daily mean values) for each group exposed to POSF are Group 2 ChTaamrgbeetr concentratiAonna(lpypsemd) 30 26 34 100 104 300 299 tT(lc1hoLo5hewno.e5cw,aaeinn6nndc.ata4orrllayseyateassin)oisesdidnwnr.5geca.sos3un%dloctinesfffnloiydtcrruuamrGltitianyrorogngusieopnxwfsaple2olcry,seo3unbirnteaerlnsorodelw8lai4nsaog1(nnL0da%otbhw1l0eyf,.rIogTntmeohtesoetrtdmhceamoegedtarfaietfareietgcremieiaetaelnnnctdtsofwneHoecifidetghvnhattrrraadairattogeitsoieeontswn,)cpioroteanhfrscttpelhdyenecetrtdcdairuvateieieoallysnytoisnma.gunendGauvnrrsoaeuwpufalopeelurlcy2ert NOMINAL CONCENTRATION The data and equation are presented in Table C and summarised below: Group 2 concenNtoramtiionnal(ppm) 31 A/N ratio (8%6 ) 34 103 101 305 99 A/N = f ( Analysed Nominal ccoonncceennttrraattioionn'))x 100 TofhPeOnSomF idneallivceornecdeinnttroattihoengfeonreeraatcohr.exposure period was calculated for the test group from the mass tHnbtTToheoofhhisegmtteethehssiAsetnugutdxabr/dopNomlsyseutea,cacprstonatssee)ntch.ridecsoioaheTumrlnfoelhodetswdirriasuadebnGtridueiinonrredoeanagsixtupscibtcpopahefesrtoei2leonlrosxegi(fnniGLcmritaooetrniaaontwaaatgusleilirpnyldsepystesoereedismn31mdecw0e)iayt0nnoiwn%ttgvhdanwaisoonpf4iomfotlthro(hutiIhwneratneihlaetslgielrasierdntctmnivohlooeeasaennrtelndaculoitegeiaienfno.rtxeoettnprhsuTaeesapthtcyniosteotsdeetnatsedchHntmo(ebdmAei.gufvG/afhtNaitcrecp)odirao,eiuonuanesplrtxbesisaspse)ne3roaerdfwacspvsvncereaoedridrerouiy4anralttelst(ieioosItdanstnlttespfhteoheerlframriokcnsbreeetyadtnl7hirit.thtaea5hotg%oeemoefdlaeotffnhaooosndesrrf : 306 : eexxppoossuurree.. This effect is more marked for Group 2, where less test material is used MovIeNra3ll13du/0r2in3g62a2n CHAMBER TEMPERATURE The daily mean chamber temperatures are presented in Table D. The chamber temperatures were similar for all groups on each day of the study. DISCUSSION r4Cfaoot(reIn.nGttreroorlmuopefd2tiha(etLePoaOwnSddFHovsieag)phordeuofrlsedecest)l.itvhTeehryeditlfoofiwtchuevltayepxoipnuorscucoornentrccoehlnlaitmnragbtietohrnse watenasdst tgmhoeaotd1er5ei.a5slp%einccpioauletlfyfaitfcoiaernvGterrooyfuvlpoaswri3aftaeionendd bOacuoenttnwosmoiescetacentaentsdthiAoedna/aNtnaparrclaoyatbspioeltedu)mrtaehsn.adWtwnthhioteehmraeitnnhniaemol acaalonsnnaawcllyeyetnsriitecsraaeltoxidocpancotussarewrwdeadatsos. oatbhvsMeaeircolvaosebrtdlree.o,cftitcthiosenrsceeeansptorranotabibollenem, tasos araesslgauotmeodeda(igurersecinetlgmytehtnoet CALCULATIONS Itffhniogeruoprdrredai,entaprtiotnionsgs.mitbhiClinysoimrlneesiapsedoeqirunttheghnetatolcsyus,bmmethueaenllalstecaivaprleopcuauernlreadrnoteetrddsd,nicswuocmhnreitbcpineharunsrocemuisesuasllyytwfuiirntsochimnluogdtrheeuepnrreroaodutuanetnddadirinenogduthnenerdurimornergbpseooirrnsft.tnahunemdlabosentrlssy,igmrnouiufcnichdaeondtf : 307 : FIGURE A Schematic of a rodent inhalation dosing system MIN 313/023622 bKdeacfg eyAPEGTSSoiyxeilnarlrspytistosenpscursgroVupeodmprpiaedalpypyrmcolioevhueuneatrneermidsrsebyfreerreindgleine hi j kml BRwEFAOixloiiblartthdshnraeeeak2xurntivi0tstnoratragnetepcixsoplteptlnrunoapgusiunosmrirnet gpoturbtseson(slteavnedlasrd1tsoec3t)ions : 308 FIGURE B MIN 313/023622 Schematic of a Fourier Transform Infrared spectrophotometer and the sampling system Kbaced eycNF1ETh0letaiohtsmcrwytmoblcmgeeoIneremRnetepiccrnoeyrullneliningtddruoelsagratemendpclteoylli1innlde/mefrrionmute jhkfgi FFDTTSlTaioiomamg-wpIgepRhml-lerceaseoVpgtlnieemantrcrlevtorprerelouelgsepmtuduhlproacnttheotadommtweobtaee2srrtles/wmiitncuhtieng system : 309 TABLE A MIN 313/023622 Operating conditions for the inhalation exposure system Parameter Target concentration of POSF (ppm) Chamber airflows (l/minute) EClhuatrmiabteorreoxuttrpauctt (chamber inlet) Vapour generator settings Sinter diameter (mm) Test material feed Syringe size (ml) N/A Not applicable 1 (Air control) 0 Group 23 (Low dose) (Intermediate dose) 30 100 4 (High dose) 300 29 29 29 29 30 29 29 29 N/A 114 114 114 N/A Precidor 5003 syringe pump N/A 5 20 50 310 : TABLE B MIN 313/023622 Chamber concentration of POSF (ppm) - daily mean values Exposure Analyser Concentration (ppm) Actual Concentration (ppm) no. Gp2 Gp3 Gp4 Gp2 Gp3 Gp4 i 2 3335 114 117 332570 22 21 8879 226719 345 21-3 36 132 302 23 101 240 61 7 42 147 393 28 114 315 8 22 127 363 12 97 290 91 1110 21 41 130 147 359 380 11 27 110104 238074 12 1134 41 4432 132 132 124 337609 365 2279 28 110012 95 222999562 1156 3456 114406 337980 22 31 110182 330133 1178 4452 112235 337716 3208 94 96 320917 19 43 125 381 29 95 305 2210 4 44 40 126 117 337564 29 26 96 301 89 283 22 23 4402 120 129 385 386 26 28 91 308 99 310 24 25 26 345188 114233 135 339634 365 41 25 27 111 19044 322199152 27 28 41 42 136 133 363 373 27 28 110052 290 299 29 30 42 44 134 137 378 371 27 103 303 29 105 297 3312 41 39 113450 382 368 2275 110084 329056 3334 1 35 40 41 139 135 371 387 26 107 297 27 104 310 3367 38 344902 134 134 137 336892 389 2266 110033 239056 28 105 311 39 40 4412 146 137 396 386 27 113 317 28 106 309 2 34 NPErtohobydllaeetnmaecwioniltlnehcitetretohdgyedlenuneceatoliinbcrnoaimttripooungtecenrylcpianrldoibberrlearmtaionwnoicuthytlidnadtaerc,anpotudraetapraongarlaymtimcael data collected New Ethylene in nitrogen calibration cylinder : 311 : TABLE B MIN 313/023622 (Chamber concentration of POSF (ppm) - daily mean values - continued) Exposure Analyser Concentration (ppm) Actual Concentration (ppm) no. Gp2 Gp3 Gp4 Gp2 Gp3 Gp4 41 42 3378 112374 352 342 24 25 19037 228713 4434 41 36 113319 336559 2237 110017 292 287 45 40 138 358 26 106 286 46 47 40 40 114318 336602 26 107 288 26 109 290 48 3 39 129 364 49 37 133 357 2254 19092 291 285 50 51 37 40 114316 336774 23 104 293 26 109 299 52 5534 42 40 40 142 114464 347035 380 2276 26 111110139 239294 304 5556 3399 114402 374 378 2256 110180 230939 5578 42 41 114359 337715 2287 112 107 239070 59 36 140 383 23 108 306 60 61 39 48 145 147 349232 2352 111124 315 339 62 6634 4444 46 114318 138 378 441131 29 106 302 29 109 331 31 106 329 65 66 4432 137 139 406 415 28 106 326 28 107 333 67 40 146 403 26 113 323 OMveeraanll 40 135 375 26 104 300 sd CV (%) 142..19 8.1 6.0 205..24 145..02 66..64 16.5 5.5 Mean (1-65) 40 135 374 26 104 299 sd CV (%) 5.0 12.3 8.1 6.0 159..24 4.1 15.5 66..64 15.9 5.3 Ethylene in nitrogen calibration cylinder ran out sd Standard deviation CV (%) Coefficient of variation (sd x 100/mean) : 312 : TABLE C MIN 313/023622 Nominal concentrations of POSF (ppm) - individual and mean exposure values The following footnotes relate to Table C and are as follows: 1 2 5 NProobdlaetma cwoiltlehcetethdydleuneetoincnoimtrpougteenrcparloibbrleamtiownicthylidnadtaerc,anpotudraetapraongarlaymtimcael data collected Nominal concentrations were calculated from the following equations: Concentration (ppm) = -V--a-V-+---V- x 10 6 TV>.= -W----x-M-R---x--T- x --7-6--0-A-m-t-m-m---H--g- where V = gaseous volume of POSF W = mass of POSF MR == molecular weight POSF (502.14 g/mole) gas constant (0.08205 l atm mol'1K'1) ATtm == temperature (K), = temperature (C, see Table D) + 273 atmospheric pressure (mmHg) Vthae exposure volume of air (litres) passing through the chamber during A/N Analysed/nominal concentration ratio expressed as a percentage sd Standard deviation CV (%) Coefficient of variation (sd x 100/mean) 313 : TABLE C MIN 313/023622 (Nominal concentrations of POSF (ppm) - individual exposure values - continued) Group 2 (Low dose) - Target concentration 30 ppm Exposure Time Period Barometric Test Compound No. (mins) Pressure (mmHg) usage (g) 1 360 773 5.42 2 360 759 5.58 3 360 759 5.59 4 360 765 6.19 5 360 757 6.13 6 360 751 6.05 7 360 756 6.04 8 360 756 6.45 9 360 756 5.91 10 360 773 6.00 11 360 771 6.06 12 360 770 5.91 13 360 774 6.66 14 360 773 5.67 15 360 775 5.25 16 360 775 6.84 17 360 770 6.62 18 360 771 6.53 19 360 766 6.71 20 360 776 6.43 21 360 761 6.82 22 360 762 7.01 23 360 755 7.00 24 360 754 6.33 25 360 755 6.57 26 360 744 6.74 27 360 767 6.27 28 360 765 6.90 29 360 767 7.00 30 360 761 6.89 31 360 759 7.07 32 360 760 7.05 33 360 760 7.12 34 360 760 6.86 35 360 765 6.75 Analysed (ppm) 22 21 231 2 1 28 121 11 27 27 29 28 22 31 30 28 29 29 26 26 28 41 25 27 27 28 27 29 27 25 261 27 Nominal (ppm) 5 24 25 25 27 27 27 27 29 26 26 27 26 29 25 23 30 29 29 30 28 30 31 31 28 29 31 28 30 31 31 31 31 32 30 30 A/N ratio % 92 83 93 103 40 41 101 104 98 112 97 104 103 97 96 104 85 83 88 143 84 87 96 91 89 96 86 81 83 90 : 314 : TABLE C MIN 313/023622 (Nominal concentrations of POSF (ppm) - individual exposure values - continued) Group 2 (Low dose) - Target concentration 30 ppm Exposure Time Period Barometric Test Compound No. (mins) Pressure (mmHg) usage (g) 36 360 762 6.92 37 360 761 7.11 38 360 751 6.96 39 360 757 13.79 40 360 748 6.77 41 360 773 7.21 42 360 775 7.02 43 360 779 6.98 44 360 768 7.03 45 360 765 6.92 46 360 768 6.85 47 360 768 6.85 48 360 768 6.98 49 360 768 6.83 50 360 767 6.67 51 360 745 7.30 52 360 757 7.16 53 360 762 7.31 54 360 764 7.29 55 360 765 7.25 56 360 760 7.19 57 360 768 7.28 58 360 757 7.37 59 360 758 7.63 60 360 756 6.67 61 360 761 8.01 62 360 755 7.94 63 360 757 7.99 64 360 756 7.98 65 360 748 7.98 66 360 750 7.86 67 360 758 7.32 Overall Mean 360 762 6.91 sd 0.0 8.0 1.059 CV (%) 0.0 1.1 15.33 Analysed (ppm) 26 26 28 27 28 24 25 27 23 26 26 26 25 24 23 26 27 26 26 25 26 28 27 23 25 32 29 29 31 28 28 26 26 4.0 15.2 Nominal (ppm) 5 31 32 31 61 31 31 31 30 31 31 30 30 31 30 29 33 32 32 32 32 32 32 33 34 30 36 35 36 36 36 35 32 31 4.8 15.7 A/N ratio % 83 82 88 44 91 76 81 90 73 84 87 87 82 78 80 77 86 80 80 78 80 87 83 67 84 91 82 81 88 78 79 81 86 15.1 17.5 : 315 : TABLE C MIN 313/023622 (Nominal concentrations of POSF (ppm) - individual exposure values - continued) Group 3 (Intermediate dose) - Target concentration 100 ppm Exposure Time Period Barometric Test Compound No. (mins) Pressure (mmHg) usage (g) 1 360 773 19.77 2 360 759 19.88 3 360 759 22.27 4 360 765 19.59 5 360 757 25.55 6 360 751 25.57 7 360 756 23.57 8 360 756 23.23 9 360 756 23.01 10 360 773 23.12 11 360 771 22.81 12 360 770 21.67 13 360 774 20.53 14 360 773 19.68 15 360 775 21.91 16 360 775 22.51 17 360 770 19.18 18 360 771 19.34 19 360 766 20.10 20 360 776 19.89 21 360 761 20.96 22 360 762 20.81 23 360 755 21.34 24 360 754 20.80 25 360 755 22.48 26 360 744 23.19 27 360 767 23.65 28 360 765 22.63 29 360 767 23.10 30 360 761 23.06 31 360 759 24.23 32 360 760 23.73 33 360 760 24.96 34 360 760 23.72 35 360 765 24.28 Analysed (ppm) 87 89 1011 2 1 114 971 100 114 101 102 95 108 112 94 96 95 96 89 91 99 111 94 104 105 102 103 105 108 104 1071 104 Nominal (ppm) 5 86 88 99 86 114 115 105 104 103 101 100 95 90 86 95 98 84 85 89 86 93 92 95 93 100 105 104 100 102 102 108 105 111 105 107 A/N ratio % 100 101 103 108 94 99 114 107 113 110 113 115 112 113 107 111 96 99 103 119 93 99 100 102 101 103 100 99 96 97 : 316 : TABLE C MIN 313/023622 (Nominal concentrations of POSF (ppm) - individual exposure values - continued) Group 3 (Intermediate dose) - Target concentration 100 ppm Exposure Time Period Barometric Test Compound No. (mins) Pressure (mmHg) usage (g) 36 360 762 23.91 37 360 761 23.52 38 360 751 23.08 39 360 757 24.10 40 360 748 22.49 41 360 773 23.13 42 360 775 24.36 43 360 779 24.50 44 360 768 23.87 45 360 765 24.32 46 360 768 24.68 47 360 768 25.88 48 360 768 22.68 49 360 768 23.43 50 360 767 24.83 51 360 745 25.30 52 360 757 25.01 53 360 762 26.15 54 360 764 24.59 55 360 765 24.67 56 360 760 25.31 57 360 768 25.66 58 360 757 24.37 59 360 758 25.91 60 360 756 25.48 61 360 761 26.38 62 360 755 25.10 63 360 757 25.69 64 360 756 24.21 65 360 748 24.77 66 360 750 25.28 67 360 758 26.72 Overall Mean 360 762 23.37 sd 0.0 8.0 1.958 CV (%) 0.0 1.1 8.4 Analysed (ppm) 103 103 105 113 106 97 103 107 101 106 107 109 99 102 104 109 109 113 111 108 110 112 107 108 112 114 106 109 106 106 107 113 104 6.6 6.4 Nominal (ppm) 5 106 104 104 107 101 101 106 106 105 107 108 114 100 103 109 115 111 115 109 109 112 113 109 115 114 117 112 114 108 112 113 119 103 9.0 8.7 A/N ratio % 97 99 101 105 104 96 97 101 96 99 98 96 99 99 96 95 98 98 102 99 98 99 98 94 98 97 95 95 99 95 94 95 101 6.2 6.1 : 317 : TABLE C MIN 313/023622 (Nominal concentrations of POSF (ppm) - individual exposure values - continued) Group 4 (Hig i dose) - Target concentration 300 ppm Exposure Time Period Barometric Test Compound No. (mins) Pressure (mmHg) usage (g) 1 360 773 65.85 2 360 759 60.94 3 360 759 50.67 4 360 765 68.06 5 360 757 69.55 6 360 751 70.10 7 360 756 64.39 8 360 756 63.86 9 360 756 62.01 10 360 773 65.30 11 360 771 64.25 12 360 770 60.48 13 360 774 64.10 14 360 773 61.10 15 360 775 68.94 16 360 775 64.94 17 360 770 65.16 18 360 771 67.11 19 360 766 66.48 20 360 776 64.43 21 360 761 66.92 22 360 762 71.42 23 360 755 68.98 24 360 754 68.06 25 360 755 68.86 26 360 744 67.64 27 360 767 67.39 28 360 765 68.07 29 360 767 68.92 30 360 761 66.93 31 360 759 71.21 32 360 760 68.58 33 360 760 69.77 34 360 760 71.58 35 360 765 72.73 Analysed (ppm) 261 279 2401 2 1 315 2901 287 304 296 295 292 303 313 301 297 305 301 283 308 310 315 291 292 290 299 303 297 306 295 2971 310 Nominal (ppm) 5 288 272 226 301 311 316 288 286 278 286 282 265 280 267 301 284 286 294 294 281 297 317 309 305 308 307 297 301 304 297 317 305 310 317 321 A/N ratio % 90 103 107 109 101 100 108 111 105 109 101 110 105 101 104 107 95 97 100 103 94 95 98 99 100 100 96 97 96 96 : 318 : TABLE C MIN 313/023622 (Nominal concentrations of POSF (ppm) - individual exposure values - continued) Group 4 (Hig i dose) - Target concentration 300 ppm Exposure Time Period Barometric Test Compound No. (mins) Pressure (mmHg) usage (g) 36 360 762 69.30 37 360 761 71.16 38 360 751 68.29 39 360 757 69.06 40 360 748 68.35 41 360 773 68.52 42 360 775 67.52 43 360 779 69.51 44 360 768 69.42 45 360 765 68.12 46 360 768 68.72 47 360 768 67.79 48 360 768 66.76 49 360 768 67.16 50 360 767 69.87 51 360 745 72.90 52 360 757 70.84 53 360 762 53.96 54 360 764 72.94 55 360 765 70.93 56 360 760 72.86 57 360 768 71.65 58 360 757 74.47 59 360 758 79.85 60 360 756 73.32 61 360 761 78.25 62 360 755 76.65 63 360 757 77.41 64 360 756 73.64 65 360 748 77.28 66 360 750 78.12 67 360 758 77.61 Overall Mean 360 762 68.76 sd 0.0 8.0 5.141 CV (%) 0.0 1.1 7.5 Analysed (ppm) 295 306 311 317 309 281 273 292 287 286 288 290 291 285 293 299 299 324 304 299 303 297 300 306 315 339 302 331 329 326 333 323 300 16.5 5.5 Nominal (ppm) 5 307 316 307 308 308 299 294 302 305 301 302 298 293 295 308 330 316 238 322 313 324 315 332 355 327 346 342 345 328 348 350 344 305 23.8 7.8 A/N ratio % 96 97 101 103 100 94 93 97 94 95 95 97 99 97 95 91 94 136 94 96 93 94 90 86 96 98 88 96 100 94 95 94 99 7.2 7.3 : 319 : TABLE D Chamber temperature - exposure mean values MIN 313/023622 Temperature (oC) Gp1 Gp2 Gp3 Gp4 (Control) (Low dose) (Inter dose) (High dose) 1 20.8 20.5 20.4 21.3 2 34 2200..35 20.7 222000...964 20.4 20.2 20.3 222110...139 5 20.4 20.5 20.3 21.2 6 20.6 20.3 20.0 20.9 7 8 22.0 21.7 2200..34 2200..34 2211..32 9 10 21.3 21.8 20.2 20.2 2200..34 21.5 21.0 11 12 13 2222..30 21.3 2200..58 21.0 2200..32 20.4 21.2 20.7 21.0 14 15 2211..33 2210..08 2200..30 2210..09 1167 2211..33 2200..00 2200..34 21.2 20.9 18 21.3 20.0 20.0 21.0 19 21.4 20.9 20.4 21.2 20 21.3 20.0 19.9 20.9 2212 20.9 20.8 20.0 20.0 20.0 20.0 20.8 20.8 2234 21.2 21.0 2200..80 2200..30 2200..89 25 20.9 20.6 20.0 20.8 26 21.0 20.5 20.0 20.9 27 21.0 20.8 20.3 20.8 28 29 21.3 21.7 20.7 20.7 2200..02 20.8 20.9 3310 2200..88 2200..87 20.2 20.1 2200..96 3332 2200..88 2200..57 2109..09 2200..54 34 20.8 20.3 19.9 20.0 3356 37 2200..89 20.0 222000...042 2109..09 20.0 222000...544 38 20.2 20.4 20.4 20.8 39 20.0 20.3 20.0 20.5 40 20.0 20.2 20.0 20.4 : 320 : TABLE D MIN 313/023622 (Chamber temperature - exposure mean values - continued) Exposure Temperature (oC) no. Gp1 Gp2 Gp3 (Control) (Low dose) (Inter dose) 41 20.0 20.2 20.1 42 4434 2200..30 20.0 2200..54 20.5 2200..14 20.3 45 46 20.3 20.3 2200..44 20.2 20.1 47 48 19.9 20.0 20.3 20.7 2109..29 49 50 2200..32 20.4 20.3 20.3 20.0 5512 53 2109..09 19.3 20.4 2109..34 20.2 2109..02 54 55 2200..00 20.4 20.0 20.2 19.9 5567 58 2109..09 19.9 2109..29 20.3 222000...002 59 60 20.1 20.0 20.6 20.1 2200..32 6612 19.9 20.4 19.9 20.3 19.9 19.9 63 19.9 20.3 20.0 64 65 19.9 19.9 2200..02 20.0 19.9 66 19.3 19.8 19.5 67 19.0 19.5 19.6 Overall Mean 20.6 20.4 20.1 sd CV (%) 03..741 0.33 1.6 0.23 1.1 Mean (1-65) 20.6 20.4 20.1 sd CV (%) 03..267 0.31 1.5 0.21 1.0 sd standard deviation CV (%) Coefficient of variation (sd x 100/mean) Gp4 (High dose) 20.3 20.4 20.9 20.5 20.4 20.8 20.7 20.3 20.4 20.5 20.4 20.7 19.6 2200..56 2200..88 20.1 20.3 20.0 19.9 19.8 19.9 20.0 19.9 19.0 19.0 20.6 02..450 20.7 0.42 2.0 : 321 : APPENDIX A Methods of sample collection and analysis for POSF MIN 313/023622 SAMPLE COLLECTION Chamber concentration EtcchhhaeaacmmIhRbbceechrrealalmstwambnieotdcrshpsaiuhntbemgsreeosqswypushaetsneemrtdleyrawapwtuanmsatphrceeroogdnuuttigolnahutweatdahllseytfeIl.oRdwracwerlanlteaftrooamfre1geual/lcmahteindtuefsteltowuchsrianamtgebaperolsatiobtiootrnhaeetodrtydimopweu-ncmsotpnr.etraomTllehodef tTTlhinhhreeeosuscgwaohmneorcpeueltnePdteTraaaFcttihEmonotoufsobptfhihnePegrOee(xS0wpF.6oasswcumpareussdmdiuaepsmteeidnermgtteoiran)w.ecdaasliatbetr.aeTxteahdcetilanyi-rl3finl0oewmtaitnpouetrtehedeintsutpeberevcatgrlosapsthhforlootowumgmheeotteuertr.weGaacsahsmesoxapnmoitpsoluirrneegd. The sample line from each test chamber was located on level 2 of the chamber. METHOD OF ANALYSIS tCdhehetaaemilnebdde,ortfoattghmeistohAsepprhpweerinetdhsixaam.supmlems wareyreofatnhaelymseedthboyd evxatlriadcattiivoen,FiTn-tIhRe. ITnhhealmateiothnoAdnoaflystaimcapllPeraoncaeldyusries aist 322 : APPENDIX A MIN 313/023622 (Methods of sample collection and analysis for POSF - continued) CALCULATIONS FT-IR analysis The samples of chamber atmosphere were passed through the IR cell, which was calculated using the Sponsors electronic standard from Beer-Lambert's Law. A conversion factor was applied to the AutoQuant concentrations obtained with the Sponsors electronic standard to convert these values to the actual vapour concentrations. This arose from a discrepancy of between 23% to 47%, increasing with vapour concentration between validated gasbags, nominal chamber concentrations and the AutoQuant concentration. The equation used for the conversion calculated from validated gasbags and given below as equation 1, had a correlation coefficient of 0.9995 over the POSF concentration range. Vapour Concentration (ppm) AutoQuant Concentration - 8.2414 1.2219 (1) This difference in values was also apparent during Huntingdon Life Sciences report no MIN312/014272 but to a lesser degree, therefore, the introduction of the time-controlled chamber sampling system may have partly resulted in the increased discrepancy. Other difference in these values is attributed to a combination of uncertainties as follows: - POSF reference spectra and subsequent AutoQuant method calculations. These have errors o f 5% associated with them (responsibility o f the Sponsor); - The cylinder o f ethylene in nitrogen standard has certified errors o f 2%; - Pressure drop in the IR cell; - The effect o f using ultra pure nitrogen for the background scans (rather than the control chamber atmosphere) is unknown. The uncertainties relating to the analysed and room air concentrations were estimated by the data capture programme based on the least squares statistics. The method for calculating the concentration of POSF from the mass used to prepare each vapour standard using the nominal feed rate is given below in equations 2 and 3. Concentration = -V--a-V-+---V--x 1,000,000 ppm (2) where VV W M R T -W---X--M=-R---X--T- X = = = = 760 mm Hg Atm gaseous volume of POSF (ml) mass of POSF (g) molecular weight of POSF (502.14 g/mole) Gas constant (0.08205 ml atm mmol-1 K-1) temperature (K) (3) Atm Va == atmospheric pressure (mmHg) volume of air (ml) : 323 : APPENDIX A MIN 313/023622 (Methods of sample collection and analysis for POSF - continued) COMPOUND SPECIFIC INHALATION ANALYTICAL PROCEDURE FOR POSF The analysis of POSF (Perfluorooctane sulfonyl fluoride) in air sample substrate mThoenimtoeritnhgodcoonudtiltinioends iinn athnisIndhoaclautmioennTt ohxaiscobleoegny vstauldidya.ted and is considered fit for the purpose of TfaarmnhoaimeslnydsdteemodscetunumatsstmeinanongtsdpdtahhedteeadrieilMtssi.oItnDhsTeAwhbCeiallsrIibec-seSupedlrrteiiotenacsgieldessduparmewecspittrlhfoeoispnr,hatoohstfeoumapappenpltaerelmoryxseiainmsntadaortyfeAPdcuOootconSuQcFmeunesatnanrtmat.tpisolonefdt2wb4ay0reet.oxtSr3ta6uc0dtiyvpepsmpFeT,c-iafIriRce NatOprTeEsenTt,hrbouutgwhiollubt ethiinscdluodceudmiennat, Sthtuedsyymspbeoclificinsudpicpalteemsethnta.t the relevant information is not available EFFECTIVE FROM: 29 August 2001 Test substance POSF, perfluorooctane sulfonyl fluoride has the following formula: C8F17SO2F. Appearance Clear liquid Storage Ambient temperature Reagents Air In House Compressed Ethylene in nitrogen Sponsor Calibration gas (certified 2%) Nitrogen Sponsor Calibration gas (certified >99.9995%) Liquid nitrogen BOC Cooling Medium : 324 : APPENDIX A MIN 313/023622 (Methods of sample collection and analysis for POSF - continued) Equipment Balance and Data printer Sartorius R160P with YDP-01 Flow meter IGnisltmruomntents 0-4 Lpm FT-IR MCoidrpaocration I2001 series (serial no. 151) Computer Compaq LTE5400 Sotware MCoidrpaocration AutoQuant Version 3.01 Midac Grams 32 Version 4.11 Chamber ADG 3 level snout only Syringe Driver Precidor Type 5003 UV Quartz Cells MCoidrpaocration ZnSe Gas Cell General laboratory glassware Aexchcaeussstopriuems pasl.so employed are: a vacuum pump; cylinder regulators, power connectors; regulated Consumables Syringes Aldrich 50 ml polypropylene Method of Sample Measurement AtgchhievavemovalabupecmoroeunarcloioesnfnegtrPrOatahtnSieodFnsafioemsdfpd3ldi0esip,rleei1cnn0tes0leyadotirnaf3rtfoo0lmo0twphtpehrmeacthetienaosmatfnbd1erarlui./rmmsTtirnhieneuattometeadsotif5rea03ctm0mtlllyo/msstyhpirhrnioenuurgteegeh.aisiTtrhfhdeleroaIwRwsy,nrcmienflirglx.oeemddtrthihvoeerroeuixsgphsolesyturtioen Production of a Background Scan Adasppraepfwclrotornwxutimrhmao.taeutgeolhyf tlhle/evmeIirRnyuct2eellu.selAtcrofatn-epdrusarepanendriitorocdogonentfin3(u-c5oyulmisnlidyneurtceoNsl,ole.acnCteF0dTC-f7Io7Rr00s3i22n1g9slec(anbniestaromtgoesnpper>oc9dtr9uu.c9me99ias5gceon-2ea%rdad)teeidds : 325 : APPENDIX A MIN 313/023622 (Methods of sample collection and analysis for POSF - continued) Storage of standards and samples Stability experiments were not required for on-line analysis. Calibration and Quantification TeeaqhcuehaAtisoaunmtobpQeleuloamwnte(asBsyueserteermm'seLcnaatw,lc)tuh:leataemd oaucnotnpcreensternattioisndfeotreremacinheadbsfroormbanthcee mabesaosrubraenmceenstamaspfloelluoswinsg. Fthoer Where Aa b Amount(ppm) A axb paadbbaetssrhioovrrlebpedatningofcrtnohemcoaotftehatfhefgeicriveicefeeennlrltefd(nraeecbrqeisuvoceerandplctifibyrvroioatmtyfi)oPcnOoalftSirPbaFrOnaisStnfiFeotrhnesidntsaaatnthamdeaprsldeamsspppeelcecttrrsuupmmectrum, which is : 326 : APPENDIX A MIN 313/023622 (Methods of sample collection and analysis for POSF - continued) Calibration of Cell Path Length Calibration of the cell path length is performed daily before each exposure. Amt2ahn%eedct)ehcdraoitseldiitfbpeiureraasmdsetsiidcoenodnetontccthypherleenoirntufrcdoagaetrhlirmio.btnhreaeaotecfsdhaemtschppeyellllicentnprgaealtshiyan-snltenaenilmtygrsotihpgs.r.einoTCrh(eectolyleltisphnaaydmtlehepr-nllNeeenovcg.oatllChule0eicCstiis9oa7rne0catr0oid8ti7ccf4rhaolem(ceikntthphiyuneltsettnetrouestm=tcheee2nr0ttai2frnie0acsplapyptoetmincosanel AAsceafclttioeebrnsrtdaatsaetpdamenprodiasotpchdholenoertnfeing3out-ho5f.ueTmstlhhyiyinslucevotnealeslleu, icenateisnFditTthfr-oeoIrngRe3en2snitnaesgtcrelaaednsfbilnoettoawomrptahrtoesepdPeuoOccfteSr1uFamlm/lmeiessitnshugontedoeniefsiisyrlaedtsearpdanewdcatnmpruptamhrnor.uoxaTuimlglhyhaistretephlcyreooredIdRvueecdrce.yesll2a. QC Pc1a4al0tihb0r-a6let5ino0gntchsmtiL-l1lirmdeogietisso:nn-oTotrhceiofnctfaholeribmpr,aattaihlolnloefwntgihltelhbcveaallirubeerpaeitasioteondustbesityduetphtehpeaursareamrnegitfeenr0so.1wp0ie0lal kbtoeis0c.hp1er1ce5kseemndt.. iInf tthhee QA pIef(crennheotrsdehmitcoyrokdlutfehssmntethaeseehninn=doeitawxt2irCpa0edold2ass.c0luitapbhrlpeiarbm.tarttaIihntoiesno2tnfr%Ciunvm)haa.elleucTncketah:loecibTaf2lrthi%ahbeterioacvetanatilhloiugybnealrevcainhetsieeoitcnhniknsesiidsnpaeiratrerettovhhwgeelreiei5tnfnh%igeicntdytholialvn5nead%rdlaeu.nrseuRc(sbeceysdpleliieiqmfntfuieditetriesonerdntaNllyoblooyrf.wetCcwleeo0dosrCsdaf9etsoh7duqa0ruan0hta8o2lt7ihu%t4yer The temperature of the test gas stream and the barometric pressure will be monitored manually. FT-IR analyser specification ITdrehvteienceMt,oirCdAamc)osIno2i0ftot0wr0sarsteheerisieuasbseFsdoTr-fbIoaRrnacslelpeioncfftrraovrpaehrdioodtuoasmtaecathecerqmuhiiacssiatliaobnwoanandvdse.lqeuAnagunttthoifQiacucaactiunortna.vcyersoifon0.53c.0m1'1.(MAIDMACCT, wThilel gleivnegtahloinfetahrereIlRaticoenllshoirppbaetthwleeenngtahbs(oarpbparnocxeimanatdelcyon1c0enctmra)tidoinc.tates the concentration range that tmTcghoahoesnendoisoupttopcreerttrieeaamddmtiunbamgytatnpphfdrlraooetwctchfeilsedroiauowtrrneeemrsfasotattareoiinntrthedoleedesarIpsvRriososticxedereielmldltauiaifsnrlfndet1oergedl/tnlmhactesoeisnsFuitTnohte--fel,IicRnweeexlhslpryipocoshtrtsaeeummisrsse.eustreeseTtry.shbs.Feyteuamarntfhaleleoyxrwshdeamreutdesatrti.elasrwAcaslanln1delba/xemllhoiatnhubuesttateainnlfiaernlodeymssfirsotahmriees : 327 : APPENDIX A MIN 313/023622 (Methods of sample collection and analysis for POSF - continued) Raw Data RtIadshftniaoeradwereFcrdudtTdaonat-irenItytadRitmhmiissmeeaydymfshietaleefebrmiddenfi.oeacudrtoTemsplheayaydsetawtrYthfaotaeYwesrgfMniepdronrMasitettnarDohtaibaitDnsetrgad.pt.iaxnrcAiteohn.dnpateyrteddhloreuocucsouttirppgnouyhgnt,iatcowhpbbehrtaaiiMnccinkhteIeuDrdwpfAiiaclmuClolmptb,Gyeetrdhoasiefimagttehsnellieey3sdc2tifrsaoosnslonladofivctwwedcdiaaontrtepgeodyd.atfhanEretdoaxmlpwoaoccitslhqaluleurbizezseiiipptdsiodiadgrntrainivbveeidyes. Computer hardware: Computers and VDUs are maintained by the Sponsor. Printer is maintained by the IT department. FT-IR System hardware: Tanhde mSapionntseonranhcaes wsuopupldliebde tmheadhearindwcoarnes.ulAtartriaonngwemitehntthsefSorposnesrvoric. ing Software: Documentation is the responsibility ofthe Sponsor. Safety TceoxhnpeosisCdueOrreeSdtHotHthhaetatsteshseetssmsmtaaetnendrtiaarpld.rohvainddelsindgeptariolcserdeugraersduinsgedthweithtoinxitchiteydoepf atrhtemetensttarmeasteuritiaabl lePOtoSFp.reIvtenist Iimn mcaesdeiatoeflya. total power failure, switch off the FT-IR and test compound generation equipment : 328 : APPENDIX A MIN 313/023622 (Methods of sample collection and analysis for POSF - continued) Summary of method validation The raw data for the method validation is located in study MIN/312. Uncertainty of POSF analysis UTgfruhoniemcdeePrlaOtilankSieynFslt.irseeOusffetwohrneeeyrnrelcpefsrlauisniopdcreii(cpdbtaerylusmtu(h<nei4cs.eS5frpr%tooaminnvst/otviher,)esbt3uowMtebireneqt:euleraesfnteshtrityethanlaetcinneveeu5pnli%akbtnrhaofrowylrennat)hgn.etdhAwCuatsaolgQibeurnaaetnirotatnmede(2tah%to3)d;McianultcseiurnflagetriEeonPncAse. : 329 : APPENDIX A MIN 313/023622 (Methods of sample collection and analysis for POSF - continued) PMRION/C3E13DU- RSETFUODRY PSOPSEFC(IPFEIRCFLSUUPOPRLOE-MOCETNATNETOSUTLHFOE NIYNLHFALLUAOTRIOIDNE)ANALYTICAL PTOhiSsFsuopbptaleinmeednftrdoemtaailisr saadmdiptiloensscoanlldecatmedenodnmtheentasbtoovethsetupdryo.cedure to be used for the FT-IR assay of DTcTohheneetacIaieAlsnssPtagrayiwvt,iaeoisnnncpsionrwretppihotaihrsriaenstdiutnhpagesptlprheaamenrtgeaenodtdfoisMtfui2opIN0nesr/ts3oae1nd42de0.0tahpmopesmen.dinmtehnetsc,oims spuoiutanbdlespfeocritfhice analysis IAP. of POSF, in air, at EFFECTIVE DATE : 18 December 2001 Analytical standard Name BPEuxarpticithryynduamteber Supplier FX-8B, POSF, T-7661.1, Perfluoro-octane sulfonyl fluoride N>049o05t2.5S2%u7pp(lPieedrfluoroalkyl sulfonylfluorides <4.5%) Sponsor Fourier Transform - Infrared Spectrophotometer The analysis is performed using a FT-IR analyser supplied by the sponsor. Preparation of standard solutions Prepare gasbags in the range 20 to 400 ppm. Calibration and Quantification =Cgua2ildi0be2rl0iantpieposmnfoorf tgh2ee%nep)ra.atthQinleugnargnettfhifeibrceyantacionenseptuhesycilntergane(tvhi)ne. n3iMtrogqeunansttiatnadtiavred l(icbyrlairnydegreNneor.aCte0dCa9t7030M87u4s(ientghyElePnAe Calibration Conversion Factor A conversion factor is to be used between nominal and analyser concentrations. Gasbag conc (ppm) = (AutoQuant Conc (ppm) - 8.2414)/ 1.2219 R2= 0.9995 : 330 : APPENDIX A MIN 313/023622 (Methods of sample collection and analysis for POSF - continued) EFFECTIVE DATE : 17 January 2002 Calibration and Quantification 2Cg0ua0ildi0beprlpiantmieosnfoor2fg%the)ne.eprQaattuihnalgnentrigfeitfchearbteiynocnaenusspeietnhcgytrlaethn(eev).i3nMnitqrougaenntitsattaivnedarlidbr(acryylingdeenreNraote.d97a0t153M99 (uestihnygleEnePA= : 331 : APPENDIX B Individual POSF concentration measurements MIN 313/023622 Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 1 1 35.90 92.55 69.28 2 38.33 113.27 315.96 3 36.15 115.69 331.68 4 33.10 113.96 335.12 5 34.54 113.89 332.97 6 33.79 113.48 327.27 7 34.49 113.72 318.74 8 33.98 113.53 321.30 9 34.64 113.90 324.21 10 34.86 115.03 330.44 11 34.16 115.18 331.42 12 34.81 115.07 329.33 Mean 6 34.80 114.25 327.13 sd 1.396 0.833 6.249 CV (%) 4.0 0.7 1.9 The initial concentration measurement of each exposure was excluded sd fSrtoamndaalrldcdaelcvuialatitoionns CV (%) Coefficient of variation (sd x 100/mean) 332 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 2 13 7 31.68 90.80 54.20 14 7 33.01 100.55 8.95 Mean 32.34 95.68 31.57 15 7 35.15 117.75 299.11 16 7 35.74 119.89 321.14 Mean 35.44 118.82 310.13 17 7 36.03 122.00 360.78 18 7 36.54 121.99 364.65 Mean 36.28 121.99 362.71 19 33.57 121.54 365.83 20 31.83 116.18 352.78 21 32.40 116.61 347.51 22 33.44 116.50 352.83 23 32.46 115.05 356.40 24 32.46 115.36 348.13 25 32.77 116.04 345.75 26 33.17 116.84 351.15 27 32.77 115.55 353.97 28 33.17 29 33.48 Mean 8 33.33 117.32 349.74 sd 1.573 2.416 14.502 CV (%) 4.7 2.1 4.1 8~ T Sampling time selected at 5 rather than every 10 minutes intervals The initial 2 concentration measurement of each exposure were excluded from all calculations sd Standard deviation CV (%) Coefficient of variation (sd x 100/mean) 333 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 3 30 34.90 130.74 16.23 31 38.33 142.20 48.93 32 35.32 145.53 52.30 33 36.18 138.76 341.38 34 34.32 135.83 374.05 35 36.67 131.15 378.02 36 36.51 127.34 371.22 37 35.28 126.71 352.88 38 36.56 127.23 352.70 39 37.92 126.06 350.11 40 35.80 125.75 348.27 41 37.45 128.14 352.90 Mean 6 36.39 132.25 302.07 sd 1.201 7.136 124.866 CV (%) 3.3 5.4 41.3 7 42 -0.33 9 -0.30 9 -0.32 9 43 40.82 143.55 349.91 44 40.67 146.12 388.24 45 42.73 146.27 397.31 46 41.54 146.87 402.32 47 42.35 146.42 402.25 48 41.53 150.84 400.80 49 43.12 148.34 396.29 50 40.08 147.35 394.59 51 43.16 147.42 395.53 52 43.37 146.53 395.09 53 44.45 148.59 396.89 Mean 6 42.16 147.12 392.66 sd 1.347 1.817 14.728 CV (%) 3.2 1.2 3.8 The initial concentration measurement of each exposure was excluded 9 from all calculations Chamber sample lines not connect to chamber CsdV (%) CStoaenfdfaicridendtevoifavtiaorniation (sd x 100/mean) : 334 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 8 54 122.93 10 55 140.34 10 56 154.99 10 57 170.37 10 58 183.67 10 59 195.64 10 60 25.27 105.90 207.48 10 61 24.07 126.02 357.72 62 23.24 129.13 372.61 63 21.57 127.61 372.90 64 21.78 124.02 361.56 65 22.61 126.55 359.06 66 20.66 126.59 361.39 67 20.32 124.14 359.34 68 22.93 126.77 360.38 69 23.31 128.38 360.28 70 23.59 a 126.39 362.33 71 22.09 a 128.83 362.78 Mean 22.33 a 126.77 6 362.76 sd 1.213 1.682 5.156 CV (%) 5.4 1.3 1.4 The initial concentration measurement of each exposure was excluded from all calculations 10 Sampling time selected at 1 rather than every 10 minutes intervals, values excluded from mean and standard deviation sd Standard deviation CV (%) Coefficient of variation (sd x 100/mean) a Overall mean is time weighted for samples 70 and 71. The mean of these two samples is used in the overall caluclations. : 335 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 10 72 73 1191.86 9151.85 69.43 330.27 74 20.67 131.48 360.69 75 20.38 130.55 360.93 76 21.51 129.94 360.96 77 21.19 128.79 359.95 78 20.36 129.67 358.44 79 21.52 129.41 356.23 80 21.89 129.40 358.68 81 22.36 130.69 361.78 82 21.04 132.40 372.17 83 23.19 129.88 365.15 Mean 6 21.41 130.22 358.66 sd 0.896 1.083 10.307 CV (%) 4.2 0.8 2.9 The initial concentration measurement of each exposure was excluded from all calculations 11 Computer malfunction with data capture programme during exposure as it was observed that the backup drive was full. Rectified by changing to fresh zip disk. sd Standard deviation CV (%) Coefficient of variation (sd x 100/mean) 336 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 11 84 39.60 137.85 256.25 85 40.91 154.56 336.79 86 40.87 159.78 377.66 87 41.67 163.38 385.94 88 40.74 163.10 387.87 89 42.12 165.72 388.93 90 40.52 164.94 392.01 91 42.29 152.18 389.73 92 40.79 124.65 396.41 93 40.23 125.31 405.70 94 41.44 124.03 363.92 95 41.11 123.08 356.98 Mean 6 41.15 147.34 380.17 sd 0.654 18.751 20.016 CV (%) 1.6 12 96 39.05 12.7 84.53 152.3 97 41.78 128.93 325.45 98 40.74 133.38 362.16 99 41.44 133.81 378.47 100 40.44 133.96 380.42 101 41.09 132.09 376.41 102 41.05 132.16 376.09 103 40.69 131.55 375.12 104 41.00 129.85 370.99 105 41.69 130.53 372.55 106 41.56 133.59 373.38 107 40.82 131.64 373.78 Mean 6 41.12 131.95 369.53 sd 0.443 1.676 15.366 CV (%) 1.1 1.3 4.2 The initial concentration measurement of each exposure was excluded 12 from all calculations Sample missed as analysis started late in error CsdV (%) CStoaenfdfaicridendtevoifavtiaorniation (sd x 100/mean) : 337 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 13 108 39.94 97.15 136.85 109 43.16 116.79 328.28 110 42.73 120.36 354.56 111 41.84 120.12 356.49 112 42.95 126.85 352.76 113 43.39 141.33 380.05 114 43.15 141.21 379.63 115 43.68 137.95 379.08 116 43.10 136.71 380.39 117 43.23 136.76 380.04 118 43.62 137.16 383.01 119 44.16 140.35 381.80 Mean 6 43.18 132.33 368.73 sd 0.593 9.391 17.985 CV (%) 1.4 7.1 4.9 14 120 3.44 2.84 4.53 121 20.56 19.96 327.08 122 45.85 131.04 373.76 123 44.88 134.56 365.24 124 44.18 131.30 366.61 125 44.52 134.09 364.23 126 43.48 135.35 364.13 127 44.03 136.22 368.66 128 43.89 135.93 369.21 129 45.40 134.68 370.31 130 44.82 134.65 371.43 131 44.12 136.03 373.60 Mean 6 42.34 123.98 364.93 sd 7.257 34.546 13.011 CV (%) 17.1 27.9 3.6 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 338 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 15 132 6.20 13 113.67 311.48 133 12.34 13 137.61 367.35 134 6.86 13 143.16 382.52 135 35.91 143.10 388.48 136 41.80 139.85 383.03 137 40.23 141.18 383.36 138 41.76 140.74 378.17 139 42.35 137.69 375.66 140 41.35 139.23 375.23 141 41.35 139.32 374.48 142 43.37 141.19 376.17 143 42.17 140.46 375.38 Mean 6 35.41 140.32 378.16 sd 12.961 1.846 5.773 CV (%) 36.6 1.3 1.5 16 144 44.73 119.42 109.02 145 46.44 143.35 367.09 146 45.40 145.90 400.96 147 45.09 146.04 392.96 148 46.21 145.41 390.15 149 45.12 144.29 385.77 150 45.94 144.94 387.23 151 45.66 146.25 388.61 152 46.20 146.21 389.78 153 46.57 146.55 394.96 154 46.87 146.89 398.52 155 47.96 146.32 399.36 Mean 6 46.13 145.65 390.49 sd 0.843 1.066 9.293 CV (%) 1.8 0.7 2.4 The initial concentration measurement of each exposure was excluded from all calculations 13 Syringe driver incorrectly set at start of exposure CsdV (%) CStoaenfdfaicridendtevoifavtiaorniation (sd x 100/mean) : 339 : MIN 313/023622 APPENDIX B (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 17 156 42.98 115.04 133.52 157 43.48 122.76 349.23 158 44.37 123.47 368.05 159 44.15 119.40 365.70 160 44.63 120.33 365.13 161 44.42 121.94 371.88 162 44.01 122.91 383.05 163 45.88 121.80 384.45 164 44.88 119.55 384.35 165 45.25 124.05 386.08 166 45.26 128.18 388.02 167 46.34 128.27 389.64 Mean 6 44.79 122.97 375.96 sd 0.843 3.010 12.822 CV (%) 1.9 2.4 3.4 18 168 40.04 104.86 218.39 169 40.50 120.73 347.40 170 40.74 122.04 366.15 171 41.78 122.67 365.99 172 42.08 124.61 369.35 173 42.57 125.99 365.23 174 42.12 126.21 363.72 175 42.47 126.93 361.94 176 42.87 125.19 368.71 177 42.77 126.88 385.43 178 42.90 127.85 393.29 179 42.80 129.60 398.75 Mean 6 42.15 125.34 371.45 sd 0.838 2.653 15.016 CV (%) 2.0 2.1 4.0 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 340 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 19 180 14 181 14 182 43.31 125.29 399.81 183 42.40 125.64 411.94 184 43.09 124.45 380.88 185 43.47 120.64 373.43 186 44.93 123.18 366.86 187 42.31 124.02 363.96 188 41.39 123.33 364.05 189 43.58 125.47 378.18 190 43.62 126.77 386.73 191 43.55 126.59 388.45 Mean 6 43.165 124.54 381.43 sd 0.9569 1.84 15.78 CV (%) 2.2 1.5 4.1 20 192 2.24 100.04 84.58 193 73.48 123.30 352.36 194 39.57 126.59 387.60 195 39.90 125.30 391.28 196 38.44 125.42 389.29 197 41.29 124.10 382.83 198 40.64 123.95 371.92 199 41.51 123.55 370.23 200 41.18 123.75 369.34 201 41.38 125.30 373.65 202 42.59 131.93 375.02 203 41.47 130.40 374.77 Mean 6 43.77 125.78 376.21 sd 9.918 2.861 11.188 CV (%) 22.7 2.3 3.0 The initial concentration measurement of each exposure was excluded fTriomme-aclolnctarlocullleadtiocnhsamber switching device out of synchrony with mmeeaasnuarnemd esntatn, dsaarmdpdleevciaotliloencted over 2 groups, values excluded from CsdV (%) CStoaenfdfaicridendtevoifavtiaorniation (sd x 100/mean) : 341 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 21 204 36.69 94.76 83.95 205 38.54 113.61 312.36 206 39.89 117.11 352.13 207 39.70 115.33 355.36 208 38.95 113.83 366.07 209 39.28 113.43 335.20 210 38.37 115.61 318.35 211 40.59 119.13 362.39 212 40.56 119.31 373.52 213 40.59 119.82 372.14 214 40.20 120.53 373.54 215 40.06 121.05 372.45 Mean 6 39.70 117.16 353.96 sd 0.811 2.924 22.389 CV (%) 2.0 2.5 6.3 22 216 39.30 100.58 114.06 217 39.86 117.88 354.92 218 39.74 120.56 376.31 219 40.10 117.48 385.68 220 39.06 117.83 386.24 221 38.69 120.75 382.81 222 39.69 121.86 391.60 223 39.89 119.89 390.29 224 38.67 119.04 392.70 225 40.16 119.18 391.00 226 39.98 120.02 390.68 227 41.64 124.38 391.23 Mean 6 39.77 119.90 384.86 sd 0.820 2.012 11.067 CV (%) 2.1 1.7 2.9 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 342 : MIN 313/023622 APPENDIX B (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 23 228 41.70 102.53 257.45 229 42.14 126.01 367.43 230 40.26 129.21 400.37 231 40.89 129.67 409.41 232 41.22 128.41 396.45 233 41.75 127.74 380.48 234 40.95 126.51 382.36 235 43.11 126.68 380.13 236 41.91 129.06 384.69 237 42.68 131.20 383.94 238 43.15 131.09 382.87 239 42.81 130.97 382.97 Mean 6 41.90 128.78 386.46 sd 0.980 1.885 11.444 CV (%) 2.3 1.5 3.0 24 240 59.85 129.61 148.70 241 63.11 147.22 375.61 242 60.23 149.54 407.34 243 61.31 141.12 400.47 244 57.70 142.37 393.96 245 56.57 143.23 391.62 246 56.28 144.13 391.74 247 57.35 144.86 392.28 248 54.99 139.36 391.70 249 56.08 140.61 392.38 250 56.06 143.21 394.66 251 56.62 141.56 393.35 Mean 6 57.84 143.38 393.19 sd 2.564 2.979 7.571 CV (%) 4.4 2.1 1.9 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 343 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 25 252 30.84 111.70 93.22 253 33.23 119.18 334.79 254 38.65 119.84 363.66 255 37.64 120.48 366.52 256 36.95 120.98 366.55 257 38.55 118.42 365.26 258 40.24 117.84 366.08 259 39.18 126.60 366.96 260 39.10 127.90 367.12 261 38.92 125.76 366.40 262 39.85 126.45 366.91 263 40.73 126.59 369.85 Mean 6 38.46 122.73 363.65 sd 2.042 3.889 9.682 CV (%) 5.3 3.2 2.7 26 264 38.73 105.65 124.48 265 39.50 132.68 345.22 266 40.62 136.33 368.37 267 40.64 131.73 367.59 268 40.73 131.68 367.15 269 40.55 136.58 366.16 270 39.82 137.20 366.56 271 40.78 134.76 365.63 272 40.56 135.74 366.14 273 42.63 135.96 365.94 274 41.33 135.94 369.44 275 41.16 137.71 369.57 Mean 6 40.76 135.12 365.25 sd 0.811 2.141 6.783 CV (%) 2.0 1.6 1.9 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 344 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 27 276 40.18 108.26 97.60 277 40.31 132.81 333.61 278 41.30 138.52 365.51 279 39.56 136.87 374.62 280 41.24 136.02 368.45 281 39.65 134.74 364.71 282 40.44 134.80 361.69 283 40.80 135.44 360.84 284 41.21 135.77 362.29 285 40.63 136.42 365.36 286 42.95 137.09 365.96 287 40.85 137.40 370.96 Mean 6 40.81 135.99 363.09 sd 0.921 1.549 10.595 CV (%) 2.3 1.1 2.9 28 288 40.18 115.18 101.56 289 41.78 129.92 366.93 290 42.11 131.01 375.46 291 41.62 134.33 375.24 292 40.15 133.65 373.83 293 42.80 132.06 373.03 294 41.20 131.52 371.78 295 42.68 132.97 368.54 296 42.44 133.71 375.67 297 42.83 133.86 372.59 298 41.49 133.42 376.12 299 42.72 132.04 375.06 Mean 6 41.98 132.59 373.11 sd 0.838 1.384 3.019 CV (%) 2.0 1.0 0.8 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 345 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 29 300 39.00 115.96 281.48 301 40.30 142.70 357.92 302 42.39 141.69 383.39 303 41.40 131.70 381.43 304 41.20 130.98 378.05 305 41.57 131.07 376.59 306 41.58 132.06 378.17 307 42.10 132.38 379.36 308 41.65 131.68 383.07 309 41.24 131.67 378.66 310 42.51 132.17 379.34 311 43.69 136.46 384.56 Mean 6 41.79 134.05 378.23 sd 0.878 4.294 7.200 CV (%) 2.1 3.2 1.9 30 312 43.08 110.18 104.51 313 44.88 127.62 342.01 314 44.00 141.97 370.71 315 43.32 140.98 385.94 316 43.83 138.47 373.85 317 44.23 137.21 368.95 318 44.47 136.18 369.93 319 44.62 135.88 370.89 320 45.41 136.86 373.25 321 43.72 137.36 376.54 322 44.19 135.71 374.70 323 43.94 138.59 377.14 Mean 6 44.24 136.98 371.26 sd 0.584 3.702 10.786 CV (%) 1.3 2.7 2.9 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 346 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 31 324 41.23 122.56 92.77 325 41.38 138.49 348.71 326 41.93 136.16 389.29 327 41.36 141.71 391.07 328 41.99 140.66 376.82 329 40.85 140.85 377.81 330 40.98 140.13 379.77 331 41.25 134.52 384.00 332 39.97 140.82 385.50 333 41.59 142.92 386.36 334 42.10 141.63 386.60 335 42.54 141.35 390.94 Mean 6 41.45 139.93 381.53 sd 0.705 2.545 11.945 CV (%) 1.7 1.8 3.1 32 336 36.89 108.07 68.97 337 38.14 128.15 328.86 338 38.61 135.52 366.71 339 37.62 134.33 369.47 340 38.01 134.73 370.31 341 38.61 133.52 368.87 342 39.18 135.24 372.46 343 40.90 137.13 375.19 344 39.06 137.00 377.62 345 40.52 136.98 373.86 346 40.64 136.77 373.68 347 41.64 139.90 375.60 Mean 6 39.36 135.39 368.42 sd 1.346 2.964 13.520 CV (%) 3.4 2.2 3.7 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 347 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 33 348 37.69 115.51 77.87 349 39.83 137.08 345.41 350 40.32 139.17 372.03 351 40.59 137.72 374.35 352 40.12 136.18 372.51 353 40.27 136.20 372.40 354 40.74 136.92 370.83 355 40.80 137.86 372.19 356 39.09 139.94 373.02 357 41.54 142.87 373.66 358 40.55 140.10 375.38 359 41.44 139.56 376.69 Mean 6 40.48 138.51 370.77 sd 0.692 2.037 8.573 CV (%) 1.7 1.5 2.3 35 360 39.81 109.35 61.78 361 40.82 134.10 346.78 362 40.84 137.26 388.17 363 40.35 136.13 389.64 364 40.97 134.37 387.76 365 39.86 134.03 388.65 366 40.84 134.33 390.82 367 42.11 134.26 391.30 368 40.22 134.44 392.30 369 41.71 135.68 392.48 370 41.34 135.37 391.04 371 39.74 137.57 393.68 Mean 40.80 135.23 386.60 sd 0.736 1.283 13.340 CV (%) 1.8 0.9 3.45 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 348 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 36 372 38.42 121.10 202.70 373 39.23 131.97 367.10 374 39.40 134.49 389.06 375 38.78 133.54 375.05 376 38.41 131.27 366.55 377 39.38 132.75 363.17 378 39.31 135.10 364.81 379 39.99 134.92 361.86 380 38.81 134.00 364.23 381 39.83 135.03 368.88 382 40.83 134.50 369.28 383 40.13 136.51 370.27 Mean 6 39.46 134.01 369.11 sd 0.693 1.524 7.585 CV (%) 1.8 1.1 2.1 37 384 37.17 115.55 119.43 385 39.19 140.86 354.04 386 38.78 142.03 379.80 387 40.23 139.28 382.51 388 39.56 133.42 386.25 389 40.25 132.33 388.03 390 39.41 131.81 386.03 391 39.50 131.66 384.07 392 40.19 132.59 384.71 393 40.06 132.90 380.54 394 39.51 131.69 389.82 395 40.24 128.53 390.12 Mean 6 39.72 134.28 382.36 sd 0.503 4.365 9.985 CV (%) 1.3 3.3 2.6 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 349 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 38 396 44.26 103.94 134.80 397 41.71 133.83 370.04 398 40.52 134.46 392.60 399 42.41 136.21 392.35 400 41.58 138.35 391.19 401 41.22 137.96 390.95 402 41.68 136.82 386.97 403 42.30 134.46 386.02 404 41.45 135.47 387.15 405 43.00 135.72 388.95 406 42.56 140.81 394.32 407 43.64 138.35 394.35 Mean 6 42.01 136.59 388.63 sd 0.880 2.117 6.812 CV (%) 2.1 1.6 1.8 39 408 347.10 129.38 277.10 409 20.65 146.13 388.04 410 46.79 145.34 396.02 411 43.03 147.11 394.47 412 43.13 146.81 396.60 413 42.12 144.46 397.08 414 42.59 143.14 396.75 415 42.69 145.55 398.55 416 43.79 145.91 400.86 417 43.48 146.06 396.23 418 43.62 147.08 395.93 419 44.12 145.97 394.04 Mean 6 41.45 145.78 395.87 sd 7.009 1.172 3.188 CV (%) 16.9 0.8 0.8 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 350 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 40 420 41.39 111.51 97.23 421 43.16 135.88 363.21 422 42.89 137.89 383.43 423 42.40 138.52 386.36 424 41.55 138.76 381.98 425 41.44 137.60 382.03 426 42.75 136.32 385.98 427 42.51 137.54 391.57 428 41.52 138.38 391.55 429 41.76 136.37 391.40 430 42.76 135.97 390.97 431 42.64 136.10 393.04 Mean 6 42.31 137.21 385.59 sd 0.623 1.107 8.494 CV (%) 1.5 0.8 2.2 41 432 36.22 117.90 126.18 433 36.20 134.74 344.49 434 36.78 131.04 352.89 435 37.02 125.50 353.18 436 36.96 124.69 349.02 437 37.41 125.96 348.81 438 37.55 126.35 350.20 439 37.37 125.59 353.12 440 37.67 127.02 352.55 441 37.42 123.69 355.82 442 38.67 123.88 357.96 443 38.26 124.90 353.65 Mean 6 37.39 126.67 351.97 sd 0.678 3.335 3.677 CV (%) 1.8 2.6 1.0 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 351 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 42 444 37.02 107.71 125.72 445 38.49 135.89 282.30 446 37.64 136.10 322.67 447 38.62 135.68 343.65 448 37.21 133.49 348.74 449 37.87 133.24 350.07 450 38.95 133.32 351.09 451 37.89 133.96 351.22 452 39.01 133.02 352.05 453 38.78 132.47 352.13 454 37.62 135.38 352.32 455 40.63 135.89 350.37 Mean 6 38.43 134.40 341.51 sd 0.947 1.382 21.440 CV (%) 2.5 1.0 6.3 43 456 15 457 41.81 138.78 336.91 458 41.33 141.36 360.84 459 40.76 139.00 366.44 460 41.56 138.38 367.70 461 41.87 136.97 366.83 462 40.36 137.62 368.55 463 41.50 139.47 369.00 464 41.00 138.79 365.29 465 42.38 137.28 368.64 466 41.84 137.45 369.23 467 41.40 141.33 374.68 Mean 6 41.44 138.766 364.92 sd 0.5670 1.4997 9.862 CV (%) 1.4 1.1 2.7 The initial concentration measurement of each exposure was excluded 15 fCroommpaultlecramlcuallfautinocntsion with data capture programme during exposure CsdV (%) CStoaenfdfaicridendtevoifavtiaorniation (sd x 100/mean) : 352 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 44 468 36.25 107.61 17 145.81 17 469 36.70 144.64 355.78 470 35.19 135.31 366.72 471 34.72 132.79 358.87 472 35.57 131.69 357.86 473 36.14 109.64 355.45 474 35.39 134.55 353.91 475 35.32 130.04 355.31 476 35.55 130.18 355.81 477 37.15 132.07 359.99 478 35.29 129.76 362.08 479 36.42 131.71 363.46 Mean 6 35.77 131.12 358.66 sd 0.736 8.257 4.031 CV (%) 2.1 45 480 36.88 6.3 98.70 116.1 481 40.03 137.29 324.31 482 39.54 139.74 348.06 483 39.37 140.54 360.02 484 39.65 137.62 363.46 485 38.64 136.34 363.59 486 40.13 135.74 364.67 487 39.69 134.98 362.17 488 40.15 136.73 360.70 489 39.26 137.75 360.69 490 40.05 138.59 362.70 491 138.63 364.80 Mean 6 39.65 137.63 357.74 sd 0.477 1.674 12.013 CV (%) 1.2 1.2 3.4 The initial concentration measurement of each exposure was excluded 16 from all calculations Computer data capture programme froze and had to be reset during 17 Eextphoysleunree in nitrogen calibration cylinder left on in error CsdV (%) CStoaenfdfaicridendtevoifavtiaorniation (sd x 100/mean) : 353 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 46 492 37.72 113.77 108.27 493 39.69 137.02 335.70 494 40.60 138.54 358.72 495 39.79 139.06 366.89 496 38.88 138.06 363.84 497 39.64 137.87 358.95 498 40.23 137.10 364.08 499 40.44 136.43 357.23 500 41.44 141.63 361.55 501 41.22 140.92 364.44 502 40.23 137.49 365.50 503 42.03 139.07 365.07 Mean 6 40.38 138.47 360.18 sd 0.909 1.623 8.702 CV (%) 2.3 1.2 2.4 47 504 12 505 12 506 12 507 40.09 12 12 508 38.95 148.33 362.91 509 38.96 145.82 360.01 510 39.78 145.92 360.67 511 39.88 146.64 360.14 512 41.46 143.04 361.02 513 39.69 132.86 362.21 514 40.19 132.01 365.13 515 41.83 132.85 367.19 Mean 6 40.09 140.93 362.41 sd 0.987 7.080 2.574 CV (%) 2.5 5.0 0.7 The initial concentration measurement of each exposure was excluded 12 from all calculations Sample missed as analysis started late in error CsdV (%) CStoaenfdfaicridendtevoifavtiaorniation (sd x 100/mean) : 354 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 48 516 36.02 113.08 255.13 517 38.58 133.51 343.18 518 39.46 127.63 363.12 519 38.90 127.44 368.26 520 38.48 126.95 364.47 521 38.91 127.01 363.93 522 38.79 124.13 364.28 523 38.81 123.50 363.67 524 39.70 122.26 365.28 525 39.06 135.84 366.73 526 39.70 134.99 367.04 527 40.26 134.75 369.94 Mean 6 39.15 128.91 363.63 sd 0.554 4.978 7.104 CV (%) 1.4 3.9 3.0 49 528 35.70 109.84 73.51 529 37.44 137.12 341.36 530 37.02 139.57 364.71 531 37.60 145.98 368.11 532 36.94 132.51 359.55 533 37.14 129.64 357.14 534 36.85 129.81 355.17 535 36.53 129.62 353.37 536 36.40 129.72 353.83 537 36.22 126.62 353.95 538 37.24 128.04 356.18 539 37.33 129.82 359.01 Mean 6 36.97 132.59 356.58 sd 0.442 5.883 6.876 CV (%) 1.2 4.4 1.9 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 355 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 50 540 25.70 103.22 76.33 541 34.77 130.73 311.87 542 35.63 132.81 349.47 543 35.45 133.29 356.10 544 35.94 133.02 355.08 545 37.44 135.13 366.75 546 37.18 137.08 382.49 547 37.71 137.89 381.77 548 37.58 140.14 381.62 549 36.88 140.41 380.89 550 38.17 137.22 382.62 551 38.22 137.31 384.60 Mean 6 36.82 135.91 366.66 sd 1.182 3.153 22.416 CV (%) 3.2 2.3 6.1 51 552 36.73 116.01 89.34 553 38.71 139.96 341.25 554 39.35 142.41 372.60 555 40.23 141.92 373.48 556 40.70 142.66 373.62 557 38.50 141.13 376.43 558 38.09 138.42 377.82 559 39.69 138.61 377.28 560 38.78 138.92 376.47 561 39.86 140.44 375.90 562 40.12 142.80 381.29 563 40.53 142.62 383.57 Mean 6 39.50 140.90 373.61 sd 0.880 1.715 11.222 CV (%) 2.2 1.2 3.0 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 356 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 52 564 38.83 105.46 93.48 565 40.88 142.00 346.87 566 40.56 146.12 373.05 567 40.98 144.98 375.68 568 41.17 141.01 373.27 569 41.09 140.11 372.69 570 42.30 141.28 377.88 571 42.40 143.43 378.45 572 40.86 143.93 375.85 573 42.72 138.33 378.21 574 41.38 136.85 376.73 575 43.14 138.80 376.45 Mean 6 41.59 141.53 373.19 sd 0.882 2.907 8.969 CV (%) 2.1 2.1 2.4 53 576 35.26 113.40 92.75 577 37.08 142.41 377.63 578 38.99 144.11 408.97 579 38.23 143.50 410.05 580 39.95 143.36 407.35 581 40.81 147.78 417.63 582 39.91 155.81 430.02 583 38.98 151.08 408.38 584 39.76 147.26 398.82 585 39.06 147.63 396.67 586 40.11 142.01 395.94 587 45.38 145.88 399.94 Mean 6 39.84 146.44 404.67 sd 2.098 4.160 13.442 CV (%) 5.3 2.8 3.3 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 357 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 54 588 38.13 108.39 103.62 589 39.75 142.78 358.22 590 38.79 144.35 415.38 591 40.57 145.69 385.58 592 38.72 145.68 369.73 593 40.02 145.58 376.46 594 39.97 145.09 380.00 595 39.40 144.00 378.43 596 39.93 142.50 378.03 597 38.82 140.85 377.80 598 39.12 141.39 379.55 599 43.01 141.63 381.31 Mean 6 39.83 143.59 380.04 sd 1.214 1.837 13.741 CV (%) 3.0 1.3 3.6 55 600 37.27 102.05 69.33 601 37.33 136.20 330.48 602 37.05 138.89 364.23 603 37.99 139.47 371.75 604 38.31 140.36 377.64 605 39.54 139.40 375.53 606 38.23 140.17 375.46 607 38.13 141.19 377.60 608 38.59 142.20 386.92 609 38.65 141.83 387.09 610 40.42 141.61 382.42 611 40.19 142.25 381.92 Mean 6 38.59 140.32 373.73 sd 1.075 1.804 15.800 CV (%) 2.8 1.3 4.2 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 358 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 56 612 38.10 -0.45 90.59 613 37.74 137.57 341.84 614 40.23 140.48 369.75 615 40.20 140.21 378.04 616 40.23 141.45 379.22 617 40.15 144.40 382.88 618 40.33 142.69 379.52 619 39.91 142.89 381.79 620 37.99 144.07 389.34 621 37.83 146.34 389.20 622 39.07 143.92 388.07 623 40.50 142.01 382.02 Mean 6 39.47 142.37 378.33 sd 1.104 2.406 13.373 CV (%) 2.8 57 624 39.14 112.7 132.5 625 41.83 138.91 251.89 626 41.51 145.30 371.68 627 41.29 145.89 383.20 628 41.21 145.38 384.95 629 41.44 145.61 379.96 630 42.60 144.44 381.84 631 42.71 144.64 377.96 632 43.03 145.48 384.94 633 42.95 145.08 384.45 634 43.30 147.40 383.69 635 43.75 148.50 391.78 Mean 6 42.33 145.15 370.58 sd 0.899 2.387 39.677 CV (%) 2.1 1.6 10.7 The initial concentration measurement of each exposure was excluded 12 from all calculations Sample missed as analysis started late in error CsdV (%) CStoaenfdfaicridendtevoifavtiaorniation (sd x 100/mean) : 359 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 58 636 39.83 118.41 122.15 637 41.89 150.19 299.12 638 42.16 149.20 344.73 639 40.62 133.72 378.10 640 40.14 133.32 383.34 641 41.40 133.80 388.67 642 42.32 138.04 388.85 643 41.26 146.13 388.29 644 41.27 150.60 391.02 645 41.92 134.84 390.22 646 41.05 131.03 385.96 647 42.22 127.41 384.83 Mean 6 41.48 138.93 374.83 sd 0.699 8.473 28.307 CV (%) 1.7 6.1 7.6 59 648 0.20 18 116.68 204.63 649 0.23 18 138.55 304.27 650 35.04 139.96 367.38 651 38.84 142.17 384.71 652 38.92 138.00 388.95 653 40.03 138.72 393.51 654 39.44 139.79 394.78 655 39.56 140.69 393.48 656 40.41 140.26 393.38 657 40.82 139.95 394.27 658 41.06 140.91 395.97 659 44.51 142.54 397.84 Mean 6 36.26 140.14 382.59 sd 12.155 1.418 27.317 CV (%) 33.5 1.0 7.1 The initial concentration measurement of each exposure was excluded 18 from all calculations Low concentration due to air bubble in test material feed line CsdV (%) CStoaenfdfaicridendtevoifavtiaorniation (sd x 100/mean) : 360 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 60 660 -0.33 110.62 160.67 661 37.53 139.46 363.69 662 38.13 143.48 381.80 663 37.31 144.36 389.25 664 37.06 145.10 397.01 665 38.85 145.11 393.56 666 39.29 145.18 394.04 667 39.66 145.25 394.12 668 39.28 145.54 398.33 669 39.04 147.20 402.95 670 41.29 146.10 402.39 671 39.87 144.33 402.71 Mean 6 38.85 144.65 392.71 sd 1.262 1.973 11.516 CV (%) 3.2 1.4 2.9 The initial concentration measurement of each exposure was excluded sd fSrtoamndaalrldcdaelcvuialatitoionn. s CV (%) Coefficient of variation (sd x 100/mean) 361 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 61 672 10 96.65 673 10 115.11 674 10 675 14 13124.16 676 10 80.00 677 10 85.09 678 10 89.69 679 10 94.05 680 10 97.80 00 o 101.53 682 10 105.34 683 10 109.05 684 10 112.31 685 10 686 14 11154.67 687 10 45.88 688 10 45.57 689 10 45.52 690 10 45.88 691 10 46.14 692 10 46.31 693 50.15 147.87 424.28 694 51.61 153.81 427.93 695 50.72 145.76 432.32 696 47.25 145.89 428.16 697 45.23 145.52 424.75 698 44.55 145.23 411.27 699 45.70 145.42 419.83 700 45.38 146.25 414.58 701 45.76 148.07 417.72 702 46.93 148.20 420.21 703 49.61 148.50 Mean 47.53 147.32 422.10 sd 2.524 2.489 6.572 CV (%) 5.3 1.7 1.6 14 sCdV (%) TfCSScrotiaooamlmmelnefepdfc-mlaicticernoeiddegnandtnorttevoiavomelnilrfaeedv2tdiassogtrceanirhlanoeatducimoatpernbsdd,e(vrdsaadestlwvux1ieiats1rtcai0hoet0ihxnn/cemglruedtdaheneavd)nicfereovomeurtymoe1fa0snymnacninhdursottenasyndiwnatiretdhrvdmaelves.aiastVuioraenlmueesnte,xscalmudpelde : 362 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 62 704 -0.23 -0.20 -0.16 705 43.64 134.40 126.87 706 43.49 139.92 394.16 707 43.36 139.84 403.15 708 43.18 137.71 400.62 709 44.21 137.89 403.42 710 43.90 137.15 403.90 711 43.74 137.05 403.34 712 44.65 138.31 402.69 713 45.58 138.15 403.90 714 46.69 138.65 406.52 715 40.82 138.14 405.98 Mean 6 43.93 137.93 377.69 sd 1.476 1.492 83.252 CV (%) 3.4 1.1 22.0 63 716 43.60 109.48 109.10 717 44.85 137.25 380.19 718 44.89 139.46 410.27 719 46.28 139.66 413.29 720 44.72 142.53 413.02 721 45.82 142.64 417.57 722 45.53 141.35 416.17 723 46.09 141.43 415.58 724 47.00 142.30 418.35 725 47.66 141.87 417.52 726 48.91 141.99 417.82 727 17.15 142.20 420.97 Mean 6 43.54 141.15 412.80 sd 8.844 1.679 11.212 CV (%) 20.3 1.2 2.7 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 363 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 (Low dose) (Inter. dose) (High dose) 64 728 45.20 101.07 20.79 729 46.15 137.11 347.32 730 47.13 139.70 418.78 731 47.31 139.65 426.18 732 46.47 139.91 423.25 733 46.52 138.04 414.69 734 47.01 138.84 414.02 735 46.80 136.37 414.42 736 45.43 144.27 414.72 737 44.30 136.13 413.70 738 45.88 136.52 414.75 739 47.13 135.42 416.88 Mean 6 46.37 138.36 410.79 sd 0.900 2.524 21.447 CV (%) 1.9 1.8 5.2 65 740 40.07 117.10 75.70 741 40.60 136.15 366.40 742 42.38 137.77 400.42 743 42.33 137.77 412.38 744 42.55 137.85 411.73 745 42.95 137.36 409.56 746 43.11 137.60 406.32 747 42.40 139.11 408.85 748 44.71 139.46 408.09 749 44.21 135.51 413.05 750 46.10 135.55 414.21 751 37.61 137.77 415.27 Mean 6 42.63 137.44 406.02 sd 2.208 1.277 13.789 CV (%) 5.2 0.9 3.4 The initial concentration measurement of each exposure was excluded CsdV (%) SCfrtooaemnfdfaaiclrlidecndatelcvouifalavtitaoironina.stion (sd x 100/mean) : 364 : APPENDIX B MIN 313/023622 (Individual POSF concentration measurements - continued) Exposure Sample Chamber Concentration (ppm) No. No. Group 2 Group 3 Group 4 66 752 (Low14dose) (Inter1.4dose) (High12dose) 753 14 754 38.76 136.70 403.38 755 41.05 136.23 406.44 756 41.64 136.44 409.08 757 41.35 138.19 411.40 758 42.10 138.76 416.98 759 41.48 138.53 415.86 760 43.32 140.80 420.91 761 42.45 139.96 421.06 762 45.29 140.23 419.66 763 46.05 140.25 425.00 Mean 42.348 138.609 414.98 sd 2.1126 1.7052 7.106 CV (%) 5.0 1.2 1.7 67 764 -0.34 103.26 52.41 765 37.28 143.26 358.26 766 38.88 145.92 403.83 767 38.47 145.82 407.26 768 39.33 145.95 404.32 769 40.29 146.00 406.00 770 40.78 144.80 407.33 771 40.35 145.49 406.13 772 41.62 146.29 406.36 773 42.18 146.92 410.03 774 41.70 146.40 411.34 756 43.57 149.24 413.76 Mean 40.40 146.01 403.15 sd 1.829 1.443 15.184 CV (%) 4.5 1.0 3.8 Sample missed as analysis started late in error Time-controlled chamber switching device out of synchrony with measurement, sample collected over 2 groups, values excluded from sd mSteaanndaarndddsetvainadtaiornd deviation CV (%) Coefficient of variation (sd x 100/mean) : 365 : PERFLUOROOCTANESULFONYL FLUORIDE (POSF; T-7661.4) TOXICITY STUDY BY INHALATION ADMINISTRATION TO CD RATS FOR 13 WEEKS FOLLOWED BY A 4 WEEK RECOVERY PERIOD Volume 2 MIN 313/023622 PERFLUOROOCTANESULFONYL FLUORIDE (POSF; T-7661.4) TOXICITY STUDY BY INHALATION ADMINISTRATION TO CD RATS FOR 13 WEEKS FOLLOWED BY A 4 WEEK RECOVERY PERIOD Volume 2 Sponsor BMU33SMMtuSNPiAlaCCd5.uieo5nln,r1gpt3eo23rr2,-a30t2e-22TE0o,-0x2ic,ology, Research Laboratory HAHPEWCENaluuocm2nnGoo8ttbnliiLlnnrb4eAigguHydddNrgSRyooeD,,nnos,.haLdiri,efe, Sciences Ltd., Report issued: 28 September 2005 Page 366 of 740 MIN 313/023622 CONTENTS Page CONTENTS......................................................................................................................................... 2 COMPLIANCE WITH GOOD LABORATORY PRACTICE...................................................... 4 QUALITY ASSURANCE STATEMENT........................................................................................ 5 CONTRIBUTING SCIENTISTS....................................................................................................... 6 SUMMARY......................................................................................................................................... 7 INTRODUCTION............................................................................................................................... 9 EXPERIMENTAL PROCEDURE..................................................................................................... NAPDTQSSAETEENAURUSCTITAMTIDRHAALYOASOILTTUPLLSRYOSBOCMEYBSAHGAATSSAEYTEANSDNMR.NUA.UD.V.CERG.L.AHNE.A.EE.TIT.NAM.SA.I..CN.OT..NE..E.DO.N.N.D...AL.S.FT....SO.N.O.......T....GD.R.....R......Y.M...A..U...........RU...C............C..L.T..........H..A..U.............IT...R...V.......I....E...O..I......N..........N.........G..........................P................R.....................O.....................C.....................E....................D......................U.....................R.....................E.....................S................................................................................................................................................................................................................................................................................................................................................................................................... 11 2221111122165392 RESULTS............................................................................................................................................. 27 DISCUSSION...................................................................................................................................... 35 REFERENCES..................................................................................................................................... 36 FIGURES 1. Bodyweights - group mean values.............................................................................................. 37 : 367 : TABLES MIN 313/023622 Page 24356781........ FBBHUMMOoioraraioiogcedcncdarmyrahonowlceasyswocmtecsoonioieligspsosiphugitg-icrtmhcysygtpppsr---aoatg-tigguthorhgrrpoonooorulmouulo-opuppgeggpmaymmryonme-eeu-avaaegpgnnnaarrmonlvovvuuuaevaaepplaallsunuudl.de.ueei.vis.ssses..at....tsr....lr.....iui.....b.b....e.....u....u.s......t....t......ii......o.o............n.n................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................ 4346758810862307 APPENDICES 24356798111.........01.. DFBHBUIpAWnCHoiorbaadoeeioedisniecllvdvomylyakhailwpllcdeualpyyuromtuteosooeenipaislligssslhitosohf-utfypgr-edrtomgsyasyroiraiantpsc-hnt-t-detaeioiioiiiwrlnovnnlomnodeniddbedgixifiiisv-unvvgiiaenciaaiihimrdddadnllvtuluuisdiavunnaaafit-argvlaiillionltsiivnvvuindndoa.eaadeus.iln..llnsiau..uu-v...lg-e...ieei...vssd..ni.ss...n..a.u..d.......d....l.a..i.....u....vi..l.......v...e....i..v.....di...s....d...a....u..........u..l.....a.....u.....a.....l........e.l...........f....s....f....i.........i.n............n.........d...........d............i.........in..........n............g.........g...........s.........s......................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................... 222211111119091037325131256288808 ADMINISTRATION OF POSF BY INHALATION TO RATS...................................................... 298 MSCICARNONAINNGAELLYESCIST.R...O...N....M....I.C...R...O...S..C...O...P..E....E...X...A...M...I..N...A...T...I.O...N....A...N...D....X...-..R...A...Y................................... 369 ANALYTICAL PHASE REPORT...................................................................................................... 518 HEYUENTRIENSGEDAORNCHRECSEENATRRCEHGCLPENCTORMEPGLLIAPNCCOEMSPTLAIATNECMEESNTTAS.T..E...M....E..N....T..S..................................................... 773385 Volume 1................................................................................................................................................ 1 Volume 2 ................................................................................................................................................ 366 : 368 : MIN 313/023622 SCANNING ELECTRON MICROSCOPE EXAMINATION AND X-RAY MICROANALYSIS Plymouth Electron Microscope Unit Scanning Electron Microscope Examination and X-Ray Microanalysis. Study Number: MIN313R Huntingdon Life Sciences Huntingdon Cambs PE28 4HS Plymouth Electron Microscope Unit University of Plymouth Drake Circus Plymouth PL 48AA 01752 233092 : 369 : MIN 313/023622 Materials and Methods 1. SEMexamination of urinary bladdertissue samples: eStuhbasnaoml)palensd(carpitpicraolxipmoaintteldyri0e.d5(pxro0t.5occmol)atwtaecrheedc)u.tDfrryomsamfixpeledstwisesrueemsaomunptleeds o(nsuspppelcieimdeinn s7tu0%bs with colloidal silver adhesive, sputter coated with gold and examined in a JEOL 5600 SEMat 15kV. Dry samples as supplied were carbon coated and examined in a JEOL 6100 SEM at 15kV. X-ray data were collected and analysed with an Oxford Instruments ISIS X-Ray Analysis system. : 370 MIN 313/023622 Specimen Preparation for Scanning Electron Microscopy Critical Point Drying (CPD) 1. Fix freshly excised sample appropriately (eg. 2.5% Glutaraldehyde in 0.1M phosphate buffer) 2. Wash inbuffer - 3x 15 minutes 3. Dehy35d00r%%ate--i11n55etmmhiiannnuuottleessseries 70% -15 minutes 9100%0%-1-155mmininuutetses 100% -15 minutes 4. Fill CPD chamber with 100%ethanol and cool to 10C or less 5. Place specimens in CPD chamber 6. Close and flood with liquid carbon dioxide 7. Exhaust alcohol from chamber. 8. Leave sample 30 minutes in chamberto infiltrate with carbon dioxide. 9. Exhaust remaining ethanol 10. Heat chamber to critical point 11. Vent carbon dioxide gas fromchamber 12. Remove sample from chamber and mount for SEMexamination. : 371 : MIN 313/023622 Results 1. SEMExamination ofUrinary Bladder Epithelium. rtSoeampmrapoinldeeudc1e9aan-ddoeniqmluyaatgteweiomquiamagleaitsgyeo,sfutwnhdeeerrseattmhaekpeloenp..eTrahteinegpcitohnedliiutimonhsaudsesdepfaorratthede fsrtuomdy,thweersaeminpalpe,prnooprciealtles : 372 : MIN 313/023622 : 373 : MIN 313/023622 : 374 : MIN 313/023622 : 375 : MIN 313/023622 : 376 : MIN 313/023622 : 377 : MIN 313/023622 : 378 : MIN 313/023622 : 379 : MIN 313/023622 : 380 : MIN 313/023622 381 MIN 313/023622 : 382 : MIN 313/023622 383 MIN 313/023622 : 384 : MIN 313/023622 385 MIN 313/023622 : 386 : MIN 313/023622 : 387 : MIN 313/023622 : 388 : MIN 313/023622 : 389 : MIN 313/023622 : 390 : MIN 313/023622 391 MIN 313/023622 : 392 : MIN 313/023622 : 393 : MIN 313/023622 : 394 : MIN 313/023622 : 395 : MIN 313/023622 : 396 : MIN 313/023622 : 397 : MIN 313/023622 : 398 : MIN 313/023622 : 399 : MIN 313/023622 : 400 : MIN 313/023622 : 401 : MIN 313/023622 2. SEM/X-Ray analysis of Urine samples Rstreupcrteusreentaantdivedeipmoasigtems oarrpehporloogvyid.ed from the supplied dried samples to illustrate typical crystal Xel-eRmaeyntaanl acloymsipsosspiteicotnr,aafnrdomcomthpeossuitpiopnlieodf sdpreiecdifiscacmrypslteasls(laanbdeldleedpoMsitIsN(a3s1l3aRbe),lletdo)sahroewprgoevnideerdal. : 402 : MIN 313/023622 : 403 : MIN 313/023622 : 404 : MIN 313/023622 : 405 : MIN 313/023622 : 406 : MIN 313/023622 : 407 : MIN 313/023622 : 408 : rVO'MIpWieIwrutat.oInrIAU:InP1AClymouth EM Unit Job : MIN 313 Recovery cps control r (21/05/02 12:19) MIN 313/023622 : 409 : Operator : Plymouth EM Unit Pliani * n A n Job : MIN 313 Recovery cps 1r (21/05/02 12:20) MIN 313/023622 Energy (keV) : 410 : Operator : Plymouth EM Unit Job : MIN 313 Recovery 4r (21/05/02 13:19) MIN 313/023622 Energy (keV) : 411 : Operator : Plymouth EM Unit r'IiAm nA Job : MIN 313 Recovery cps 5r (21/05/02 09:23) MIN 313/023622 Energy (keV) : 412 : Plianl OperatoKrA:MPAlymouth EM Unit viivi u . i iui ic Job : MIN 313 Recovery cps 6r (21/05/02 09:27) MIN 313/023622 Energy (keV) : 413 : rii* .Operator : Plymouth EM Unit Job : MIN 313 Recovery 7r (16/05/02 08:43) MIN 313/023622 Energy (keV) : 414 : Operator : Plymouth EM Unit Job : MIN 313 Recovery cps 8r (16/05/02 08:51) MIN 313/023622 Energy (keV) : 415 : Operator : Plymouth EM Unit PliAnf * Job : MIN 313 Recovery cps 9r (16/05/02 08:57) MIN 313/023622 Energy (keV) : 416 : n;i4 Operator : Plymouth EM Unit Job : MIN 313 Recovery cps 10r (16/05/02 09:02) MIN 313/023622 Energy (keV) : 417 : Operator : Plymouth EM Unit r. ianf n n n o Job : MIN 313 Recovery cps 11r (21/05/02 13:23) MIN 313/023622 Energy (keV) : 418 : Operator : Plymouth EM Unit *An Job : MIN 313 Recovery cps 13r (21/05/02 09:31) MIN 313/023622 Energy (keV) : 419 : Operator : Plymouth EM Unit nAn Job : MIN 313 Recovery cps 15r (21/05/02 09:35) MIN 313/023622 Mg s H Na Energy (keV) : 420 : Operator : Plymouth EM Unit Pliant n A n a Job : MIN 313 Recovery cps 16r (21/05/02 09:39) MIN 313/023622 Energy (keV) : 421 : Plianf *Operator : Plymouth EM Unit Job : MIN 313 Recovery cps 20r (16/05/02 09:08) MIN 313/023622 Energy (keV) : 422 : Operator : Plymouth EM Unit PiiAni nrma Job : MIN 313 Recovery cps 21 r (21/05/02 09:44) MIN 313/023622 ____ Energy (keV) : 423 : riiOperator : Plymouth EM Unit lent Job : MIN 313 Recovery cps 22r (21/05/02 09:50) MIN 313/023622 Energy (keV) : 424 : MIN 313/023622 : 425 : ri;Operator: Plymouth EM Unit Ant nnn Job : MIN 313 Recovery 26r (16/05/02 09:17) MIN 313/023622 Energy (keV) : 426 : Operator : Plymouth EM Unit filiant n n n a Job : MIN 313 Recovery 27r (16/05/02 09:23) MIN 313/023622 Energy (keV) 427 : Operator : Plymouth EM Unit i'll M A M A Job : MIN 313 Recovery cps 28r (16/05/02 10:35) MIN 313/023622 20 Energy (keV) : 428 : PliantOperator : Plymouth EM Unit Job : MIN 313 Recovery 30r (16/05/02 10:40) MIN 313/023622 Energy (keV) : 429 : Operator : Plymouth EM Unit riia n t * n n n A Job : MIN 313 Recovery cps 33r (21/05/02 10:00) MIN 313/023622 Energy (keV) : 430 : O perator: Plymouth EM Unit nlient n n n o Job : MIN 313 Recovery cps 34r (21/05/02 10:04) MIN 313/023622 Energy (keV) : 431 : Operator : Plymouth EM Unit f'Honf nnno Job : MIN 313 Recovery cps 35r (21/05/02 10:09) MIN 313/023622 Energy (keV) : 432 Operator : Plymouth EM Unit lilbnt * n n n Job : MIN 313 Recovery 36r (21/05/02 10:13) MIN 313/023622 Energy (keV) : 433 : Operator : Plymouth EM Unit nliont - n n n o Job : MIN 313 Recovery cps 38r (16/05/02 10:44) MIN 313/023622 Energy (keV) : 434 : Oi Ipieanr4at*ortrA:r Plymouth tA EM Unit Job : MIN 313 Recovery cps 39r (16/05/02 10:47) MIN 313/023622 Energy (keV) : 435 : Operator : Plymouth EM Unit n io n t rrtna Job : MIN 313 Recovery CDS 40r (16/05/02 10:55) MIN 313/023622 Energy (keV) : 436 O perator: Plymouth EM Unit fillA ni * n A n a Job : MIN 313 Recovery cps 42 background (15/05/02 09:53) MIN 313/023622 Energy (keV) : 437 : Operator : Plymouth EM Unit r . lA n f rtrtn o Job : MIN 313 Recovery 42 large crystal (15/05/02 09:56) MIN 313/023622 Energy (keV) : 438 : Operator : Plymouth EM Unit P.lionf *n A n o Job : MIN 313 Recovery 43R crystal (15/05/02 10:10) MIN 313/023622 Energy (keV) : 439 : MIN 313/023622 : 440 : Operator : Plymouth EM Unit nlitrt n A n a Job : MIN 313 Recovery 45r (15/05/02 10:21) MIN 313/023622 20 Energy (keV) : 441 : MIN 313/023622 Operator: Plymouth EM Unit Client! none Job : MIN 313 Recovery 50r (15/05/02 10:56) MIN 313/023622 443 : MIN 313/023622 : 444 : MIN 313/023622 : 445 : O perator: Plymouth EM Unit Client: none Job : MIN 313 Recovery 53r (15/05/02 11:11) MIN 313/023622 : 446 : rO.ipieenriat' onrn:nPalymouth EM Unit Job : MIN 313 Recovery 55r (15/05/02 11:17) MIN 313/023622 Energy (keV) : 447 : Or.lpioenrtatonrn:nPalymouth EM Unit Job : MIN 313 Recovery 58r (15/05/02 12:20) MIN 313/023622 Energy (keV) : 448 : rOJ piaenrtatonrn:nPlymouth EM Unit Job : MIN 313 Recovery cps 59r (15/05/02 12:25) MIN 313/023622 Energy (keV) : 449 : Operator : Plymouth EM Unit niifinf nono Job : MIN 313 Recovery cps 60r (21/05/02 13:26) MIN 313/023622 Energy (keV) 450 : Operator : Plymouth EM Unit niiflnt nono Job : MIN 313 Recovery cps 61 r (21/05/02 13:30) 30--I MIN 313/023622 Energy (keV) : 451 : Operator : Plymouth EM Unit Client nnne Job : MIN 313 Recovery 67r (21/05/02 12:08) MIN 313/023622 Energy (keV) : 452 : nOiipftenrtatonrrt:nPolymouth EM Unit Job : MIN 313 Recovery cps 66r (21/05/02 12:14) MIN 313/023622 Energy (keV) : 453 : O perator: Plymouth EM Unit Client: none Job : MIN 313 Recovery 70r (21/05/02 12:05) MIN 313/023622 Energy (keV) : 454 : O perator: Plymouth EM Unit Client; none Job : MIN 313 Recovery 71 r (21/05/02 12:00) MIN 313/023622 Energy (keV) 455 : Operator Plymouth EM Unit Client none Job : MIN 313 Recovery 74r (21/05/02 11:56) MIN 313/023622 Energy (keV) : 456 : nOiipfetnrtatonrr*:nPlymouth EM Unit Job : MIN 313 Recovery cps 75r (21/05/02 11:52) MIN 313/023622 Energy (keV) : 457 : Plymouth Electron Microscope Unit MIN 313/023622 Scanning Electron Microscope Examination and X-Ray Microanalysis. Study Number: MIN313 For: HPHCEauum2nn8ttbiinns4ggHddSoonnLife Sciences PPDPULllrnyya4immkv8eeooAruuCsttAiihhtrycEuolsefcPtrlyomnoMuitchroscope Unit 01752 233092 : 458 : Materials and Methods MIN 313/023622 dDartya swaemreplceosllaesctseudpapnlidedanwaelryesecdarwbiothnacnoaOtexdfoarnddInesxtarummineendtsiInSIaSJXE-ORLay61A0n0alSyEsiMs syatste1m5k.V. X-ray Liquid samples as supplied were centrifuged, a 30pl droplet from each sample was placed on a carbon stub, air dried, carbon coated and examined as described for the supplied dry samples. : 459 : Results 1. SEMExamination of Urinary Bladder Epithelium. MIN 313/023622 : 460 : MIN 313/023622 : 461 : MIN 313/023622 : 462 : MIN 313/023622 : 463 : MIN 313/023622 : 464 : MIN 313/023622 : 465 : MIN 313/023622 : 466 : MIN 313/023622 : 467 : MIN 313/023622 : 468 : MIN 313/023622 : 469 : MIN 313/023622 : 470 : MIN 313/023622 2. SEM/X-Ray analysis of Urine samples Rstreupcrteusreentaantdivdeeipmoasigtems oarrpehporloogvyid.ed from the supplied dried samples to illustrate typical crystal X-Ray analysis spectra from the supplied dried samples (labelled MIN 313), to show general eSliemmileanrtlayl, cspomecptroasitfioornt,haensdupcopmliepdosliiqtiuoindosafmsppelceisfiacrecrpyrsotvaildseadnd(ladbeeplolesditsM(aIsNla3b13eall)e.d) are provided. : 471 : MIN 313/023622 : 472 : MIN 313/023622 : 473 : MIN 313/023622 : 474 : MIN 313/023622 Specimen Preparation for Scanning Electron Mifrnspnpy Critical Point Drying (CPD) 1. Fix freshly excised sample appropriately (eg. 2.5% Glutaraldehyde in 0.1Mphosphate buffer) 2. Wash in buffer - 3x 15 minutes 3. Dehydrate in ethanol series 30%- 15 minutes 975000%%%---111555 mmmiiinnnuuuttteeesss 100%-15 minutes 100% - 15 minutes 4. Fill CPD chamber with 100%ethanol and cool to 10Cor less 5. Place specimens in CPD chamber 6. Close and flood with liquid carbon dioxide 7. Exhaust alcohol fromchamber. 8. Leave sample 30 minutes in chamber to infiltrate with carbon dioxide. 9. Exhaust remaining ethanol 10. Heat chamber to critical point 11. Vent carbon dioxide gas fromchamber 12. Remove sample from chamber and mount for SEM examination. : 475 : O perator: Plymouth EM Unit C lie n t: andrew lawrence HLS Job: MIN/313 owni iruitwm il y w v iu u r w c i J MIN 313/023622 Energy (keV) : 476 : CDS O perato r: Plymouth EM Unit C lien t: andrew lawrence HLS Job: MIN/313 i iR 1 r p n t r o r i o n n c iti / 0 7 /wno.r/ nu oc -iiqu .uc uqi\ MIN 313/023622 Energy (keV) : 477 : O perator: Plymouth EM Unit C lien t: andrew lawrence HLS BJOo b : MIN/3/O1T3/HO/HO MIN 313/023622 Energy (keV) : 478 : O perato r: Plymouth EM Unit C lien t: andrew lawrence HLS J o b : MIN/313 R 9 h a r l i\ngir oV Wi IinIHV / 9 7 (/ nWoU / nV&o. 4IVQ.-Un\o/I\ MIN 313/023622 Energy (keV) : 479 : O perato r: Plymouth EM Unit C lien t: andrew lawrence HLS Job: MIN/313 cps JWtMIW I f JW. 1 ^ . I MIN 313/023622 20 Energy (keV) : 480 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence HLS JhAo brr:vM/ctIaN/3(0173ir\0 ir\0 cps MIN 313/023622 Energy (keV) : 481 : O perator: Plymouth EM Unit C lien t: andrew lawrence HLS J o brr:uMc tIaNl /3/0173/n o /n o 1 Q-1 P^ MIN 313/023622 Energy (keV) : 482 : O perator: Plymouth EM Unit C lie n t: andrew lawrence HLS Job: MIN/313 p n /e ta I /O T /n o /n o MIN 313/023622 Energy (keV) : 483 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence HLS J7o b : MIN/t3O1I3/nO/CIO 60 MIN 313/023622 Energy (keV) : 484 : O p e ra to r: Plymouth EM Unit C lie n t: andrew lawrence HLS Job: MIN/313,r4 /07/no/no -m.C7\ MIN 313/023622 Energy (keV) : 485 : O perator: Plymouth EM Unit C lien t: andrew lawrence HLS J o b : MIN/313 oo oo o iy s u a i \/O.iTi/\nj o.i/ n\j o. o.\nj ..n\j o*.\) 80 MIN 313/023622 20 Energy (kev) : 486 : O perator: Plymouth EM Unit C lien t: andrew lawrence HLS Jo b : MIN/313 MIN 313/023622 Energy (keV) : 487 : O perator: Plymouth EM Unit C lient: andrew lawrence HLS Job: MIN/313 HQ r'n/c+nlc /07/H0/00 MIN 313/023622 Energy (keV) : 488 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence HLS Jono v/w b/O:ITMI/InNo//3n1o3Co.n\J-. 4I\oJ\I MIN 313/023622 Energy (keV) : 489 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence HLS J o b : MIN/313 jQO rvni f evtiwa i /O Ti // Dw&Oi/vnco. co.nv .- - t| ouy\ 100 MIN 313/023622 Energy (keV) : 490 : O perato r: Plymouth EM Unit C lien t: andrew lawrence HLS J o b : MIN/313 Qx ^r\/e+Qi y/j0-17// C\0/wr\eO. 4on-oc\ MIN 313/023622 Energy (keV) : 491 : O perator: Plymouth EM Unit C lie n t: andrew lawrence HLS JCJo3bho: nMlcINnm/3i1in3rl |/Mwi\yivunu /07/n0/A0 / o.\nJ ,-Co.\oJf\ MIN 313/023622 Energy (keV) : 492 : O perator: Plymouth EM Unit C lient: andrew lawrence HLS Job: MIN/313 QA r^rv/cto / 0 7 /A 0 /n o o n - o o \ CDS MIN 313/023622 Energy (keV) : 493 : O perato r: Plymouth EM Unit C lien t: andrew lawrence HLS Job: MIN/313 QA r\ / 0 7 /HO /flO OA*OQ\ 100 50 MIN 313/023622 Energy (keV) : 494 : O perator: Plymouth EM Unit C lien t: andrew lawrence HLS J Ko b : MINI/3/O1T3/nO/nO 00-i!0\ 100 50 MIN 313/023622 Energy (keV) : 495 : O perator: Plymouth EM Unit C lien t: andrew lawrence HLS J o b : MIN/313 o r ract mR/n^/no ion-3\ cps MIN 313/023622 Energy (keV) : 496 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence HLS Job: MIN/313 0wt7l /oot /n c /n 'j/n o ywV(VV/V. -to nex 100 MIN 313/023622 Energy (keV) : 497 : O perato r: Plymouth EM Unit C lien t: andrew lawrence HLS Jqrob/':acMtIN/313 10<m\ 80 MIN 313/023622 20 Energy (keV) : 498 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence HLS Job: MIN/313 q q pact /ns/n o/n o -lo om 100 MIN 313/023622 Energy (keV) : 499 : O p e ra to r: Plymouth EM Unit C lie n t: andrew lawrence Job MIN 313 A H v A r'rv/ctal H I cps -r-r/ MIN 313/023622 Energy (keV) : 500 : O p e ra to r: Plymouth EM Unit C lient: andrew lawrence Job : MIN 313 A m /n-i/n-p cps MIN 313/023622 Energy (keV) : 501 : O p e ra to r: Plymouth EM Unit C lie n t: andrew lawrence Job: MIN 3 1 3 A ftftA M -i/n s/n o cps MIN 313/023622 r -- i----1----- 1-----j-J 20 Energy (keV) : 502 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence Job : MIN 313 A R7A /M /n'i/no 50\ MIN 313/023622 Energy (keV) : 503 : O perator: Plymouth EM Unit C lie n t: andrew lawrence Job : MIN 313 A hhA n-l/n'i/no cps MIN 313/023622 Energy (keV) : 504 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence Job MIN 313 A r q a n 1/nz/no i a -a i \ cps MIN 313/023622 Energy (keV) : 505 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence Job: MIN 3 1 3 A 90A (11/03/02 14:49' MIN 313/023622 Energy (keV) : 506 : O perator: Plymouth EM Unit C lien t: andrew lawrence Job : MIN 313 A 91 a n a /n s /n ? nc>aa\ MIN 313/023622 Energy (keV) : 507 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence 9J9oAb MMSIN/ns3/1n3o A 30 MIN 313/023622 Energy (keV) : 508 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence Job: MIN 3 1 3 A 93a (14/Q3/Q2 09:09' cps MIN 313/023622 Energy (keV) : 509 : O perator: Plymouth EM Unit C lien t: andrew lawrence 9Jo4ba :(1MAINM 3n1o3 0A0-1^ MIN 313/023622 Energy (keV) : 510 : Operator : Plymouth EM Unit Client andrew lawrence Job MIN 313 A 95a (14/Q3/Q2 09:15' MIN 313/023622 Energy (keV) : 511 : O perator: Plymouth EM Unit C lie n t: andrew lawrence Job M N 313 A QRa M A in u n o na-icn MIN 313/023622 20 Energy (keV) : 512 : O perator: Plymouth EM Unit C lient: andrew lawrence 7o no/no rwvo>i\Job: MIN 313 A sjfk/i a ^ i--r/w uw/xTy MIN 313/023622 Energy (keV) : 513 : Operator : Plymouth EM Unit Client andrew lawrence Job MIN 313 A oo /-i.d/ivi/no no o7\ MIN 313/023622 Energy (keV) : 514 : O p e ra to r: Plymouth EM Unit C lien t: andrew lawrence JQoQba:MMiiI/Nn^3/1n3o Ana-s-n cps MIN 313/023622 Energy (keV) : 515 : Operator : Plymouth EM Unit Client andrew lawrence Job MIN 313 A QQa rrvcta c (14/n3/n9 MIN 313/023622 Energy (keV) : 516 : O perato r: Plymouth EM Unit C lien t: andrew lawrence Job: MIN 313 A jinwnu-aa ^/I(-/TfnW'Wj//no no f MIN 313/023622 Energy (keV) : 517 : ANALYTICAL PHASE REPORT MIN 313/023622 ANALYTICAL PHASE REPORT STUDY TITLE APdermfliunoisrtoroacttioannetsouClfoDnyRlaFtslufoorrid1e3 (WPOeeSkFs;FTo-l7lo6w61e.d4)bTyoax4ic-WityeSektuRdyecboyveIrnyhaPlaertiioond DATA REQUIREMENTS Analytical Method Requirements STUDY DIRECTOR HuntingTtoenrrLyiJfe. KSecniennyces, Ltd. ANALYTICAL PHASE COMPLETED ON March 10, 2004 PERFORMING LABORATORY StP3ah0tEeo5nx8CyeoR:glee8lnes1ge4Rae-r,e2csP7heA2aD-r1c1r0h6iv38e901 STUDY SPONSOR 3SMt.BPCuaoiulrdlp,ioMnrgaNt2e25T05-o12x3Ei3c--o03l22o2g0y PROJECT ExPyrgoetnocSotluNdyumNbuemrb: eMr:IN02/331-0376 Total Pages: 217 : 518 : MIN 313/023622 Exygen Study No.: 023-076 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT EEAcPoPrxxdnieygmndrgycfuieeilnpuncnitloseeRtrdsroeSaosottfecuifooatdraGnrynco3hetoMo.sdNulCufLComDanobbryopeRlrroaarFttasol0ture2fyoo3rTrP-i0dor17aex3c6ict,(ioWcPleoOtegh(eSayekFs,s;rwaeFTnvaoais-lsl7leyop6dtw6iecr1ieanfd.lo4r1)bm9py9Teh7daoa)sx,ie4inEc-iNWtcoyVofem/eMSkptthluCiRead/eCnyccHosebtvEuyewdMryiytI(hn9Ph8eeOa)nr1ltEai7iottCidlobe,Dndy EPRrxiciynhgcaeirpndaRlAIe.nsevaerstcihgator HsttauurndtytyinJDg.TidrKoencentLonryife Sciences Ltd JS3oMphonnCsBoorurptReonreahptroeefTfseonxtiactoivloegy Exygen Research : 519 : Date DCt. Date Date Page 2 of 217 MIN 313/023622 Exygen Study No.: 023-076 QUALITYASSURANCE STATEMENT Ea7n6xa6yl1gy.et4inc)aRTl eospxehiacaristceyh'SostfuQdutyhaelbitysytIuAndhsysaularetaninotincteleAUdd,nmi"tiPnreiesrvtfrileauwtoioerdonoEtcotxayCngDeesnuRlSfaottunsdyfylorNF1ulu3moWrbiederee0k2(sP3FO-0oS7llF6o;,wteThdebaaSlcytlucodaarypdp4Diln-iiWcgraetceboteloekErxGaRynogedoecdnotovLRemraeyabsneoaraPargetcerohmiro'ysedn"SPt.t.raancAdtialclredrSOetvapineedrwaaetriddnsg.pPhraAoslcelesdfiuwnrdeerisne,gtshinewspSeetrucetdeyrdepPfororortteodccootnlo,dautnhcdet Phase InsDpaetceted DMtoataEenxaRaygnegedpemonretPneItd 1. Extraction, AInnsatrluymsisenbtyation 10/07,08/02 11/22/02 2. Raw Data Review 121/10/22,70,239/0,2 03/17/03 3. Raw Data Review 11/27,12/02-05/02 1122//1129//0022, 4. Raw Data Review 03/14,17/03 0077//1271//0033, 5. RDerapfotrAt Rnaelvyiteiwcal 10/29-31/03 1013//1110//0034, 6. RFienpaolrAt Rnaelvyiteiwcal 03/08/04 0033//0180//0044, SDtuaTdteyesRDt eFirpaeoccrittloeitrdyatnod Management 12/09/02 03/10/04 04/16/03 03/10/04 03/10/04 03/10/04 ft /KMQuiwalaityNAabsestuarnaince Auditor f a t r c L (of c>y Date Exygen Research Page 3 of 217 : 520 : MIN 313/023622 Exygen Study No.: 023-076 CERTIFICATION OFAUTHENTICITY Tthheisrarwepdoartta, ffoorrEthxeysgteundyS.tudy Number 023-076, is a true and complete representation of Submitted by E3S(80txa15yt48ge)eCR2ne7oRs2lel-eea1sgre0eca3,hr9PcDhAri1v6e801 Principal Investigator, Exygen: RPErxiceyhsgiadernednRtAe.s(eaarraczhzi /D - nM rL Date Exygen Research Facility Management: EVxicyegePnreRsiedseenatrch Study Director, Huntingdon Life Sciences, Ltd H:eurnfytiTnTgdKoennnLei;fe Sciences, Ltd Sponsor Representative, 3M: Date< * /'r DateY w u _ 2 C t X l ~ J3oMhnCBorupteonrahtoefTf oxicology Exygen Research Date Page 4 of 217 521 : MIN 313/023622 Exygen Study No.: 023-076 STUDY IDENTIFICATION APedrmfliunoisrtoroacttioannetsouClfoDnyRlaFtslufoorrid1e3 (WPOeeSkFs;FTo-l7lo6w61e.d4)bTy oax4ic-WityeSektuRdyecboyveIrnyhaPlaertiioond PROTOCOL NUMBER: MIN/313 EXYGEN STUDY NUMBER: 023-076 TYPE OF STUDY: Analytical SAMPLE MATRIX: Rat Liver, Serum, andUrine TEST SUBSTANCES: SPONSOR: PPPeeenrrfftllauudooerrcooaoofccluttaaonnreeossouuclltffaoonnnoayitlceFA(lPucFoidrOid(SPe)F(aOPnOAdS) F), B3SMtu.iPlCdaiounrlg,pMo2r2aN0te-52T5E1o-30x2i3c-o3l2o2g0y STUDY DIRECTOR: PTHWAHCEealuucrom2nnoro8ttynbliilnnbr4Jegig.uHydddKrgSRoyoeennosnhanLdiyrifee, Sciences England Ltd SPONSOR REPRESENTATIVE: JB3SoMtu.hiPnlCdaBiounrulg,ptMoe2nr2aNh0to-e52fTf5E1o-30x2i3c-o3l2o2g0y PERFORMING LABORATORY: E3S0txa5yt8geeRCneoRsleleeasgreeca,hrPcDhAri1v6e801 TAINMAELTYATBILCEA:L PHASE EEAStxxnuppadeelyyrriitImmincaeeitnnliattPaathilloaTSnsteeaDrrCmattoDienm:aatpteil:oentioDnatDea:te: 00119320////21020069////00001224 Exygen Research Page 5 of 217 : 522 : MIN 313/023622 Exygen Study No.: 023-076 PRO TECT PERSONNEL TThhee SfotulldoywDinigrepcteorrsofnonretlhifsropmroEjexcytgweansRTeesrerayrJc.hKweenrneyaastsoHcuiantteindgwdoitnhLviafreioSucsiepnhcaesseLstodf. the study: Name Richard A. Grazzini Emily Decker Paul Connolly Karen Risha Lawrence Ord Rickey Kelley Chas Simons Carisa Kelley Joe Gallagher Chris Pfleegor Xiaoming Zhu Title President Scientist Technical Lead-LC/MS Scientist Sample Custodian Sample Custodian Technical Lead-GC/MS Technician Scientist Scientist Technician Exygen Research : 523 : Page 6 of 217 MIN 313/023622 Exygen Study No.: 023-076 TABLE OF CONTENTS TGQCIEOUTRAOLTLEDIIFPLTIAYACGBAAEOTS.IR.S.O.UA.N..RT..OOA...FRN...YAC...UE.P.T.RS..H.AT..EAC..N.TT..TIE..C.IM.CE...EI.CT.N.O.Y.T..M..........P......L.........I...A.........N......C.........E..........S........T......A.........T.........E.......M...........E.........N.........T...................... PSn mR1TOUT iJU-kETICr tUTtJnCPt 'IEiNtRi1i 'S1l lOT 1NLNAa rE1r1Lr U/ ^.1.\.N.T.........................................................,......................;........................................................................................... TABLE OF CONTENTS.......................................................................... LIST OF TABLES..................................................................................... LIST OF FIGURES................................................................................... LIST OF APPENDICES........................................................................... 1.0 SUMMARY....................................................................................... 2.0 OBJECTIVE....................................................................................... 3.0 INTRODUCTION.............................................................................. 4.0 TEST SYSTEM.................................................................................. 5.0 REFERENCE MATERIAL................................................................ 6.0 DESCRIPTION OF ANALYTICAL METHOD............................... 6.1.1 PFOS and PFOA Extraction Procedure........................................ 6.1.2 POSF Extraction Procedure.......................................................... 6.2 Preparation of Standards andFortification Solutions.................... 6.3 Chromatography............................................................................... 66..54.1InDstersucmriepnttioSnenosfiLtiCvi/tMy.S../.M....S...I.n..s..t.r.u..m...e..n..t..a..n..d...O..p..e..r..a..t.i.n..g...C..o..n..d..i.t..i.o.n...s. 6.5.2 Description of GC/MS Instrument and Operating Conditions...... 6.6.1 PFOA and PFOS Quantitation andExample Calculation............. 6.6.2 POSF Quantitation andExample Calculation............................... 7.0 EXPERIMENTALDESIGN.............................................................. 8.0 RESULTS........................................................................................... 91.00.0CROENTCELNUTSIOIONNOSF...D...A...T...A...A...N...D....S..A...M....P..L...E..S............................................................................ ....3142 ,,.56 ...1...7890 1111 12 12 1132 111344 1155 15 16 211708 .222110 Exygen Research : 524 : Page 7 of 217 MIN 313/023622 Exygen Study No.: 023-076 LIST OF TABLES Table I. Summary of PFOS in Control Rat Liver Samples ........................................23 Table H Summary of PFOS in Control Rat Serum Samples .......................................23 Table ILL Summary of PFOS in Control Rat Urine Samples.........................................23 Table IV. Summary of PFOA in Control Rat Liver Samples....................................... 24 Table V. Summary of PFOA in Control Rat Serum Samples.......................................24 Table VI. Summary of PFOA in Control Rat Urine Samples........................................24 Table VII. Summary of POSF in Rat Liver Control Samples.........................................25 Table VU. Summary of POSF in Rat Serum Control Samples.......................................25 Table IX. Summary of POSF in Rat Urine Control Samples.........................................25 Table X. Summary of PFOS Fortification Recoveries in Rat Liver.............................26 Table XI. Summary of PFOS Fortification Recoveries in Rat Serum............................27 Table XII. Summary of PFOS Fortification Recoveries in Rat Urine.............................28 Table XIII. Summary of PFOA Fortification Recoveries in Rat Liver.............................29 Table XTV. Summary of PFOA Fortification Recoveries in Rat Serum...........................30 Table XV. Summary of PFOA Fortification Recoveries in Rat Urine............................31 Table XVI. Summary of POSF Fortification Recoveries in Rat Liver.............................32 Table XVEL Summary of POSF Fortification Recoveries in Rat Serum..........................33 Table XVIII. Summary of POSF Fortification Recoveries in Rat Urine..........................34 Table XIX. Summary of PFOS Residues in Rat Liver Samples.......................................35 Table XX. Summary of PFOA Residues in Rat Liver Samples.......................................40 Table XXI. Summary of POSF Residues in Rat Liver Samples.......................................45 Table XXII. Summary of PFOS Residues in Rat Serum Samples..................................50 Table XXIII. Summary of PFOA Residues in Rat Serum Samples............................. 55 Table XXIV. Summary of POSF Residues in Rat Serum Samples..................................60 Table XXV. Summary of PFOS Residues in Rat Urine Samples...................................65 Table XXVI. Summary of PFOA Residues in Rat Urine Samples..................................69 Table XXVH. Summary of POSF Residues in Rat Urine Samples..................................73 Exygen Research Page 8 of 217 : 525 : MIN 313/023622 Exygen Study No.: 023-076 LIST OF FIGURES Figure 1. Typical Calibration Curve for PFOS................. Page 78 Figure 2. Typical Calibration Curve for PFOA..............................................................79 Fionre 3 -- o ------ T~vjnrical Calibration ------------- Curve for POSF............................................................... 80 Figure 4. ChromatogramRepresenting a 0,1 ng/mL standardfor PFOSandPFOA....... 81 Figure 5. ChromatogramRepresenting a 25 pg/mL standard for POSF........................ 82 Figure 6. CPhFrOomAa(tEogxryagmenRIeDpr0e2s0en1t6i8n4g CaoCnotnrotrloAl ,RSaettL: i1v0er08S0a2mBp)l.e...f.o..r...P..F..O...S.....a.n..d.......83 Figure 7. C(EhxryogmeantoIDgr:a0m20R2e8p7r7e,seSnetti:n1g0a2C50o2nAtr)o.l..R...a..t.L...i.v..e.r...S..a..m...p..l.e...f.o..r..P...O...S..F..............84 Figure 8. PCFhOroAm,a(tEogxryagmenRIeDp:r0es2e0n1t6in8g2aCConotnrtorloAl R, aStetS:e0ru9m25S0a2mAp).l.e..f..o.r...P..F..O...S....a.n..d.....85 Figure 9. C(EhxryogmeantoIDgr:a0m20R1e6p8r2esCentrtli,nSgeat:C0o9n2t6r0ol2RBa).t..S..e..r.u..m....S..a..m...p...l.e..f..o.r...P..O...S..F..,..........86 Figure 10. CPFhOroAm,a(tEogxryagmenRIeDp:r0es2e0n1t6in8g3aCConontrtorlolAR, aStetU:r1in0e03S0am2Ap)le...f.o..r..P...F..O...S...a..n..d......87 Figure 11. C(EhxryogmeantoIDgr:a0m20R2e8p7r5esCentrtli,nSgeat:C1o0n1tr1o0l2RAa)t..U..r..i.n..e...S..a..m...p..l.e...f.o..r...P..O...S..F..,........... 88 TJT7^lgUIG l1OZ,. VPF^IOllVSJialinaidUPgiFaiOil A (ExyagimeninIgD:^U0I2I0U1U6I8rD4vouSft pIT^kIixYArWa,f Siveut:ui1iw0u08IvT0Mt+i2uVB*i a1).Cv.\..n1.i.1.t^/.f.5.t......... 89 Figure 13. PCOhrSoFm(aEtoxgyrgaemn IRDe:p0re2s0e2n8t7in7gSCpoknAtroSleRt:at1L02iv5e0r2fAor)t..i.f.i.e..d...a.t..5...p..g../.g...w...i.t.h.........90 Figure 14. oCfhProFmOaStoagnrdamPFROeApr(eEsexnytgineng CIDo:n0tr2o0l1R6a8t2SSeprukmAf,oSretti:fie0d10w0i2th021A0)n..g../.m...L.....91 Figure 15. CofhProOmSaFto(gErxaymgeRneIpDr:es0e2n0ti1n6g8C2oSnptkroAl R, SaettS:e0r9u2m60fo2rBti)f.i.e.d....w..i.t..h...5...p..g../.m...L.......92 Figure 16. CofhProFmOaStoagnrdamPFROeApr(eEsexnytgineng CIDo:n0tr2o0l1R6a8t3USrpinkeAfo,rSteifti:ed10w0i3th021A0)n..g../.m...L.......93 Figure 17. CPOhrSoFm(aEtoxgyrgaemn IRDe:p0re2s0e2n8t7in5gSCpoknAtr,olSeRta:t1U0r1i1n0e2fAor)t.i.f.i..e.d...a..t..5...p..g../.m....L...w...i.t.h.... 94 Figure 18. C(EhxryogmeantoIDgr:a0m20R3e5p5r3e,seSnptoinngsoRraItDL:i9v1erSSeat:m1p0le21fo0r2PAF)O...S....a.n..d...P...F..O...A............95 Exygen Research Page 9 of 217 : 526 : MIN 313/023622 : 527 : MIN 313/023622 Exygen Study No.: 023-076 1.0 SUMMARY Exygen Resarch extracted and analyzed rat liver, serum, and urine samples for the determination of perfluorooctanesulfonate (PFOS) and peritadecafluorooctanoic acid tl(di7PAe,,FtaieVOkrimA-ui)zn.aj-atruic\onc/no11r/aod\ fi/(n/paigpe_r_pft_clo_uu_ouEriisAoxoycrgt^ea\nnesMulefothnoydl flEuxorMid-e02(3P-O07S1F) (aAccpoprednindgixtoBE)xyagnedn Mforethtohde THvs1sswus1eaaeahsphorrmmlee/uiwuimddcppmmlehaiTwllmvete.iiwehanofisraniotancic,ldrzrsoihqetefrhud,suaiaqtneresootuiutectnneLdsdraerlefienOy.meotrathsurQ0isiteTmen.as1dpeLhtfeidoeraetmOorruhnnufQlLmedoiPsfmrLioFwufnmaroiOOrgtanreiPQsnAddo0eFe.uaf.1fOuacsoaqrnehSrmtiTuddnPmahaLeEfnOnPeoaxtadsFrtiSLaynrtOPFasmigdOxetFSeiirpQonnb1Oulni.yenm0Asfeo(afa,Eregorilfnu0airxaqesmc.yrc2auPahagtcmoOob-tehtmrynlpSia1aomvlFane.tef0Sradfriwiat1tnmxuriwc0neidtLxriwaooigasserrawthfososol1mt:laeri0fssvdfeu2so0ened.r.crr2tgieea3n/Tltrwsgi-eemveh0,araseem7sianrno4Ln.di2enndOd.l1e5Day0Qd0un.uj01dsniife.ignog0ng/r/5tg0gamof2PomaamL3Olrni-Lme1i0dSlnti7Fvhiwmt25reoea.iar)L5ddnst., PtddPdshaFeeeFemtttOOeeerpcccSaAtttlteeeeidddsilnni.viltlnetehePhrvveFaeeesnrOlalrayssmaSttottlpoiiofunvlrtee1h1itsrn2he5re,se81raa,sa0rn0mata0g0mtlpe0inudvlpegrenlsfi/ergnrmsro/esamLmarnsam.Lagnnme.pgTodlepenhdPfsl-ere.dFrfosreeOmPorteFwAamcnnOatogiensSnnedodn-indtlnoeh-fedrvettPoeheemOctrelestaSerctntadtFoeotsedlnsd8ere-ev2uldrete7mueevl0mtcseetlsncetsasotdgamet/5mdogipn3.pl1l5eela8T,ves0n,she60yrle0r0sara0onetnnfgonggwetge4/hdga/d7em.sf1frrLrn0Paooo.FtmnmOPsgTe/OnnAhrmooueSLnnirmFne. was no POSF detected in any of the rat urine samples. The average percent recoveries standard deviations for PFOS in rat liver, serum, and uavrienreagseampeprlceesntwreerceov9e6r%ies s1t1a%nd,ar1d02d%eviati1o4n%s f,oarnPdFO87A%inra1t1l%ive, rr,essepreucmtiv, ealnyd. uTrihnee samples were 99% 9%, 105% 14%, and 110% 17%, respectively. The average pweerrceen9t9%recov1e8r%ie,s92%stand1a8r%d,daenvdia9ti9o%nsfo1r8P%O, SreFspinecrtaivtelliyv.er, serum, and urine samples 2.0 OBJECTIVE T(sPphOeecSiomFb)je,enpcsteiorvffeluroaoftrltoihovicestrpaanhneadssueslewforaunsmatteosa(dPmeFtpeOlremSs)ia,ncaecnoldervdpeienlnsgtoatfodpePcerarofftlluuocooorroloooMccttEaaNnn/oe3si1cu3laf(coAindyp(lpPfelFunOodrAiixd)eAin). Exygen Research Page 11 of 217 : 528 : MIN 313/023622 Exygen Study No.: 023-076 3.0 INTRODUCTION TrtmrFahaenhlteesudiutlsoDhilPrvtroeiseeeddtrnpefeortoeaamr(rnnPdttdtieOihndtcselaeSaeettFrdfdailou,)eiulnmtsoi"enrMortsohmRfaoeePmaitcnhtretpaaeroUtslfndeiluroousilnion,otcsfeuro,oAosAfhiSfncnPeeitgxradOhualteyShmn(sPaFeei,nFssaiauaOnnfnllofyaAdrorslay)niLtsttaiihilnvfctieoevaeRrelrD(rmPtabehtFayteeenLHtGrhddimSvoeCs)etdie,e/nrMrPre,aumnetSSmirtioe.ifn"trnlslauueatomdomior,fonp"aPolMnoecedstrfea,ftPUlnuhuFersoosOiidrnnuoSeglofo"oftachntAanaeandnntdaeaPenslaF(yauPlOslslyFifosAotOintfchoSiaynre)ll TnthuhemeabsnetaurldyMyticIwaNla/es3x1ip3ne.irtiiamTtheedentoaannl atDelyretmicceianmlabteixeoprne6dr,aimt2ee0wn0t1aa,sl wOsthcaterontbdetahrtee29sw,tua2ds0y0S2de.pirteecmtobrersig2n0,ed20p0r2o,toacnodl 4.0 TEST SYSTEM Trehceeicvoendtrforlorzaetnlivoenr adnryd siecreumonusJeudnefor1t2h,e2m0a0t2rixanbdlanAkusgaunsdt m7,at2ri0x0f2orftrifoimcatiPoenls-Fwreeerze Biologicals, Rogers, Arkansas. Nr2e0icn0ee2itvyae-ndedigflrhootgzgerenadtoilnnivebdryr,yEnixcinyeegtaeytn-EepixgeyrhsgtoenrnantferlsoeamrnudmHp,ulanactniedndgsidneovnfernoLtzyief-nenisSntcoeirearnagctee.usroinneSseapmtepmlebserwe1r0e, Sample log-in and chain of custody information can be found in the raw data package copy of the storage records can be found in the raw data package associated with thisUOOUVIUIWU um/ iitllil tUVliliOc oLtUnUrUKj/r. UC ltUn riUa o^AV rf*r*r\rr\O w*i l l V>-l>Aw *IwfP^n/>t. %fi~tv p Y V O 'P* n'* R P C P ilf r h a tlH --fl t*--lT--If--t study. 5.0 REFERENCE MATERIAL TMAaannhladdaeyrlysiatct1onih5cra,aeall2dynt0sdait0camsa0ntlbodfirraseetornaddmtn.rdPe3afOMrrdiSgFEePrnaFwvtOaeirdsAo.nremTwchaeeensivtaearndleacTlaeyetitvciEehcdaxnlyoagslttoeagnEnydxoaaynrngddJenuPSnFeoeOrnv6Si,Jcwue2s0lay0sa2nr3ed,fcr2seot0imov0re2edSdifagrftmroEomazx-eyAnSg..liedgnrmTiochanheThe available information for the reference material is listed below. : 529 : MIN 313/023622 Exygen Study No.: 023-076 The molecular structures of test substances are given below: NamCMheo:elmePcFiucOlaalSrNWameige:ht:Pe4r9fl9u,oarososchtoawnensulfonate - NamMCheo:elemPcFiucOlaalrANWameige:ht:Pe4r1fl3u,oarsooschtoawnnoic acid NamCMheo:elmePcOiuclaSalFrNWameige:ht:Pe5r0fl2u,oarsooschtoawnnesulfonyl fluoride 6.0 DESCRIPTION OFANALYTICAL METHOD Tmdarihfeefeteihnraoecndnlaustldyswteaidecmrawepl ilmtveheesrtitszhhieoiossdnrsaeednEpdoxartMftot.e-mr02ath3ke-e0ma7n1ianaloynrsditsyEpoxofMgtrh-a0ep2hs3iac-m0al7pc1loAersrwewceetrrieoenucss.oemdTphfoleertrteehdviisstoesdtuamdllype.wthTofhdoesr 6.1.1 PFOS and PFOA Extraction Procedure Aaliq1u00otpoLf aulriqinueo,taonfdth0e.1segruomf tshaemlpivleer(1(.10.0mgLffoorr llaabboorraattoorryy ccoonnttrroollss)), w20e0repuLsetod 1fo.0rmthLe Exygen Research Page 13 of 217 : 530 : MIN 313/023622 Exygen Study No.: 023-076 extraction procedure. After fortification of appropriate samples, the serum and urine usmatahapdliimedqnteuupsoduotleept1ase0aonrwndfnmdeaotrLthnteaheenbwetsmrailowtimihvulalegpisTrlhlieyttdssepauerewcmpaweIptnroaltWeese2sdsa0thwrtoeaamenrnkr.LtseeofnewThrafrhiootecmerhdo~osTnfegdry2reoipu0tnmeimiomzIneeiaWeadnndcudahwtSteieusPstrarh.EimanTanecphdotliseelstauhssmamueanepmnldmil.vpe5ieslzeTremwshrsLewaefrnmoeeorrptfevhl~eoaecscre1estnweatmtoxemrneriifnpdeiutulrbgeftisoreeleodr.wuwa~geAnahrnd1est KJJ .JC i u i t u W tUi lUl ! OZ, 1*vU,TL / Ur t1f lwl lttr/tUtUina Mi l Urtli . J L ^ a ^ ll oo na irlvi mp i lwa nw/O Oo q h q 1 \/'7 p H K \ r T f 1/A / T Q / \ /f Q pw 1x wp w^ twr n c.TM r u \ / . 6.1.2 POSF Extraction Procedure Aetoxt56r00a-c1Cti0o-08n0ppLrCoacfleoidqruu~roet3.-o4Af mtfhteienrsufetorerustmiafincadanttdihouennrionafenaaaplnypdzreo0dp.1rbiaygteGofsCat/hmMepSllie.vse,rthweerseamuspeldesfowretrheeheated 6.2 Preparation of Standards and Fortification Solutions 0FAsdmo2riLslo3susmt-otoo0ilfoc7vtkneh1inai.osscgthfTas1noPhs0dltFeuoaOmtscritkdoSogncasw,konoaaldfsustebt1apiar.no0cridnnehappgrogiasdnft/ramgesPndotLFdhlouaOefnrtoAidvorAotn(liwucusfigoamcwursareesteptriuocre2tpnee,ppdtrs2aoter0afpe1o0nad0r2dr0aeopardnmusdarLsJitsptuoyawellyucciatitonfh8iniod,emcnd2ese0nawitn0tlhatr2aasEcntaoxpioonnyrlnde.tgepeonaanftr)sem1td0oien0cbtkhympogstedta/tamkhEniaLdxnnaMgobrldy1-. Afor0t.i1ficpagt/imonLstfaonrdtiafircdatainodnbsrtainngdianrgdtwheasvporluepmaereudpbtyot1a0k0inmgL10wmithLmofetthhean1o.l0. pg/mL mixed AandsevtaorifosutsancadlairbdrsatcioonntsaoinluintigonPsFiOn AtheanfodllPoFwOinSgwmaasnnperre:pared dilution of the 0.1 pg/mL 1InoiftiPaFl COoA000n00..0.000e...a111000.n152(dpPgF/mOLS)1 Volum111521e000 (mL) Diluted111111000000t000000o (mL) Final Cone. (pg/mL) 000000.....0.00000000000000152152 FAm215r9eos9tmtm0hooLcptdkhogEisf/stmxtashMnLoedlu-asb0ttryoi2doc3ndks-o,0isal7ausn1otd1Ailov0b.ni0rn0ioTgnfpgh-gPien/Omgs0tS.toL2hFcekcgwavslaooitbsalfurnptamdrhtaeeieorpdnuastrpsaseotntdalodunoat5dnri0aodJrnmdu(cwnLsoeoarwls1ruie1pttc,hirot2eenmp0da0ewrft2oheadrsaasnpapostrulpe.arpeitaccyori)fenidecindebniymtnrteaEattkhxioiaynnnggeoonl~f. Exygen Research Page 14 of 217 : 531 : MIN 313/023622 Exygen Study No.: 023-076 A set of standards containing POSF was prepared by dilution of the 1000 pg/mL: Initial Cone. (pg/mL)1 111000000000 1of POSF111000000000 Volu0m200.51...2e5515(mL) Diluted to (mL) 10 1100 111000 Final Cone. (pg/mL) 251500000 521500 Tpstrhoeerpeasdrtoaitcnikonsatcaarnnedfbariregdeforsauotnloudrtiion(n4thaendra2awllCdfa)otrawtiahfsiecsnaotciinoanotetdaninwditcuhasletih.birsartDieoopncourstmt.aenndtaartdiosnoluotfiosntasnwdaerrde 6.3 Chromatography Qraenutyeanontftiiotfnhiceatictmioonentroooffl PPsaFFmOOpAAlewsanacdsor~PreF8sOp.6oSnawdnidansg~at8oc.c8tohmme painlnisafhloyertdePrbFeyOteLSn.Ctio/PMneaStik/mMsewSs.eerleecntrootsdpertaeyc.teTdhine Q~anu3aal.yn5tteimfircienat.teinotnPioeonafktPismOweSeoFrfewPnOaosStaFdc.ectoemctpeldishinedthbey cGonCt/rMolS.livTerhesarmetepnletiocnortrimesepoonfdPinOgStFo wthaes 6.4 Instrument Sensitivity Tcohnecenstmraatliloenstofst0a.n00d0ar1dpga/mmoLuonft PFinOjeActeadnd PduFrOinSgantdhe25cphgr/ommLatfoogrrPapOhSicF. run had a : 532 : MIN 313/023622 Exygen Study No.: 023-076 HHPP ACuoltuomsanmOplveern HPLC Column:Genesis C8(Jones Chromatography), 2.1 mm x 50 mm, 4p Column Temp.: 35 C ' IMnjoebcitlieonPhVaosle.:(A15):pL2 mM Ammonium Acetate in W_ater FivlioOwDiiReartnea: se (jd0).3: mivLic/miiiiann.ui . T2112959i0440m....0500...500e %90A 9911000000 90 %1199111100000000B00 Ions monitored: APPnFFaOOlvASte nnMeeggoaadttiievvee Trans44i1t9i3o9n-->M>3o96n99itored ReteAntpiponr88oT..x68iimmaet(emin) O.S.Zinscription o Instrument: instrument ana viperaimg ^uiiuuiuns HChewrolemtta-tPoagcrkaaprhd/mmooddeell56987930mSaesrsiesselGecatsive detector Column: Restek RTX-502.2,60 m x 0.25 mm ID, 1.4 pm df Oven Temperature: Hfoorl0dmatin4.0C for 4 min., ramp 20C/min. to 100C, hold ITGCnraCjarenrcHitseofererarGdTLaePsimnr:eepseTsruearmteu:preer:ature: IIInnnjjjeeeccctttiiiooonnn MLPuinoredgree::Delay: 2H24mr5S22ee2p0pmmilm0nilsuiCim.atin,Cmlifen.roIsadDrsme0rps.t2or-5fa8ti0mghheiptnasg.in,/lmaaralsiysmnti.pctao8l03rup0nsp.i/smi,ihno. ltdoa6t03p0spi,shi ofoldr 0.5 Exygen Research Page 16 of 217 : 533 : MIN 313/023622 Exygen Study No.: 023-076 Purge Flow to Split Vent: 10 mL/min. IEnlejeccttrioonnMVoullutimplei:er Voltage: F1rmomL ATUNE + 200V MScoannitMoroedde:Ions: mSI/Mz's 69 (quantitation ion); 131-, 219 (qualifier ions) DInwteeglrlaTtoirm: e: 7H5ewmlsett-Packard ChemStation softwa_re iT\goitgailiuruunutime: ~7 minutes--_T ^ ItlniliinlUnltVaOc 6.6.1 PFOA and PFOS Quantitation and Example Calculation FTlcionihfneetceapeernnetarrmkeagtiarciroerensoaslwiiwoteanars)ssdmboeyfteeasrsAamumnrineapdlelyedastnofrrdoscomthaftletwihbsaertaraenetqidouaunarstdisinotcagnunsrdsvbaiexerldwocwawos.negrceeennietnrrjaaettcietodends(uinsoitnfogstt1ha/enxdLfaiCtrd/wMse. Sig/hMTtehSde. Etpnhrgqeo/umgasrLttaiamonfnod. ra1rTsdechraeulcncmuurElvaaqentuedda(ultitirnohienneaera2. mcroaeulgcrnuetlsaostifeodanntaphleayrtaeammfooeuutennrdts)o(ifgneannngear/lmyattLeed,fobbuaynseddthineonnAgpn/egaalkyfosartrelsiaov)feturwsaainnrgde Equation 1: Where: AF = Analyte found Aliquot Factor (ng/mL) = (Peaksalorpeae - intercept) x AF EAqnuaalytitoenfo2u:nd (ppb, ng/g for liver andng/mL for serum and urine) = Where: DFVF == DFiinluatlioVnolFuamcsaatenomarlp,lfeovuonld. ((mngL/m) oLr-)sxamFpVle(mwLei)gxhtD(Fg) EFoqruastaiomnp3lecsalfcourltaiftieeddthweitpherkcennotwrnecoavmeroyu.nts of PFOA and PFOS prior to extraction, ERqeucoavtieorny3(:%) = ((anal, found a(pmpobu)n-taavdgd.eadn(apl,pibn)Ctrl (ppbfi xl00% An example of a calculation using an actual sample follows (for PFOS only): Exygen Research Page 17 of 217 : 534 : MIN 313/023622 Exygen Study No.: 023-076 Rat liver sample Exygen ID 0201684 Spk A (Set: 0100802B), fortified at 10 ng/g where: pisnleotaepkrecaerpeta === 5316502.1280.7047 - pdpilbutaiodndefdac(tfoorrt level) == 110 . ... faasiavlnimgqa.ulpdovlietonflwtuaicemntigoechrotntrols 2 mL 10 1.0 g' From eAqunaatlyiotenf1o:und (ng/mL) = 156210-1385.0.270741 x 10 = 5.17 ng/mL From eAqunaatlyiotenf2o:und (ppb) = (5.17 ng/m(1L-0xg)2 mL x 1) From e%quRateicoonve3r:y = = 10.3 ppb ((10.3 p1p0bp-pbOppb) x 100% = 103% 6.6.2 POSF Quantitation and Example Calculation OGwstaenCnieg/dMhmatrSeid.ldlsi.TlliithTneeehraeporecfaorkhnegecaaerrndeestsasrpiwaaotcnaioes)nmobwfyeaatHhssuedPreestadCemrhamenpmdlienstethodaertfisrcotoanamlnibdstroahafrettdwioecaqnururesavttaeuinoswndinaasgsrbdgefeilwvonweaesr.caiotnenjdceec(nutetsdrinatigniot1no/sxthfoietf Etlsihovqefeutrwastataianronedndppa1rrgodc/mgarlccLauumrflvao.erteTsd(ehlritenuhnemeaEaraqmnrudoeaugtunirroetinnsosei2f.oancnaalpclayurtleaamtfeoedutentrhdse)(iangmepnogeur/nmattLeod,fbabanysaeldtyhtoeenfHopuPenadkCiahnreempa)gst/uagstiifnoongr Equation 1: Where: DF = Analyte found Dilution Factor (pg/mL) = (Peakslaorpeae - intercept! x DF Exygen Research Page 18 of 217 : 535 : MIN 313/023622 : 536 : MIN 313/023622 Exygen Study No.: 023-076 Note: This example calculation was done using rounded numbers, and therefore may be slightly different from the values shown in the RAW DATA. 7.0 EXPERIMENTAL DESIGN bEkmcaolnnaaenaocntchlwhkyeon,snsdittescwrtaoaonnotcidcofmoenntsnahssattie,rrmsnoiatxepntadilbeonelnsfaaiolneay(flknlzdisdevodesf~naorimern2ot0pirdfmliuseesaapedfmrtloriuarcpitmxtaliketf)eisneb..fodlowaEErannaatkLccac,hhCokn/sstnMaewcotemSownop/tnMfrlmeascSatoawimnotaarcnpisnexslan,eelxtsoyrbtnsa(rlileaatsiivncoftecikneerosdlnadonusrfisdsosasirtn~emetrgidupf1it0mleohedsef)faofaomorapnrttppeifGlriekomesCpdn.ar/oMtaiwratitSnxae 8.0 RESULTS TITlciIoshaIrte.berdlePesTFspihOonIenVSdTP-ifVnaFobguIO.lntAeodsTtifhhnoVeeutInahIPn-edOIacXliSoyn.FntettrfhroPoeeuletencarnaokdttnsiitolnirnvwoetlterhirm,reeasetcesnorl.ouinvtmterro,d,laenstreeadcrttuuelmridvin,eerian,nssadaemrnuupyrmlieno,sefaasnrtahedmeluipsrctlieoensdnetairsnroaelmTlaspiasbltemlesedpsaleirInseIndividual recoveries for PFOS in the rat liver, serum, and urine samples are detailed in Tables X-XII. The average percent recoveries standard deviations for PFOS in rat liver, serum, and urine samples were 96% 11%, 102% 14%, and 87% 11%, respectively. Individual recoveries for PFOA in the rat liver, serum, and urine samples are detailed in Tables XIII-XV. The average percent recoveries standard deviations for Tr1,7rn%/u-v ,a. rienspreacit!liivv__ee_l_ry_,. s__e_rI__nu__dm_i,via_d_n_u_uai l_u__nr:en__ce_o__vs__ae_m_r_i_e_psil-e_fso_wr___e_Pr__OenySnyF-/oijn.jlntynh-fe/o,r1airtu\cjnli)v/oe_ir_jl,iiastedwr/-u,m--a,uAuan1 udi nuouTMf-rixnjel samples are detailed in Tables XVI-XVIII. The average percent recoveries standard deviations for POSF in rat liver, serum, and urine samples were 99% 18%, 92% 18%, and 99% 18%, respectively. PInnXnooFXdnOPiI-vSO.dideSPitunFeFactOldtherSeedetrseilanucettlvttelsheidvleaseirnrrteaotaslain8ssmey2tre7poud0lfmeintsnhsgreTa/agmran.abgptIelllenedivsdXfeirrvrIaoiXnsmdag.umenaPdlopFnrflreeO-ossdA.umelttIeinsnncodattnerihvde-eiddllreieusatvtaeteeclldlitrsveeiedtnsorulTels5tavas3meb5all,spr0eelt0eXol0sisX1rnta5e.gnd8/Tgg,i0.ehn0de0Trferanobwgm/lamesL. Individual results are listed in Table XXII. PFOA in the rat serum samples ranged from nwTnraogaann/sbmg-lndeLedoe.XtfPerIXcOontImedSVdiFvn.lieoddvneuPet-aFedllscOerttteSeeodscuit1nieln2tdts,h1alaen0er0yvreaeonltlifsgsut/ttrmehoidenL1eri.n8as,tIa6Tnsm0aed0rpbiuvnlleimegds/XumrsaaaXLlnmVr.gpee.sIldeunPsfldt.FrisovIOnmaidArdueinvialoniildsnrttu-heedadseelutrirlenatecstsTtuuaearlrdteibsnllleeaeivsrstXeeaelmldXsistIpitonIelIed4T.s7ianT1b0hleere Exygen Research Page 20 of 217 : 537 : MIN 313/023622 Exygen Study No.: 023-076 XXVI. There was no POSF detected in any of the rat urine samples. Individual results are listed in Table XXVII. 9.0 CONCLUSIONS * TPFheOSra,tPFlivOeAr, asnedruPmO,SaFnadccuorrindeingsatmo pthleesapwperroeprsiuacteceasnsafulyltliycaelxmtreatchtoedd. and analyzed for 10.0 RETENTION OF DATAAND SAMPLES WREsotinhurxeehcisagheep1ciannt9earar9ctcslih7ohof)epidn,awifsceoitiEisnlrflliaNuottlbmiyfVme-aaes/neMnlpslahteslrCicpyaplitoe/wfpiCcigceciasHddf,liareEtarthdoaeMwo,pitwnoa(hd9rseeatO8vwts)iaeEp1ser,7oClcwln.eoDxsaimloaslPrcpRa.brtlieeesncTtticegaorhi,nieppniteasilaeedelidldssncooeoooerdsffpsiagGyimtninenooopmattofllhepditepnsehLraceEalpoauftxebfuidyrnoregarrdeealefantalfatooeacnrrRgiayeglsielnetyPsnycwetre-eiraiscralpacalcstlethuibeccrbdieeeafspirbt(csoaacuyrnhsrbtaEcirmvawexeensivystdditgseaafeaeodtrnldarel. archived by the sponsor. Exygen Research : 538 : Page 21 of 217 MIN 313/023622 Exygen Study No.: 023-076 TABLES Exygen Research : 539 : Page 22 of 217 MIN 313/023622 Exygen Study No.: 023-076 Table I. Summary of PFOS in Control Rat Liver Samples Sponsor ID Lot#14124 Lot#14124* Lot#14124 Lot#14124* Lot #14124 " Lot #14124* Lot #14124 Lot#14124* Lot#14124 Lot#14124* Exygen ID 0201684 Control A 0201684 Control A 0201684 Control A 0201684 Control A 0201684 Control A 0201684 Control A 0201684 Control A 0201684 Control A 0201684 Control A 0201684 Control A Set Number 100802B 100802B 101402B 101402B 101602A 10162A 101602B 101602B 102102A 102102A PFOS - ND . NndD ND ND ND ND ND ND ND Table II. Summary of PFOS in Control Rat Serum Samples Sponsor ID Lot#07024 Lot#07024* Lot#07024 Lot#07024* Lot #07024 Lot#07024* Lot#07024 Lot#07024* Lot#07024 Lot#07024* Exygen ID 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A Set Number 092002B 092002B 092502A 092502A 092502B 092502B 100102A 100102A 100202A 100202A PFOS Found (ng/mL) ND ND ND ND ND ND ND ND ND ND Table III. Summary of PFOS in Control Rat Urine Samples Sponsor ID Exygen ID Set Number PFOS Found (ng/mL) Lot#07124 Lot#07124* Lot#07124 0201683 0201683 0201683 Lot#07124* 0201683 Lot#07124 0201683 Lot#07124* Lot#07124 00220011668833 N(*0DD.0u0=p0LlN1iocotpa#ttg0eD/7m1Ien2tLe4je)*c)ctetidon(Ar0e2a01l6e8ss3 Control A Control A Control A Control A Control A CCoonnttrrooll AA Control A 100302A 100302A 100702A 100702A 100702B 100702B 102102B 102102B than the lowest concentration of the ND ND ND ND ND ND ND ND calibration standards Exygen Research Page 23 of 217 : 540 : MIN 313/023622 Exygen Study No.: 023-076 Table IV. Summary of PFOA in Control Rat Liver Samples Sponsor ID Lot #14124 Lot #14124* LLoott##1144112244* Lot#14124 Lot#14124* Lot#14124 Lot #14124* Lot#14124 Lot#14124* Exygen ID 0201684 Control A 0201684 Control A 0201684 Control A O0Z2U0116'O8OH/4i Control<n ^U--IIUa.__U1I a A 0201684 Control A 0201684 Control A 0201684 Control A 0201684 Control A 0201684 Control A Set Number 100802B 100802B 101402A 1m a no a 101602A 10162A 101602B 101602B 102102A 102102A PFOA ' ND _ ND ND NDxINr ir-\/ ND ND ND ND ND Table V. Summary of PFOA in Control Rat Serum Samples Sponsor ID Lot#07024 Lot#07024* Lot #07024 Lot #07024* Lot#07024 Lot#07024* Lot#07024 Lot#07024* Lot #07024 Lot #07024* Exygen ID 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A 0201682 Control A Set Number 092002B 092002B 092502A 092502A 092502B 092502B 100102A 100102A 100202A 100202A PFOA Found (ng/mL) ND ND ND ND ND ND ND ND ND ND Table VI. Summary of PFOA in Control Rat Urine Samples Sponsor Exygen Set PFOA ID ID Number Found (ng/mL) Lot#07124 Lot#07124* 0201683 Control A 100302A 0201683 Control A 100302A ND ND L o t#07124 Lot#07124* Lot#07124 0201683 Control A 0201683 Control A 0201683 Control A 100702A 100702A 100702B ND ND ND LLoott##0077112244* 0201683 Control A 0201683 Control A 100702B 102102B ND ND N(*0DD.0u0=p0LlN1iocotpa#tgt0eD/7m1Ien2tL4eje)*c)ctetidon(Ar0e2a01l6e8s3s Control A 102102B than the lowest concentration of the ND calibration standards Exygen Research Page 24 of 217 : 541 : MIN 313/023622 Exygen Study No.: 023-076 Table VII. Summary of POSF in Rat Liver Control Samples Sponsor ID Lot#21824 Lot#21824 Lot#21824 Lot #21824 Lot#21824 Lot#21824 Lot#21824 LLoott##2211882244 Lot#21824 Exygen ID 0202877 0202877 0202877 0202877 0202877 0202877 0202877 0202877 0202877 0202877 Set Number 102202A 102302A 102302A 02402A 102402A 102502A 102502A 102802A 102802A 102902A POSF Found (ug/g) ' ND ND NNDD ND ND ND ND ND ND Table VIII. Summary of POSF in Rat Serum Control Samples Sponsor ID Lot#07024 Lot#07024 Lot#07024 Lot #16423 Lot#16423 Lot#16423 Lot#16423 LL0ott##1166442233 Lot#07024 Exygen ID 00220011668822 0201682 00220022998877 0202987 0202987 0202987 0202987 0201682 Set Number 092602B 092702A 100102A 110000230022AA 110000440022AA 100702A 100802A 101702A POSF Found (pg/mL) ND ND ND ND ND ND ND ND ND ND Table IX. Summary of POSF in Rat Urine Control Samples Sponsor ID Exygen ID Set Number POSF Found (pg/mL) Lot#20324 Lot#20324 Lot#20324 Lot#20324 Lot#20324 Lot#20324 Lot#07124 Lot#07124 00220022778855 0202785 0202785 0202785 0202785 0201683 0201683 101002A 110011140022AA 101502A 110012610022AA 102202A 102902A ND ND ND ND ND ND ND ND ND = Not Detected Exygen Research Page 25 of 217 : 542 : MIN 313/023622 Exygen Study No.: 023-076 Table X. Summary of PFOS Fortification Recoveries in Rat Liver Sponsor Exygen Set Amt % ID ID Number Added (ng/g) Recovery Lot#14124 0201684 Spk A 100802B 10 ' 103 Lot#14124 0201684 Spk A* 100802B 10 92 Lot#14124 0201684 SpkB 100802B 50 92 Loi #14124 21 UUlUO*t OpR.o_ i_nD* 0203485 SpkC 100802B11Un Un oOnUo2D.D cn 5000m J\J 21 0203485 SpkC* 100802B ' '5000 88 102 94 Lot#14124 0201684 Spk A 101402B 10 101 Lot#14124 0201684 Spk A* 101402B 10 85 Lot#14124 0201684 SpkB 101402B 50 105 Lot#14124 0201684 SpkB* 101402B 50 105 1 0203465 SpkC 101402B 5000 112 1 0203465 SpkC* 101402B 5000 104 Lot#14124 0201684 Spk A 101602A 10 115 Lot#14124 0201684 Spk A* 101602A 10 100 Lot#14124 0201684 SpkB 101602A 50 95 Lot#14124 0201684 SpkB* 101602A 50 101 42 0203505 Spk C 101602A 50000 94 42 Lot#14124 0203505 SpkC* 0201684 Spk A 101602A 101602B 50000 10 92 104 Lot#14124 0201684 Spk A* 101602B 10 103 Lot#14124 0201684 SpkB 101602B 50 88 Lot#14124 0201684 SpkB* 101602B 50 92 61 0203524 SpkC 101602B 50000 68 61 0203524 SpkC* 101602B 50000 75 Lot#14124 0201684 Spk A 102102A 10 81 Lot#14124 0201684 Spk A* 102102A 10 109 Lot#14124 0201684 SpkB 102102A 50 101 Lot#14124 0201684 SpkB* 102102A 50 97 81 0203543 SpkC 102102A 500000 83 81 0203543 SpkC* 102102A 500000 88 AVERAGE: 96 STANDARD DEVIATION: 11 RELATIVE STANDARD DEVIATION: 11 *Duplicate Injection Exygen Research : 543 : Page 26 of 217 MIN 313/023622 Exygen Study No.: 023-076 Table XI. Summary of PFOS Fortification Recoveries in Rat Serum Sponsor Exygen Set Amt % ID _______________ ID Number Added (ng/mL) Recovery Lot#07024 Lot#07024 0201682 Spk A 0201682 Spk A* 092002B 092002B 10 ' 135 10 _ . 123 Lot#07024 0201682 Spk B 092002B 50 126 Lot #07024 0201682 Spk B* 1M-GROUP 1Day 92 0203367 SpkC 092002B 5J0cUn00 nc 99 IM-GROUP 1Day 92 0203367 SpkC* 092002B 5000 99 Lot#07024 0201682 Spk A 092502A 10 91 Lot#07024 Lot#07024 0201682 Spk A* 092502A 0201682 SpkB 092502A 10 50 74 97 Lot#07024 0201682 SpkB* 092502A 50 110 21F-GROUP 1Day 92 0203387 SpkC 092502A 5000 107 21F-GROUP 1Day 92 0203387 SpkC* 092502A 5000 99 Lot#07024 0201682 Spk A 092502B 10 79 Lot #07024 0201682 Spk A* 092502B 10 98 Lot#07024 0201682 SpkB 092502B 50 99 Lot#07024 0201682 SpkB* 092502B 50 105 41M-GROUP 1Day 121 0203406 Spk C 092502B 5000 112 41M-GROUP 1Day 121 0203406 SpkC* 092502B 5000 107 Lot#07024 0201682 Spk A 100102A 10 101 Lot#07024 0201682 Spk A* 100102A 10 98 Lot#07024 0201682 SpkB 100102A 50 104 Lot#07024 0201682 SpkB* 100102A 50 101 61F-GROUP 1Day 121 0203426 SpkC 100102AR 5000 98 61F-GROUP 1Day 121 0203426 SpkC* 100102AR 5000 95 Lot#07024 0201682 Spk A 100202A 10 101 Lot#07024 0201682 Spk A* 100202A 10 117 Lot#07024 0201682 SpkB 100202A 50 105 Lot#07024 0201682 SpkB* 100202A 50 110 81M-GROUP 1Week 4 0203445 SpkC 100202A 200000 70 81M-GROUP 1Week 4 0203445 SpkC* 100202A 200000 85 AVERAGE: 102 STANDARD DEVIATION: 14 * Duplicate Injection RELATIVE STANDARD DEVIATION: 14 Exygen Research : 544 : Page 27 of 217 MIN 313/023622 Exygen Study No.: 023-076 Table XII. Summary of PFOS Fortification Recoveries in Rat Urine Sponsor ID Lot#07124 Lot#07124 Lot#07124 Lot#07124 -1 1 Lot#07124 Lot#07124 Lot#07124 Lot#07124 24 24 Lot#07124 Lot#07124 Lot#07124 Lot#07124 44 44 Lot#07124 Lot#07124 Lot#07124 Lot#07124 64 64 Exygen Set Amt % ID Number Added (ng/mL) Recovery 0201683 Spk A 100302A 10 ' 87 0201683 Spk A* 100302A 0201683 SpkB 100302A 0201683 SpkB* 100302A 0203563 Spk C 100302AR 0203563 Spk C* 0201683 Spk A 100302AR 100702A 0201683 Spk A* 100702A 0201683 SpkB 100702A 0201683 SpkB* 0203586 SpkC 100702A 100702A 0203586 Spk C* 0201683 Spk A 0201683 Spk A* 100702A 100702B 100702B 10 50 50 ( .500 500 10 10 50 50 500 500 10 10 84 84 88 110 105 88 83 89 74 97 95 88 99 0201683 SpkB 100702B 50 88 0201683 SpkB* 100702B 0203606 Spk C 100702B 50 500 82 99 0203606 SpkC* 0201683 Spk A 0201683 Spk A* 0201683 SpkB 0201683 SpkB* 0203625 Spk C 0203625 SpkC* 100702B 102102B 102102B 102102B 102102B 102102B 102102B 500 10 10 50 50 1000 1000 99 71 72 88 67 78 76 AVERAGE: 87 STANDARD DEVIATION: 11 RELATIVE STANDARD DEVIATION: 13 * Duplicate Injection Exygen Research : 545 : Page 28 of 217 MIN 313/023622 Exygen Study No.: 023-076 Table XIII. Summary of PFOA Fortification Recoveries in Rat Liver Sponsor Exygen Set Amt % ID ID Number Added (ng/g) Recovery Lot#14124 0201684 Spk A 100802B Lot#14124 0201684 Spk A* 100802B Lot#14124 Lot#14124 21 21 0201684 Spk B 0201684 Spk B* 0203485 Spk C 0203485 SpkC* 100802B 100802B 100802B 100802B Lot #14124 Lot#14124 0201684 Spk A 0201684 Spk A* 101402A 101402A Lot#14124 0201684 Spk B 101402A Lot#14124 0201684 SpkB* 101402A 1 0203465 SpkC 101402A 1 Lot#14124 Lot#14124 0203465 Spk C* 0201684 Spk A 0201684 Spk A* 101402A 101602A 101602A Lot#14124 0201684 SpkB 101602A Lot#14124 0201684 SpkB* 101602A 42 42 Lot#14124 0203505 SpkC 0203505 Spk C* 0201684 Spk A 101602A 101602A 101602B Lot#14124 0201684 Spk A* 101602B Lot#14124 Lot#14124 0201684 SpkB 0201684 SpkB* 101602B 101602B 61 0203524 SpkC 101602B 61 Lot #14124 Lot#14124 Lot#14124 0203524 Spk C* 0201684 Spk A 0201684 Spk A* 0201684 SpkB 101602B 102102A 102102A 102102A Lot#14124 0201684 SpkB* 102102A 81 81 0203543 Spk C 0203543 Spk C* 102102A 102102A 10 ' 109 10 102 50 96 50 5000 18091 5000 101 10 114 10 99 50 104 50 94 5000 96 5000 98 10 103 10 111 50 97 50 100 50000 97 50000 92 10 101 10 104 50 93 50 92 50000 83 50000 10 82 106 10 121 50 106 50 108 520000 84 520000 83 AVERAGE: 99 STANDARD DEVIATION: 9 * Duplicate Injection RELATIVE STANDARD DEVIATION: 9 Exygen Research : 546 : Page 29 of 217 MIN 313/023622 Exygen Study No.: 023-076 Table XIV. Summary of PFOA Fortification Recoveries in Rat Serum Sponsor Exygen Set Amt % ID _________ ID Number Added (ng/mL) Recovery Lot#07024 0201682 Spk A 092002B Lot#07024 0201682 Spk A* 092002B 10 ' 111 10 - 115 Lot#07024 Lot#07024 0201682 SpkB 092002BR 0201682 SpkB* 092002BR 50 50 142 140 1M-GROUP 1Day 92 0203367 SpkC 092002B . 5000 120 1M-GROUP 1Day 92 0203367 SpkC* 092002B 5000 120 Lot#07024 0201682 Spk A 092502A 10 89 Lot#07024 0201682 Spk A* 092502A 10 94 Lot#07024 0201682 SpkB 092502A 50 96 Lot#07024 0201682 SpkB* 092502A 50 100 21F-GROUP 1Day 92 0203387 SpkC 092502A 21F-GROUP 1Day 92 0203387 SpkC* 092502A 5000 5000 101 100 Lot#07024 0201682 Spk A 092502B 10 91 Lot#07024 0201682 Spk A* 092502B 10 88 Lot#07024 0201682 SpkB 092502B 50 107 Lot#07024 0201682 SpkB* 092502B 50 113 41M-GROUP 1Day 121 0203406 SpkC 41M-GROUP 1Day 121 0203406 SpkC* 092502B 092502B 5000 5000 109 110 Lot #07024 0201682 Spk A 100102A 10 103 Lot#07024 0201682 Spk A* 100102A 10 103 Lot#07024 0201682 SpkB 100102A 50 104 Lot#07024 0201682 SpkB* 100102A 50 105 61F-GROUP 1Day 121 0203426 SpkC 100102AR 5000 79 61F-GROUP 1Day 121 0203426 SpkC* Lot#07024 0201682 Spk A 100102AR 100202A 5000 10 81 102 Lot#07024 0201682 Spk A* 100202A 10 102 Lot#07024 0201682 SpkB 100202A 50 106 Lot#07024 0201682 SpkB* 100202A 50 108 AVERAGE: 105 STANDARD DEVIATION: 14 * Duplicate Injection RELATIVE STANDARD DEVIATION: 14 Exygen Research : 547 : Page 30 of 217 MIN 313/023622 Exygen Study No.: 023-076 Table XV. Summary of PFOA Fortification Recoveries in Rat Urine Sponsor Exygen Set Amt % ID ID Number Added (ng/mL) Recovery Lot#07124 0201683 Spk A 100302A Lot#07124 Lot#07124 0201683 Spk A* 0201683 SpkB 100302A 100302A Lot#07124 0201683 SpkB* 100302A 1 1 0203563 Spk C 100302A 0203563 Spk C* 100302A Lot#07124 Lot#07124 Lot#07124 Lot#07124 24 24 0201683 Spk A 00220011668833SSppkkAB* 0201683 SpkB* 0203586 SpkC 0203586 SpkC* 100702A 100702A 100702A 100702A 100702A 100702A Lot#07124 0201683 Spk A 100702B Lot#07124 0201683 Spk A* 100702B Lot#07124 Lot#07124 44 44 0201683 SpkB 0201683 SpkB* 0203606 SpkC 0203606 Spk C* 100702B 100702B 100702B 100702B Lot#07124 Lot#07124 Lot#07124 Lot#07124 64 0201683 Spk A 00220011668833SSppkkAB* 0201683 SpkB* 0203625 SpkC 102102B 102102B 102102B 102102B 102102B 64 0203625 Spk C* 102102B , 10 10 50 50 -500 500 10 10 50 50 500 500 10 10 50 50 500 500 10 10 50 50 1000 1000 96 102 130 123 80 82 105 103 123 118 110032 103 106 129 126 106 108 130 133 130 130 89 86 AVERAGE: 110 STANDARD DEVIATION: 17 * Duplicate Injection RELATIVE STANDARD DEVIATION: 15 Exygen Research : 548 : Page 31 of 217 MIN 313/023622 Exygen Study No.: 023-076 Table XVI. Summary of POSF Fortification Recoveries in Rat Liver Sponsor Exygen Set Amt % ID____________ID Number Added (ng/g) Recovery Lot#21824 10 Lot#1201824 . 1111 Lot#21824 21 21 Lot#21824 32 32 Lot#21824 42 42 Lot#21824 5522 Lot#6221824 62 Lot#21824 73 Lot#7231824 83 83 Lot#21824 93 93 0202877 Spk A 0203474 SpkB 0203474 Spk C 00220032487757 SSppkkBA 0203475 Spk C 0202877 Spk A 0203485 SpkB 0203485 Spk C 0202877 Spk A 0203495 SpkB 0203495 SpkC 0202877 Spk A 0203505 SpkB 102202A 110022220022AA 102302A 102302A 102302A 102302A 110022330022AA 102402A 102402A 102402A 102402A 102402A 0203505 Spk C 102402A 0202877 Spk A 102502A 0203515 SpkB 102502A 0203515 SpkC 102502A 0202877 Spk A 0203525 SpkB 110022550022AA 0203525 SpkC 0202877 Spk A 0203535 SpkB 110022580022AA 102802A 0203535 SpkC U2U28// SpKA 0203545 SpkB 0203545 SpkC 0202877 Spk A 0203555 SpkB 11002288022A 102802A 102802A 102902A 102902A 0203555 SpkC 102902A 5 ' 106 5 106 5 117 5 115 5 133 5 126 5 120 5 120 5 5 9632 5 5 5 19091 91 5 83 5 90 5 130 5 118 5 119 5 95 5 83 5 85 5 87 5 102 5 5 5 18040 85 5 55 7872 79 5 76 AVERAGE: 99 STANDARD DEVIATION: 18 RELATIVE STANDARD DEVIATION: 19 Exygen Research : 549 : Page 32 of 217 MIN 313/023622 : 550 : MIN 313/023622 Exygen Study No.: 023-076 Table XVIII. Summary of POSF Fortification Recoveries in Rat Urine Sponsor ID Lot#20324 1 1 Lot#20324 _ 11 11 Lot#20324 2244 Lot#20324 43 43 Lot#20324 64 64 Lot#20324 75 75 Lot#3047124 34 Lot#07124 51 51 Exygen Set Amt % ID Number Added (pg/mL) Recovery 0202875 Spk A 0203563 SpkB 0203563 SpkC 101002A 101002A 101002A 0202875 Spk A 0203573 SpkB 0203573 SpkC 00220023857856 SSppkkBA 110011110022AA 101102A 101402A 101402A 0203586 SpkC 00220023867055 SSppkkBA 101402A 101502A 101502A 0203605 SpkC 0202875 Spk A 0203625 SpkB 0203625 SpkC 0202875 Spk A 000222000133666833366 SSSpppkkkBAC 101502A 101602A 101602A 101602A 102102A 102102A 102102A 102202A 0203596 SpkB 102202A 0203596 SpkC 102202A 0201683 Spk A 102902A 0203613 SpkB 102902A 0203613 SpkC 102902A 5' 5 5 5 .5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 . A5VkAGE: 115 124 115 111222313 78 115 112 82 119 103 77 107 104 91 93 64 71 93 83 88 91 90 99 STANDARD DEVIATION: 18 RELATIVE STANDARD DEVIATION: 18 Exygen Research : 551 : Page 34 of 217 MIN 313/023622 Exygen Study No.: 023-076 Table XIX. Summary of PFOS Residues in Rat Liver Samples Sponsor ID 1 1* 2 2* 3 3* 44* 5 5* 6 6* 7 7* 8 8* 99* 10 10* 11 11* 12 12* 13 13* 14 14* 15 15* 16 16* 17 17* 18 18* 19 19* 20 20* Exygen ID 0203465 0203465 0203466 0203466 0203467 0203467 0203468 0203468 0203469 0203469 0203470 0203470 0203471 0203471 0203472 0203472 0203473 0203473 0203474 0203474 0203475 0203475 0203476 0203476 0203477 00220033447778 0203478 0203479 0203479 0203480 0203480 00220033448811 0203482 0203482 0203483 00220033448834 0203484 Set Number 101402B 101402B 101402B 101402B 101402B . 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B 101402B PFOS Found (ng/g) '' 178 196 173 162 225 234 198 216 269 372 44700 46500 49400 40300 62000 58200 38200 36800 39900 37200 110000 105000 101000 104000 122000 114000 126000 127000 91800 86200 352000 318000 250000 216000 238000 229000 297000 226139000000 212000 * Duplicate Injection ND = Not Detected (Area less than lowest calibration standard of 0.0001 jig/mL) Exygen Research Page 35 of 217 : 552 : MIN 313/023622 Exygen Study No.: 023-076 Table XIX (cont'). Summary of PFOS Residues in Rat Liver Samples Sponsor ID 21 21* 22 22* 24 24* 25 25* 26 26* 27 27* 28 28* 29 29* 30 30* 31 31* 32 32* 33 33* 34 34* 35 35* 36 36* 37 37* 38 38* 39 39* 40 40* Exygen ID 0203485 0203485 0203486 0203486 0203487 0203487 0203488 0203488 0203489 0203489 0203490 0203490 0203491 0203491 0203492 0203492 0203493 0203493 0203494 0203494 0203495 0203495 0203496 0203496 0203497 0203497 0203498 0203498 0203499 0203499 0203500 0203500 0203501 0203501 0203502 0203502 0203503 0203503 Set Number 100802B 100802B 100802B 11Q00Q880Q22BB 100802B ' 100802B 100802B 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 1008U2BK 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR 100802BR PFOS Found (ng/g) - 282 296. 284 270 294 296 163 126 92500 90000 71700 68100 74300 66000 82800 91600 60900 56600 227000 216000 146000 145000 181000 169000 2U6UUU 196000 253000 242000 575000 501000 224000 257000 359000 393000 340000 356000 286000 277000 * Duplicate Injection ND = Not Detected (Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 36 of 217 : 553 : MIN 313/023622 Exygen Study No.: 023-076 Table XIX (cont')- Summary of PFOS Residues in Rat Liver Samples Sponsor ID 41 41* 42 /lO* 43 43* 44 44* 45 45* 46 46* 47 47* 48 48* 49 49* 50 50* 51 51* 52 52* 53 53* 5544* 55 55* 56 56* 57 57* 58 58* 59 59* 6600* Exygen ID 0203504 0203504 0203505 0203506 0203506 0203507 0203507 0203508 0203508 0203509 0203509 0203510 0203510 0203511 0203511 0203512 0203512 0203513 0203513 0203514 0203514 0203515 0203515 0203516 0203516 0203517 0203517 0203518 0203518 0203519 0203519 0203520 0203520 0203521 0203521 0203522 0203522 0203523 0203523 Set Number 100802BR 100802BR 110011660022AA 101602A 101602A 101602A 101602A 101602A 101602A 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR 101602AR PFOS Found (ng/g) ' 1790 1720 281 313 183 166 123 123 106 103 30000 30900 28500 28300 45900 45100 48300 45700 26700 27700 92600 95500 81500 75900 61400 57400 83200 90400 107000 97600 234000 220000 140000 124000 196000 200000 236000 257000 149000 158000 N*DDu=pNliocattDeeItnejcetcetdio(nArea less than lowest calibration standard of 0.0001 |ig/mL) Exygen Research Page 37 of 217 : 554 : MIN 313/023622 Exygen Study No.: 023-076 Table XIX (cont'). Summary of PFOS Residues in Rat Liver Samples Sponsor ID 61 61* 62 62* 64 64* 65 65* 66 66* 67 67* 68 68* 69 69* 70 70* 71 71* 72 72* 73 73* 74 74* 75 75* 76 76* 77 77* 78 78* 79 79* 80 80* Exygen ID 0203524 0203524 0203525 0203525 0203526 0203526 0203527 0203527 0203528 0203528 0203529 0203529 0203530 0203530 0203531 0203531 0203532 0203532 0203533 0203533 0203534 0203534 0203535 0203535 0203536 0203536 0203537 0203537 0203538 0203538 0203539 0203539 0203540 0203540 0203541 0203541 0203542 0203542 Set Number 101602B 101602B 101602B 101602B 101602B . 101602B 101602B 101602B 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR 101602BR PFOS Found (ng/g) 155 149 121 122 159 156 136 111 44600 58200 26000 28400 33100 32900 41100 40300 32000 29300 93700 101000 150000 141000 108000 116000 116000 124000 89900 79700 158000 166000 172000 189000 224000 252000 163000 187000 243000 248000 N*DDu=plNicoatteDIentejecctteidon(Area less than lowest calibration standard of 0.0001 (ig/mL) Exygen Research Page 38 of 217 : 555 : MIN 313/023622 Exygen Study No.: 023-076 Table XIX (coni'). Summary of PFOS Residues in Rat Liver Samples lonsor Exygen Set PFOS ID ID Number Found (ng/g) 81 81* 82 82* 83 83* 84 84* 85 85* 86 0203543 0203543 0203544 0203544 0203545 0203545 0203546 0203546 0203547 0203547 0203548 102102A 102102A 102102A 102102A 102102A. 102102A 102102A 102102A 102102A 102102A 102102AR ' 60.9 51.3 59.0 58.3 137 125 50.3 84.0 77.6 86.4 173000 86* 87 87* 88 88* 89 89* 90 90* 91 91* 92 92* 93 93* 94 94* 95 95* 96 96* 97 97* 98 98* 99 0203548 0203549 0203549 0203550 0203550 0203551 00220033555512 0203552 0203553 0203553 0203554 0203554 0203555 0203555 0203556 0203556 0203557 0203557 0203558 0203558 0203559 0203559 0203560 0203560 0203561 102102AR 102102AR 102102AR 102102AR 102102AR 102102AR 102102AR 102102AR 102102AR 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102AR 102102AR 102102AR 102102AR 102102AR 102102AR 102102AR 179000 214000 219000 153000 159000 134000 134000 175000 179000 599 632 1030 1110 44.2 57.4 75.3 72.7 23.2 17.6 209000 174000 150000 137000 204000 228000 182000 9190*0 100* 0203561 0203562 0203562 110022110022AARR 102102AR 119430000000 135000 N* DDu=plNicoatteDIentejecctetidon(Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 39 of 217 : 556 : MIN 313/023622 Exygen Study No.: 023-076 Table XX. Summary of PFOA Residues in Rat Liver Samples Sponsor Exygen Set PFOA ID___________ ID__________ Number__________ Found (ng/g) 1 1* 0203465 0203465 101402A 101402A 2 2* 3 3* 0203466 0203466 0203467 0203467 101402A 101402A 101402A101402A 44* 5 5* 6 6* 7 7* 8 8* 0203468 0203468 0203469 0203469 0203470 0203470 0203471 0203471 0203472 0203472 101402A 101402A 101402A 101402A 101402A 101402A 101402A 101402A 101402A 101402A 99* 10 10* 0203473 0203473 0203474 0203474 101402A 101402A 101402A 101402A 11 11* 12 12* 13 13* 14 14* 15 15* 16 16* 0203475 0203475 0203476 0203476 0203477 0203477 0203478 0203478 0203479 0203479 0203480 0203480 101402A 101402A 101402A 101402A 101402A 101402A 101402A 101402A 101402A 101402A 101402A 101402A 17 17* 18 18* 19 19* 20 20* 0203481 0203481 0203482 0203482 0203483 00220033448834 0203484 101402A 101402A 101402A 101402A 101402A 101402A 101402A 101402A 118 118125 126 168 169 109 104 175 172 1330 1350 1480 1530 1590 1570 657 653 1230 1210 2840 2620 2570 2820 2970 23832200 3360 1790 1770 6960 6970 5850 5570 5210 5070 6200 65325200 5320 N* DDu=plNicoatteDIentejecctetidon(Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 40 of 217 : 557 : MIN 313/023622 Exygen Study No.: 023-076 Table XX (cont'). Summary of PFOA Residues in Rat Liver Samples Sponsor ID 21 21* 22 22* 24 24* 25 25* 26 26* 27 27* 28 28* 29 29* 30 30* 31 31* 32 32* 33 33* 34 34* 35 35* 36 36* 37 37* 38 38* 39 39* 40 40* Exygen ID 0203485 0203485 0203486 0203486 0203487 0203487 0203488 0203488 0203489 0203489 0203490 0203490 0203491 00220033449912 0203492 0203493 0203493 0203494 0203494 0203495 0203495 0203496 0203496 0203497 0203497 0203498 0203498 0203499 0203499 0203500 0203500 00220033550011 0203502 0203502 0203503 0203503 Set Number 100802B 100802B 100802B 100802B 100802B . 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B 100802B PFOA Found (ng/g) 23.2 32:7 36.5 35.3 38.8 39.8 30.4 26.1 29.1 28.5 34.7 44.9 34.3 31.4 41.2 51.1 34.9 33.5 39.5 40.1 31.2 34.5 37.5 39.9 44.8 41.3 39.9 44.9 95.1 103 58.8 56.6 53.6 49.1 61.1 54.9 44.0 41.0 * Duplicate Injection ND = Not Detected (Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 41 of 217 : 558 : MIN 313/023622 Exygen Study No.: 023-076 Table XX (cont'). Summary of PFOA Residues in Rat Liver Samples Sponsor ID 4411* 42 42* . 43 43* 44 44* 45 45* 46 46* 47 47* 48 48* 49 49* 50 50* 51 51* 52 52* 53 53* 54 54* 55 55* 56 56* 57 57* 58 58* 59 5690* 60* Exygen ID 0203504 0203504 0203505 0203505 0203506 0203506 0203507 0203507 0203508 0203508 0203509 0203509 0203510 0203510 0203511 0203511 0203512 0203512 0203513 0203513 0203514 0203514 0203515 0203515 0203516 0203516 0203517 0203517 0203518 0203518 0203519 0203519 0203520 0203520 0203521 0203521 0203522 0203522 0203523 0203523 Set Number 100802B 100802B 101602A 101602A 101602A. 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A 101602A PFOA Found (ng/g) ' 68.0 68.4 77.5 82.9 63.1 74.6 44.4 44.5 58.3 52.1 194 176 351 355 295 293 417 439 433 420 672 645 388 381 489 482 216 214 574 564 938 930 408 392 349 340 272 267 357 366 N*DDu=pNliocattDeeItnejcetcetdio(nArea less than lowest calibration standard of 0.0001 (ig/mL) Exygen Research Page 42 of 217 : 559 : MIN 313/023622 Exygen Study No.: 023-076 Table XX (cont'). Summary of PFOA Residues in Rat Liver Samples Sponsor ID 61 61* 62 6624* 64* 65 65* 66 66* 67 67* 68 68* 69 69* 70 70* 71 71* 72 72* 73 73* 74 74* 75 75* 76 76* 77 77* 78 78* 79 79* 80 80* Exygen ID 0203524 0203524 0203525 0203525 0203526 0203526 0203527 0203527 0203528 0203528 0203529 0203529 0203530 0203530 0203531 0203531 0203532 0203532 0203533 0203533 0203534 0203534 0203535 0203535 0203536 0203536 0203537 0203537 0203538 0203538 0203539 0203539 0203540 0203540 0203541 0203541 0203542 0203542 Set Number 101602B 101602B 101602B 101602B 101602B _ 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B 101602B PFOA Found (ng/g) 34.0 36.3 23.5 20.7 22.6 ND 27.5 22.0 26.6 20.9 20.4 19.7 28.7 29.7 21.9 24.0 33.4 34.7 20.8 18.8 ND 25.7 27.3 34.1 27.3 32.6 25.1 19.4 19.6 27.0 21.2 21.5 ND ND 31.6 30.0 28.7 29.6 * Duplicate Injection ND = Not Detected (Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 43 of 217 : 560 : MIN 313/023622 Exygen Study No.: 023-076 Table XX (coni'). Summary of PFOA Residues in Rat Liver Samples * OO oo Sponsor ID 81 81* 82 82* 83 83* 84 84* 85 85* 86 86* 87 87* 88 89 89* 90 90* 91 91* 92 92* 93 93* 94 94* 95 95* 96 96* 97 97* 98 98* 99 99* 100 100* Exygen ID 0203543 0203543 0203544 0203544 0203545 0203545 0203546 0203546 0203547 0203547 0203548 0203548 0203549 0203549 0203550 0203550 0203551 0203551 0203552 0203552 0203553 0203553 0203554 0203554 0203555 0203555 0203556 0203556 0203557 0203557 0203558 0203558 0203559 0203559 0203560 0203560 0203561 00220033556612 0203562 Set Number 102102A 102102A 102102A 102102A 102102A_ 102102A 102102A 102102A 102102A 102102A 102102AR 102102AR 102102AR 102102AR 102102AR 102102AR 102102AR 102102AR 102102AR 102102AR 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A 102102A PFOA Found (ng/g) 42.0 44.7 40.9 43.2 47.9 44.3 41.5 44.6 61.7 54.0 5750 5950 7320 6950 5680 5590 7530 7450 8250 8270 60.4 56.7 79.3 81.9 ND ND ND ND ND ND 26.3 24.8 21.9 19.2 25.7 29.2 19.6 ND 24.2 24.1 * Duplicate Injection ND = Not Detected (Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 44 of 217 : 561 : MIN 313/023622 Exygen Study No.: 023-076 Table XXI. Summary of POSF Residues in Rat Liver Samples Sponsor ID 11* 2 . 23* 3* 44* 5 5* 6 6* 7 7* 88* 99* 1100* 1111* 12 12* 13 13* 14 14* 15 15* 16 16* 17 17* 18 18* 19 212090** Exygen ID 0203465 0203465 0203466 0203466 0203467 0203467 0203468 0203468 0203469 00220033446790 0203470 0203471 0203471 0203472 0203472 0203473 00220033447734 0203474 0203475 0203475 0203476 0203476 0203477 0203477 0203478 0203478 0203479 0203479 0203480 0203480 0203481 00220033448812 0203482 0203483 00220033448834 0203484 Set Number 110022220022AA 102202A 110022220022A . 102202A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 110022330022AA 110022330022AA 102302A 102302A 102302A 102302A 102302A 102302A 102302A 102302A 102302A 102302A 102302A 102302A 102302A 102302A 110022330022AA POSF Found (pg/g) ' ND ND ND ND ND ND ND ND ND NNNDDD ND ND NNDD NNDD ND NNDD ND ND ND ND ND ND NNDD ND ND ND ND ND ND ND ND ND NNDD , * Duplicate Aliquot ND = Not Detected (Area less than lowest calibration standard of 25 pg/mL) Exygen Research Page 45 of 217 : 562 : MIN 313/023622 : 563 : MIN 313/023622 Exygen Study No.: 023-076 Table XXI (cont'). Summary of POSF Residues in Rat Liver Samples >onsor Exygen Set ID ID Number POSF Found (ug/g) 41 41* 42 42* 43 43* 44 44* 45 45* 46 46* 47 47* 48 444899** 50 50* 51 51* 52 52* 53 53* 5544* 55 5556* 56* 57 57* 58 555899** 60 60* 0203504 0203504 0203505 0203505 00220033550066 0203507 0203507 0203508 0203508 0203509 00220033550190 0203510 0203511 0203511 0203512 0203512 0203513 0203513 00220033551144 0203515 00220033551156 00220033551176 0203517 0203518 0203518 0203519 0203519 0203520 00220033552210 0203521 0203522 00220033552232 0203523 102402A 102402A 102402A 102402A 102402A . 110022440022AA 110022440022AA 102402A 102402A 102402A 102402A 110022440022AA 110022440022AA 102402A 102402A 102402A 102402A 102402A 102502A 102502A 102502A 102502A 110022550022AA 102502A 102502A 102502A 102502A 102502A 110022550022AA 102502A 102502A 102502A 102502A 102502A ' ND NET ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND NNDD NNDD ND NNDD ND ND NNDD ND ND ND ND ND ND ND ND NNDD ND N*DDu=plNicoatteDAetleicqtueodt(Area less than lowest calibration standard of 25 pg/mL) Exygen Research Page 47 of 217 : 564 : MIN 313/023622 Exygen Study No.: 023-076 Table XXI (cont'). Summary of POSF Residues in Rat Liver Samples Sponsor Exygen Set POSF ID___________ - ID__________ Number__________ Found (pg/g) 61 0203524 102502A ' ND 61* 0203524 102502A ND 62 0203525 102502A ND - 6624* 64* 65 65* 0203525 0203526 0203526 0203527 0203527 102502A 110022550022AA 102502A 102502A NNDD ND ND ND 66 0203528 102502A 66* 0203528 102502A ND ND 67 0203529 102502A 67* 0203529 102502A ND ND 68 0203530 102502A ND 68* 0203530 102502A 667990* 70* 0203531 0203531 0203532 0203532 102502A 102502A 102502A 102502A NNDD ND ND ND 71 0203533 102502A ND 71* 72 72* 0203533 0203534 0203534 102502A 102502A 102502A 73 777344** 75 75* 76 76* 77 0203535 0203535 0203536 0203536 00220033553377 0203538 0203538 0203539 110022880022AA 102802A 102802A 110022880022AA 102802A 102802A 102802A ND ND ND ND ND NNNDDD ND ND ND ND 77* 78 78* 79 79* 0203539 000222000333555444100 0203541 102802A 102802A 102802A 110022880022AA 80 80* 0203542 0203542 102802A 102802A ND ND ND ND ND ND ND * Duplicate Aliquot ND = Not Detected (Area less than lowest calibration standard of 25 pg/mL) Exygen Research Page 48 of 217 : 565 : MIN 313/023622 Exygen Study No.: 023-076 Table XXI (cont'). Summary of POSF Residues in Rat Liver Samples Sponsor ID 81 81* 82 82* - 83 83* 84 84* 8855* 86 8867* 88 88* 89 89* 90 90* 91 91* 9922* 9933* 94 94* 95 9956* 96* 9977* 98 98* 99 99* 100 100* *00 Exygen ID 0203543 000222000333555444344 0203545 0203545 0203546 0203546 0203547 0203547 0203548 0203548 00220033554499 0203550 0203550 0203551 0203551 0203552 0203552 0203553 0203553 0203554 0203554 0203555 00220033555556 0203556 0203557 0203557 0203558 0203558 0203559 00220033555690 0203560 0203561 00220033556612 0203562 Set Number 110022880022AA 102802A 110022880022AA 102802A 102802A 102802A 102802A 102802A 110022880022AA 110022880022AA 102802A 102802A 102802A 102802A 102802A 102802A 102802A 102802A 102802A 102802A 102902A 111000222999000222AAA 102902A 102902A 102902A 102902A 102902A 110022990022AA 102902A 102902A 102902A 102902A 102902A POSF ND ND ND NNDD ND ND ND ND ND ND ND NNDD NNDD ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND NNDD ND NNDD ND * Duplicate Aliquot ND = Not Detected (Area less than lowest calibration standard of 25 fig/mL) Exygen Research Page 49 of 217 : 566 : MIN 313/023622 Exygen Study No.: 023-076 Table XXII. Summary of PFOS Residues in Rat Serum Sample Sponsor ID 1M-GROUP 1Day 92 1M-GROUP 1Day 92* 2M-GROUP 1Day 92 2M-GROUP 1Day 92* - 3M-GROUP 1Day 92 3M-GROUP 1Day 92* 4M-GROUP 1Day 92 4M-GROUP 1Day 92* 5M-GROUP 1Day 92 5M-GROUP 1Day 92* 6M-GROUP 2 Day 92 6M-GROUP 2 Day 92* 7M-GROUP 2 Day 92 7M-GROUP 2 Day 92* 8M-GROUP 2 Day 92 8M-GROUP 2 Day 92* 9M-GROUP 2 Day 92 9M-GROUP 2 Day 92* 10M-GROUP 2 Day 92 10M-GROUP 2 Day 92* 11M-GROUP 3 Day 92 11M-GROUP 3 Day 92* 12M-GROUP 3 Day 92 12M-GROUP 3 Day 92* 13M-GROUP 3 Day 92 13M-GROUP 3 Day 92* 14M-GROUP 3 Day 92 14M-GROUP 3 Day 92* 15M-GROUP 3 Day 92 15M-GROUP 3 Day 92* 16M-GROUP 4 Day 92 16M-GROUP 4 Day 92* 17M-GROUP 4 Day 92 17M-GROUP 4 Day 92* 18M-GROUP 4 Day 92 18M-GROUP 4 Day 92* 19M-GROUP 4 Day 92 19M-GROUP 4 Day 92* 20M-GROUP 4 Day 92 20M-GROUP 4 Day 92* Exygen ID 0203367 0203367 0203368 0203368 0203369 0203369 0203370 0203370 0203371 0203371 0203372 0203372 0203373 0203373 0203374 0203374 0203375 0203375 0203376 0203376 0203377 0203377 0203378 0203378 0203379 0203379 0203380 0203380 0203381 0203381 0203382 0203382 0203383 0203383 0203384 0203384 0203385 0203385 0203386 0203386 Set Number 092002B 092002B 092002B 0920U2B 092002B _ 092002B 092002B 092002B 092002B 092002B 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 009922000022BBRR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR PFOS Found (ng/mL) ' ND NO ND ND ND . ND 50.6 ND 64.7 64.7 6810 6730 6280 6520 5250 5630 8820 8760 5870 5530 23200 23700 24800 23800 23800 23400 20400 20800 19700 22400 102000 107000 98800 98100 98400 87400 110000 104000 55700 55900 N* DDu=plNicoatteDIentejecctetidon(Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 50 of 217 : 567 : MIN 313/023622 Exygen Study No.: 023-076 Table XXII (cont'). Summary of PFOS Residues in Rat Serum Samples Sponsor ID 21F-GROUP 1Day 92 21F-GROUP 1Day 92* 22F-GROUP 1Day 92 -2224FF--GGRROOUUPP11DDaayy9922* 24F-GROUP 1Day 92* 25F-GROUP 1Day 92 25F-GROUP 1Day 92* 26F-GROUP 2 Day 92 26F-GROUP 2 Day 92* 27F-GROUP 2 Day 92 27F-GROUP 2 Day 92* 28F-GROUP 2 Day 92 28F-GROUP 2 Day 92* 29F-GROUP 2 Day 92 29F-GROUP 2 Day 92* 30F-GROUP 2 Day 92 30F-GROUP 2 Day 92* 31F-GROUP 3 Day 92 31F-GROUP 3 Day 92* 32F-GROUP 3 Day 92 32F-GROUP 3 Day 92* 33F-GROUP 3 Day 92 33F-GROUP 3 Day 92* 34F-GROUP 3 Day 92 3345FF--GGRROOUUPP33DDaayy9922* 35F-GROUP 3 Day 92* 36F-GROUP 4 Day 92 36F-GROUP 4 Day 92* 37F-GROUP 4 Day 92 37F-GROUP 4 Day 92* 38F-GROUP 4 Day 92 38F-GROUP 4 Day 92* 39F-GROUP 4 Day 92 39F-GROUP 4 Day 92* 40F-GROUP 4 Day 92 40F-GROUP 4 Day 92* Exygen ID 0203387 0203387 0203388 0203388 0203389 0203389 0203390 0203390 0203391 0203391 0203392 0203392 0203393 0203393 0203394 0203394 0203395 0203395 0203396 0203396 0203397 0203397 0203398 0203398 0203399 0203399 0203400 0203400 0203401 0203401 0203402 0203402 0203403 0203403 0203404 0203404 0203405 0203405 Set Number 092502A 092502A 092502A 092502A 092502A092502A 092502A 092502A 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 100102A 100102A 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR 092502AR PFOS Found (ng/mL) ND NDND ND ND ND ND ND 9270 8700 6350 6320 7980 8750 8480 8450 8760 8990 41500 40200 31100 34900 81300 90400 23900 2454310000 44000 75100 82900 78100 84100 150000 158000 111000 104000 152000 136000 * Duplicate Injection ND = Not Detected (Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 51 of 217 : 568 : MIN 313/023622 Exygen Study No.: 023-076 Table XXII (cont'). Summary of PFOS Residues in Rat Serum Samples Sponsor Exygen ID ID 41M-GROUP 1Day 121 41M-GROUP 1Day 121* 0203406 0203406 42M-GROUP 1Day 121 0203407 42M-GROUP 1Day 121* 43M-GROUP 1Day 121 0203407 0203408 43M-GROUP 1Day 121* 0203408 44M-GROUP 1Day 121 44M-GROUP 1Day 121* 45M-GROUP 1Day 121 0203409 0203409 0203410 45M-GROUP 1Day 121* 46M-GROUP 2 Day 121 46M-GROUP 2 Day 121* 47M-GROUP 2 Day 121 0203410 0203411 0203411 0203412 47M-GROUP 2 Day 121* 48M-GROUP 2 Day 121 48M-GROUP 2 Day 121* 49M-GROUP 2 Day 121 0203412 0203413 0203413 0203414 4590MM--GGRROOUUPP22DDaayy112211* 0203414 0203415 50M-GROUP 2 Day 121* 51M-GROUP 3 Day 121 0203415 0203416 51M-GROUP 3 Day 121* 0203416 52M-GROUP 3 Day 121 52M-GROUP 3 Day 121* 53M-GROUP 3 Day 121 0203417 0203417 0203418 5534MM--GGRROOUUPP33DDaayy112211* 0203418 0203419 54M-GROUP 3 Day 121* 55M-GROUP 3 Day 121 0203419 0203420 55M-GROUP 3 Day 121* 0203420 56M-GROUP 4 Day 121 0203421 56M-GROUP 4 Day 121* 57M-GROUP 4 Day 121 0203421 0203422 57M-GROUP 4 Day 121* 0203422 58M-GROUP 4 Day 121 58M-GROUP 4 Day 121* 59M-GROUP 4 Day 121 59M-GROUP 4 Day 121* 0203423 0203423 0203424 0203424 60M-GROUP 4 Day 121 60M-GROUP 4 Day 121* 00220033442255 Set Number 092502B 092502B 092502B 092502B 092502B . 092502B 092502B 092502B 092502B 092502B 092502BR . 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 092502BR 100202A 100202A PFOS Found (ng/mL) ' NNDD ND ND ND ND ND ND ND ND 6790 6800 7030 7430 4220 4310 4230 4290 2480 2370 11600 10400 18600 17700 24900 2159330000 18800 16500 18000 77300 68700 26800 28700 33700 33100 35800 33700 4479710000 N* DDu=plNicoattDe Ientejecctteidon(Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 52 of 217 : 569 : MIN 313/023622 Exygen Study No.: 023-076 Table XXII (cont')- Summary of PFOS Residues in Rat Serum Samples Sponsor Exygen ID_________ ID 61F-GROUP 1Day 121 0203426 61F-GROUP 1Day 121* 0203426 62F-rGTDRrVOTUTDP11Day110211* 64F-GROUP 1 Day 121vji\vy vjJ. x uj xxx 0203427 0203427 0203428 64F-GROUP 1Day 121* 0203428 65F-GROUP 1Day 121 0203429 65F-GROUP 1Day 121* 0203429 66F-GROUP 2 Day 121 0203430 66F-GROUP 2 Day 121* 0203430 67F-GROUP 2 Day 121 0203431 67F-GROUP 2 Day 121* 0203431 68F-GROUP 2 Day 121 0203432 68F-GROUP 2 Day 121* 0203432 69F-GROUP 2 Day 121 0203433 69F-GROUP 2 Day 121* 0203433 70F-GROUP 2 Day 121 0203434 70F-GROUP 2 Day 121* 0203434 71F-GROUP 3 Day 121 0203435 71F-GROUP 3 Day 121* 0203435 72F-GROUP 3 Day 121 0203436 72F-GROUP 3 Day 121* 0203436 73F-GROUP 3 Day 121 0203437 73F-GROUP 3 Day 121* 0203437 74F-GROUP 3 Day 121 0203438 74F-GROUP 3 Day 121* 0203438 75F-GROUP 3 Day 121 0203439 75F-GROUP 3 Day 121* 0203439 76F-GROUP 4 Day 121 0203440 76F-GROUP 4 Day 121* 0203440 77F-GROUP 4 Day 121 0203441 77F-GROUP 4 Day 121* 0203441 78F-GROUP 4 Day 121 0203442 78F-GROUP 4 Day 121* 0203442 79F-GROUP 4 Day 121 0203443 79F-GROUP 4 Day 121* 0203443 80F-GROUP 4 Day 121 0203444 80F-GROUP 4 Day 121* 0203444 Set Number 100102A 100102A 1in0n0m1092AA 100102A 10002A 100102A 100102A 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR 100102AR PFOS Found (ng/mL) ND ND. 50.9 ND NNDD ND ND 8560 8310 10100 8580 10300 11200 10600 10500 9120 383140000 32700 26100 25700 34300 34300 16500 15400 32900 35600 131000 133000 86000 80800 72900 78300 73900 67300 64700 69200 * Duplicate Injection ND = Not Detected (Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 53 of 217 : 570 : MIN 313/023622 Exygen Study No.: 023-076 Table XXII (cont'). Summary of PFOS Residues in Rat Serum Samples Sponsor Exygen ID _______ ID 81M-GROUP 1Week 4 0203445 81M-GROUP 1Week 4* 0203445 82M-GROUP 1Week 4 0203446 82M-GROUP 1Week 4* 0203446 83M-GROUP 1Week 4 0203447 83M-GROUP 1Week 4* 0203447 84M-GROUP 1Week 4 0203448 84M-GROUP 1Week 4* 0203448 85M-GROUP 1Week 4 0203449 85M-GROUP 1Week 4* 0203449 86M-GROUP 4 Week 4 0203450 86M-GROUP 4 Week 4* 0203450 87M-GROUP 4 Week 4 0203451 87M-GROUP 4 Week 4* 0203451 88M-GROUP 4 Week 4 0203452 88M-GROUP 4 Week 4* 0203452 89M-GROUP 4 Week 4 0203453 89M-GROUP 4 Week 4* 0203453 90M-GROUP 4 Week 4 90M-GROUP 4 Week 4* 0203454 0203454 91F-GROUP 1Week 4 0203455 91F-GROUP 1Week 4* 0203455 92F-GROUP 1Week 4 0203456 92F-GROUP 1Week 4* 0203456 93F-GROUP 1Week 4 0203457 9934FF--GGRROOUUPP11WWeeeekk44* 0203457 0203458 94F-GROUP 1Week 4* 0203458 95F-GROUP 1Week 4 0203459 95F-GROUP 1Week 4* 0203459 96F-GROUP 4 Week 4 0203460 96F-GROUP 4 Week 4* 0203460 97F-GROUP 4 Week 4 0203461 97F-GROUP 4 Week 4* 0203461 98F-GROUP 4 Week 4 0203462 98F-GROUP 4 Week 4* 0203462 99F-GROUP 1Week 4 0203463 99F-GROUP 1Week 4* 0203463 100F-GROUP 1Week 4 100F-GROUP 1Week 4* 0203464 0203464 Set Number 100202A 100202A 100202A 100202A 100202A . 100202A 100202A 100202A 100202A 100202A 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 110000220022ARR 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR PFOS Found (ng/mL) ' ND NE> ND ND ND ND ND ND ND ND 32300 31000 16400 15000 30100 34600 23500 21600 29000 28900 ND ND ND ND ND ND ND ND 522 581 57100 61900 82400 83800 71600 73200 25300 26900 28000 27400 N*DDu=plNicoatteDIentejecctteidon(Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 54 of 217 : 571 : MIN 313/023622 Exygen Study No.: 023-076 Table XXIII. Summary of PFOA Residues in Rat Serum Samples Sponsor Exygen ID____________ ID 1M-GROUP 1Day 92 1M-GROUP 1Day 92* 2M-GROUP 1Day 92 i y z 'utxyr m A r m 1 t~ \___ 3M-GROUP 1Day 92 3M-GROUP 1Day 92* 4M-GROUP 1Day 92 4M-GROUP 1Day 92* 5M-GROUP 1Day 92 5M-GROUP 1Day 92* 6M-GROUP 2 Day 92 6M-GROUP 2 Day 92* 7M-GROUP 2 Day 92 7M-GROUP 2 Day 92* 8M-GROUP 2 Day 92 8M-GROUP 2 Day 92* 9M-GROUP 2 Day 92 9M-GROUP 2 Day 92* 10M-GROUP 2 Day 92 10M-GROUP 2 Day 92* 11M-GROUP 3 Day 92 11M-GROUP 3 Day 92* 12M-GROUP 3 Day 92 12M-GROUP 3 Day 92* 13M-GROUP 3 Day 92 13M-GROUP 3 Day 92* 14M-GROUP 3 Day 92 14M-GROUP 3 Day 92* 15M-GROUP 3 Day 92 15M-GROUP 3 Day 92* 16M-GROUP 4 Day 92 16M-GROUP 4 Day 92* 17M-GROUP 4 Day 92 17M-GROUP 4 Day 92* 18M-GROUP 4 Day 92 18M-GROUP 4 Day 92* 19M-GROUP 4 Day 92 19M-GROUP 4 Day 92* 20M-GROUP 4 Day 92 20M-GROUP 4 Day 92* 0203367 0203367 0203368 U0Z2i0U3J ^3U6O9 0203369 0203370 0203370 0203371 0203371 0203372 0203372 0203373 0203373 0203374 0203374 0203375 0203375 0203376 0203376 0203377 0203377 0203378 0203378 0203379 0203379 0203380 0203380 0203381 0203381 0203382 0203382 0203383 0203383 0203384 0203384 0203385 0203385 0203386 0203386 Set Number 092002B 092002B 01n0/979m422>n00Vn00V22o^ LBBuI 092002B 092002B 092002B 092002B 092002B 092002B 092002B 092002B 092002B 092002B 092002B 092002B 092002B 092002B 092002B 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR 092002BR PFOA Found (ng/mL) ' 60.6 57.3 76.0 71.2 75.5 73.4 78.1 70.7 77.6 84.5 1490 1520 1540 1580 1220 1250 1110 1110 1330 1370 3310 3240 4160 4290 3940 4020 3890 3840 2600 2880 10600 10700 12100 11900 10700 10300 10600 10600 9750 9570 N* DDu=plNicoatteDIentejecctteidon(Area less than lowest calibration standard of 0.0001 |ig/mL) Exygen Research Page 55 of 217 : 572 : MIN 313/023622 Exygen Study No.: 023-076 Table XXIII (conf). SSuammmplaersy of PFOA Residues in Rat Serum Sponsor ID 21F-GROUP 1Day 92 21F-GROUP 1Day 92* 22F-GKUUF I Day 92 22F-GROUP 1Day 92* 24F-GROUP 1Day 92 24F-GROUP 1Day 92* 25F-GROUP 1Day 92 25F-GROUP 1Day 92* 26F-GROUP 2 Day 92 26F-GROUP 2 Day 92* 27F-GROUP 2 Day 92 27F-GROUP 2 Day 92* 28F-GROUP 2 Day 92 28F-GROUP 2 Day 92* 29F-GROUP 2 Day 92 29F-GROUP 2 Day 92* 30F-GROUP 2 Day 92 30F-GROUP 2 Day 92* 31F-GROUP 3 Day 92 31F-GROUP 3 Day 92* 32F-GROUP 3 Day 92 32F-GROUP 3 Day 92* 33F-GROUP 3 Day 92 33F-GROUP 3 Day 92* 34F-GROUP 3 Day 92 34F-GROUP 3 Day 92* 35F-GROUP 3 Day 92 35F-GROUP 3 Day 92* 36F-GROUP 4 Day 92 36F-GROUP 4 Day 92* 37F-GROUP 4 Day 92 37F-GROUP 4 Day 92* 38F-GROUP 4 Day 92 38F-GROUP 4 Day 92* 39F-GROUP 4 Day 92 39F-GROUP 4 Day 92* 40F-GROUP 4 Day 92 40F-GROUP 4 Day 92* Exygen ID 0203387 0203387 0203388 0203388 0203389 0203389 0203390 0203390 0203391 0203391 0203392 0203392 0203393 0203393 0203394 0203394 0203395 0203395 0203396 0203396 0203397 0203397 0203398 0203398 0203399 0203399 0203400 0203400 0203401 0203401 0203402 0203402 0203403 0203403 0203404 0203404 0203405 0203405 Set Number 092502A 092502A 092502A 092502A_ 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 092502A 009922550022AA PFOA Fond (ng/mL) NEX ND INNDI/ ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND 81.7 102 67.6 74.9 ND ND 50.3 51.9 53.8 53.6 * Duplicate Injection Exygen Research Page 56 of 217 : 573 : MIN 313/023622 Exygen Study No.: 023-076 Table XXIII (cont'). SSaummpmleasry of PFOA Residues in Rat Serum Sponsor Exygen Set PFOA _________ ID_____ ID Number Found (ng/mL) 41M-GROUP 1Day 121 41M-GROUP 1Day 121* 42M-GROUP 1Day 121 42M-GROUP 1Day 121* 43M-GROUP 1Day 121 0203406 0203406 U02Z0U3J44 0U7/ 0203408 092502B 092502B u y zju zo 092502B _ 092502B ND ND 'Ji Oo .nJ 38.8 ND 43M-GROUP 1Day 121* 44M-GROUP 1Day 121 44M-GROUP 1Day 121* 45M-GROUP 1Day 121 45M-GROUP 1Day 121* 46M-GROUP 2 Day 121 46M-GROUP 2 Day 121* 47M-GROUP 2 Day 121 47M-GROUP 2 Day 121* 0203408 0203409 0203409 0203410 0203410 0203411 0203411 0203412 0203412 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B ND ND ND 42.6 41.5 486 479 482 502 48M-GROUP 2 Day 121 48M-GROUP 2 Day 121* 49M-GROUP 2 Day 121 49M-GROUP 2 Day 121* 50M-GROUP 2 Day 121 50M-GROUP 2 Day 121* 51M-GROUP 3 Day 121 51M-GROUP 3 Day 121* 0203413 0203413 0203414 0203414 0203415 0203415 0203416 0203416 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 662 678 525 514 519 507 806 619 52M-GROUP 3 Day 121 0203417 52M-GROUP 3 Day 121* 0203417 53M-GROUP 3 Day 121 0203418 53M-GROUP 3 Day 121* 0203418 54M-GROUP 3 Day 121 0203419 54M-GROUP 3 Day 121* 0203419 55M-GROUP 3 Day 121 0203420 55M-GROUP 3 Day 121* 0203420 56M-GROUP 4 Day 121 56M-GROUP 4 Day 121* 57M-GROUP 4 Day 121 0203421 0203421 0203422 57M-GROUP 4 Day 121* 0203422 58M-GROUP 4 Day 121 0203423 58M-GROUP 4 Day 121* 0203423 59M-GROUP 4 Day 121 0203424 59M-GROUP 4 Day 121* 0203424 60M-GROUP 4 Day 121 0203425 N6*0DDMu-=GpRlNicOoaUttPeD4IentDejeaccyttei1do2n1(*Area02le0s3s42t5han 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B 092502B lowest calibration standard 626 604 1160 1160 309 294 790 770 904 917 1030 1040 576 563 328 338 763 776 of 0.0001 pg/mL) Exygen Research Page 57 of 217 : 574 : MIN 313/023622 Exygen Study No.: 023-076 Table XXIII (cont'). SSuammmplaersy of PFOA Residues in Rat Serum Sponsor Exygen _________ ID________ ID 61F-GROUP 1Day 121 0203426 61F-GROUP 1Day 121* 0203426 62F-GROUP 1Day 121 0203427 62F-GROUP 1Day 121* 0203427 64F-GROUP 1Day 121 0203428 64F-GROUP 1Day 121* 0203428 65F-GROUP 1Day 121 0203429 65F-GROUP 1Day 121* 0203429 66F-GROUP 2 Day 121 0203430 66F-GROUP 2 Day 121* 0203430 67F-GROUP 2 Day 121 0203431 67F-GROUP 2 Day 121* 0203431 68F-GROUP 2 Day 121 0203432 68F-GROUP 2 Day 121* 0203432 69F-GROUP 2 Day 121 0203433 69F-GROUP 2 Day 121* 0203433 70F-GROUP 2 Day 121 0203434 70F-GROUP 2 Day 121* 0203434 71F-GROUP 3 Day 121 0203435 71F-GROUP 3 Day 121* 0203435 72F-GROUP 3 Day 121 0203436 72F-GROUP 3 Day 121* 0203436 7 ^ F - m ? n i T P 'K D a y 1 9 1 0203437 73F-GROUP 3 Day 121* 0203437 74F-GROUP 3 Day 121 0203438 74F-GROUP 3 Day 121* 0203438 75F-GROUP 3 Day 121 0203439 75F-GROUP 3 Day 121* 0203439 76F-GROUP 4 Day 121 0203440 76F-GROUP 4 Day 121* 0203440 77F-GROUP 4 Day 121 0203441 77F-GROUP 4 Day 121* 0203441 78F-GROUP 4 Day 121 0203442 78F-GROUP 4 Day 121* 0203442 79F-GROUP 4 Day 121 0203443 79F-GROUP 4 Day 121* 0203443 80F-GROUP 4 Day 121 0203444 80F-GROUP 4 Day 121* 0203444 Set Number 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 1 0 n i0 2 A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A PFOA Found (ng/mL) ND' ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND NNDD ND ND ND ND ND ND ND ND ND ND ND ND * Duplicate Injection ND = Not Detected (Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 58 of 217 : 575 : MIN 313/023622 Exygen Study No.: 023-076 Table XXIII (cont'). Summary of PFOA Residues in Rat Serum Samples Sponsor Exygen Set PFOA _________ ID______________ ID ______Number Found (ng/mL) 81M-GROUP 1Week 4 0203445 81M-GROUP 1Week 4* 0203445 100202A 100202A ND ND 82M-GROUP i 'week 4 82M-GROUP 1Week 4* 83M-GROUP 1Week 4 83M-GROUP 1Week 4* 0203446 0203446 0203447 0203447 84M-GROUP 1Week 4 0203448 84M-GROUP 1Week 4* 85M-GROUP 1Week 4 85M-GROUP 1Week 4* 0203448 0203449 0203449 86M-GROUP 4 Week 4 86M-GROUP 4 Week 4* 87M-GROUP 4 Week 4 87M-GROUP 4 Week 4* 0203450 0203450 0203451 0203451 88M-GROUP 4 Week 4 88M-GROUP 4 Week 4* 89M-GROUP 4 Week 4 89M-GROUP 4 Week 4* 90M-GROUP 4 Week 4 90M-GROUP 4 Week 4* 0203452 0203452 0203453 0203453 0203454 0203454 . 91F-GROUP 1Week 4 91F-GROUP 1Week 4* 92F-GROUP 1Week 4 92F-GROUP 1Week 4* 0203455 0203455 0203456 0203456 93F-GROUP 1Week 4 0203457 93F-GROUP 1Week 4* 94F-GROUP 1Week 4 94F-GROUP 1Week 4* 95F-GROUP 1Week 4 0203457 0203458 0203458 0203459 95F-GROUP 1Week 4* 96F-GROUP 4 Week 4 96F-GROUP 4 Week 4* 97F-GROUP 4 Week 4 0203459 0203460 0203460 0203461 97F-GROUP 4 Week 4* 98F-GROUP 4 Week 4 98F-GROUP 4 Week 4* 99F-GROUP 1Week 4 99F-GROUP 1Week 4* 100F-GROUP 1Week 4 0203461 0203462 0203462 00220033446633 0203464 100F-GROUP 1Week 4* 0203464 1\ 100202Ai u u 4 u z , n 100202A 100202A 100202A 100202A 100202A 100202A 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202AR 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A NDKI lTl Ts \ ND ND ND ND ND ND 7120 6620 3560 3630 7320 7710 8290 7830 9470 9230 ND ND ND ND ND ND ND ND 62.6 ND ND ND ND ND ND ND ND ND ND ND N* DDu=plNicoatteDIentejecctteidon(Area less than lowest calibration standard of 0.0001 pg/mL) Exygen Research Page 59 of 217 : 576 : MIN 313/023622 Exygen Study No.: 023-076 Table XXIV. Summary of POSF Residues in Rat Serum Samples Sponsor Exygen ID ID 1M-GROUP 1Day 92 1M-GROUP 1Day 92* 2M-GROUP 1Day 92 2M-GROUP 1Day 92* 3M-GROUP 1Day 92 3M-GROUP 1Day 92* 4M-GROUP 1Day 92 4M-GROUP 1Day 92* 5M-GROUP 1Day 92 5M-GROUP 1Day 92* 6M-GROUP 2 Day 92 6M-GROUP 2 Day 92* 7M-GROUP 2 Day 92 788MMM---GGGRRROOOUUUPPP222DDDaaayyy999222** 9M-GROUP 2 Day 92 9M-GROUP 2 Day 92* 10M-GROUP 2 Day 92 10M-GROUP 2 Day 92* 11M-GROUP 3 Day 92 11M-GROUP 3 Day 92* 12M-GROUP 3 Day 92 12M-GROUP 3 Day 92* 13M-GROUP 3 Day 92 13M-GROUP 3 Day 92* 1144MM--GGRROOUUPP33DDaayy9922* 0203367 0203367 0203368 0203368 0203369 0203369 0203370 0203370 0203371 0203371 0203372 0203372 0203373 0203373 00220033337744 00220033337755 0203376 0203376 0203377 0203377 0203378 0203378 U233/9 0203379 0203380 0203380 15M-GROUP 3 Day 92 15M-GROUP 3 Day 92* 1166MM--GGRROOUUPP44DDaayy9922* 0203381 0203381 00220033338822 17M-GROUP 4 Day 92 1178MM--GGRROOUUPP44DDaayy9922* 18M-GROUP 4 Day 92* 19M-GROUP 4 Day 92 19M-GROUP 4 Day 92* 20M-GROUP 4 Day 92 20M-GROUP 4 Day 92* 0203383 000222000333333888344 0203385 0203385 0203386 0203386 Set Number 100102A 100102A 100102A 0002A 100102A_ 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 100102A 111000000111000222AAA 100102A 100102A 100102A 092602B 092602B 092602B 092602B 092602B 092602B 009922660022BB 092602B 092602B 092602B 092602B 092602B 092602B 092602B 000999222666000222BBB 092602B 092602B POSF Found (ug/mL) ND ND ND Nu ND ND ND ND ND ND ND ND ND ND ND NNDD ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND NNNDDD N* DDu=plNicoatteDAetleicqtueodt (Area less than lowest calibration standard of 25 pg/mL) Exygen Research Page 60 of 217 : 577 : MIN 313/023622 Exygen Study No.: 023-076 Table XXIV (cont'). SSaummpmleasry of POSF Residues in Rat Serum Sponsor ID 21F-GROUP 1Day 92 9 1 P .fn?r> T T P 1 r> av Q 9* 22F-GROUP 1Day 92 22F-GROUP 1Day 92* 24F-GROUP 1Day 92 24F-GROUP 1Day 92* 25F-GROUP 1Day 92 25F-GROUP 1Day 92* 26F-GROUP 2 Day 92 26F-GROUP 2 Day 92* 27F-GROUP 2 Day 92 27F-GROUP 2 Day 92* 28F-GROUP 2 Day 92 28F-GROUP 2 Day 92* 29F-GROUP 2 Day 92 29F-GROUP 2 Day 92* 30F-GROUP 2 Day 92 30F-GROUP 2 Day 92* 31F-GROUP 3 Day 92 31F-GROUP 3 Day 92* 32F-GROUP 3 Day 92 32F-GROUP 3 Day 92* ^ F .n P O T T P 9 n a y 0 ? 33F-GROUP 3 Day 92* 34F-GROUP 3 Day 92 34F-GROUP 3 Day 92* 35F-GROUP 3 Day 92 35F-GROUP 3 Day 92* 36F-GROUP 4 Day 92 36F-GROUP 4 Day 92* 37F-GROUP 4 Day 92 37F-GROUP 4 Day 92* 38F-GROUP 4 Day 92 38F-GROUP 4 Day 92* 39F-GROUP 4 Day 92 39F-GROUP 4 Day 92* 40F-GROUP 4 Day 92 40F-GROUP 4 Day 92* Exygen ID 0203387 0203387 0203388 0203388 0203389 0203389 0203390 0203390 0203391 0203391 0203392 0203392 0203393 0203393 0203394 0203394 0203395 0203395 0203396 0203396 0203397 0203397 0203398 0203398 0203399 0203399 0203400 0203400 0203401 0203401 0203402 0203402 0203403 0203403 0203404 0203404 0203405 0203405 Set Number 092702A 092702A 009922770022AA092702A 092702A 092702A 092702A 092702A 092702A 092702A 092702A 092702A 092702A 092702A 092702A 092702A 092702A 092702A 092702A 100202A 100202A 10(1909 A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A 100202A , POSF Found (pg/mL) NNDD NNDD ND ND ND ND ND ND ND ND ND ND ND ND NNDD ND ND ND NNDD NNNDDD ND ND ND ND ND ND ND ND ND ND ND ND N* DDu=plNicoatteDAetleiqctueodt(Area less than lowest calibration standard of 25 jig/mL) Exygen Research Page 61 of 217 : 578 : MIN 313/023622 Exygen Study No.: 023-076 Table XXIV (cont'). Summary of POSF Residues in Rat Serum Samples Sponsor Exygen ID ID 41M-GROUP 1Day 121 42M-GROUP 1Day 121 0203406 0203407 4423MM--GGRROOUUPP11DDaayy112211* 43M-GROUP 1Day 121* 44M-GROUP 1Day 121 44M-GROUP 1Day 121* 45M-GROUP 1Day 121 45M-GROUP 1Day 121* 46M-GROUP 2 Day 121 46M-GROUP 2 Day 121* 47M-GROUP 2 Day 121 47M-GROUP 2 Day 121* 48M-GROUP 2 Day 121 48M-GROUP 2 Day 121* 49M-GROUP 2 Day 121 49M-GROUP 2 Day 121* 50M-GROUP 2 Day 121 50M-GROUP 2 Day 121* 51M-GROUP 3 Day 121 5512MM--GGRROOUUPP33DDaayy112211* 52M-GROUP 3 Day 121* 53M-GROUP 3 Day 121 53M-GROUP 3 Day 121* 54M-GROUP 3 Day 121 54M-GROUP 3 Day 121* 55M-GROUP 3 Day 121 55M-GROUP 3 Day 121* 56M-GROUP 4 Day 121 56M-GROUP 4 Day 121* 57M-GROUP 4 Day 121 57M-GROUP 4 Day 121* 58M-GROUP 4 Day 121 58M-GROUP 4 Day 121* 59M-GROUP 4 Day 121 59M-GROUP 4 Day 121* 6600MM--GGRRQOUUPP44DDaayy112211* 00220033440078 0203408 0203409 0203409 0203410 0203410 0203411 0203411 0203412 0203412 0203413 0203413 0203414 0203414 0203415 0203415 00220033441166 0203417 0203417 0203418 0203418 0203419 0203419 0203420 0203420 0203421 0203421 00220033442222 0203423 0203423 0203424 0203424 00220033442255 Set Number 100302A 100302A 100302A 100302A 100302A 100302A 100302A 100302A 100302A 100302A 100302A 110000330022AA 100302A 100302A 100302A 100302A 100302A 110000340022AA 110000440022AA 100402A 100402A 110000440022AA 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 111000000444000222AAA POSF Found (pg/mL) ND ND ND ND ND ND ND ND ND ND ND NNDD ND ND ND ND NNDD NNDD NNDD NNDD ND ND ND ND ND ND ND NNDD ND ND ND NNDD N* DDu=plNicoatteDAetleicqtueodt (Area less than lowest calibration standard of 25 pg/mL) Exygen Research Page 62 of 217 : 579 : MIN 313/023622 Exygen Study No.: 023-076 Table XXIV (cont'). SSaummpmleasry of POSF Residues in Rat Serum Sponsor Exygen ID ID 61F-GROUP 1Day 121 0203426 61F-GROUP 1Day 121* 0 7 0 3 4 2 6 62F-GROUP 1Day 121 0203427 62F-GROUP 1Day 121* 0203427 64F-GROUP 1Day 121 0203428 64F-GROUP 1Day 121* 0203428 65F-GROUP 1Day 121 0203429 65F-GROUP 1Day 121* 0203429 66F-GROUP 2 Day 121 0203430 66F-GROUP 2 Day 121* 0203430 67F-GROUP 2 Day 121 0203431 67F-GROUP 2 Day 121* 0203431 68F-GROUP 2 Day 121 0203432 68F-GROUP 2 Day 121* 0203432 69F-GROUP 2 Day 121 0203433 69F-GROUP 2 Day 121* 70F-GROUP 2 Day 121 0203433 0203434 70F-GROUP 2 Day 121* 0203434 71F-GROUP 3 Day 121 0203435 71F-GROUP 3 Day 121* 0203435 72F-GROUP 3 Day 121 0203436 72F-GROUP 3 Day 121* 0203436 7 ^ F -r.R n T T P 7 D a v 171 0203437 73F-GROUP 3 Day 121* 0203437 74F-GROUP 3 Day 121 0203438 75F-GROUP 3 Day 121 0203439 75F-GROUP 3 Day 121* 0203439 76F-GROUP 4 Day 121 0203440 76F-GROUP 4 Day 121* 0203440 77F-GROUP 4 Day 121 0203441 77F-GROUP 4 Day 121* 0203441 78F-GROUP 4 Day 121 0203442 78F-GROUP 4 Day 121* 0203442 79F-GROUP 4 Day 121 0203443 79F-GROUP 4 Day 121* 0203443 80F-GROUP 4 Day 121 0203444 80F-GROUP 4 Day 121* 0203444 * Duplicate Aliquot Set Number 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100402A 100702A 100702A 100702A 100702A 100702A 100702A 100702A 100702A 100702A 100702A 100702A 100702A 100702A 110000770022AA 100702A 100702A , POSF Found (ug/mL) ND ND ND ND ND ND ND ND ND ND ND ND ND ND NNDD ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND NNDD NNDD ND ND Exygen Research Page 63 of 217 : 580 : MIN 313/023622 Exygen Study No.: 023-076 Table XXIV (coni'). SSaummpmleasry of POSF Residues in Rat Serum Sponsor Exygen ID ID 81M-GROUP 1Week 4 82M-GROUP 1Week 4 0203445 0203446 8823MM--GGRROOUUPP11WWeeeekk44* 0203446 0203447 84M-GROUP 1Week 4 84M-GROUP 1Week 4* 85M-GROUP 1Week 4 85M-GROUP 1Week 4* 86M-GROUP 4 Week 4 86M-GROUP 4 Week 4* 87M-GROUP 4 Week 4 87M-GROUP 4 Week 4* 88M-GROUP 4 Week 4 88M-GROUP 4 Week 4* 89M-GROUP 4 Week 4 90M-GROUP 4 Week 4 90M-GROUP 4 Week 4* 91F-GROUP 1Week 4 91F-GROUP 1Week 4* 9922FF--GGRROOUUPP11WWeeeekk44* 0203448 0203448 0203449 0203449 0203450 0203450 0203451 0203451 0203452 0203452 0203453 0203454 0203454 0203455 0203455 0203456 0203456 93F-GROUP 1Week 4 93F-GROUP 1Week 4* 94F-GROUP 1Week 4 94F-GROUP 1Week 4* 95F-GROUP 1Week 4 95F-GROUP 1Week 4* 96F-GROUP 4 Week 4 96F-GROUP 4 Week 4* 97F-GROUP 4 Week 4 97F-GROUP 4 Week 4* 98F-GROUP 4 Week 4 9989FF--GGRROOUUPP41WWeeeekk44* 99F-GROUP 1Week 4* 1OOF-GROUP 1Week 4 0203457 0203457 0203458 0203458 0203459 0203459 0203460 0203460 0203461 0203461 0203462 0203462 0203463 0203463 0203464 100F-GROUP 1Week 4* 0203464 Set Number 101702A 101702A 101702A 101702A 101702A 101702A 101702A 101702A 101702A 101702A 101702A 101702A 101702A 101702A 101702A 101702A 101702A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A 100802A POSF Found (ng/mL) ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND * Duplicate Aliquot ND = Not Detected (Area less than lowest calibration standard of 25 pg/mL) Exygen Research Page 64 of 217 : 581 : MIN 313/023622 Exygen Study No.: 023-076 Table XXV. Summary of PFOS Residues in Rat Urine Samples Sponsor Exygen Set ID ID Number 1 1* 2 0203563 0203563 0203564 100302A 100302A 100302A 2* 3 3* 44* 0203565 0203565 0203566 0203566 100302A1AnW mJ Wn iof i Xa 100302A' 100302A 100302A 5 5* 6 6* 7 7* 8 8* 99* 0203567 0203567 0203568 0203568 0203569 0203569 0203570 0203570 0203571 0203571 100302A 100302A 100302A 100302A 100302A 100302A 100302A 100302A 100302A 100302A NN* DDQu==plNNicooattteD11Q1111111121111110111212314I56107e8203u9456*7*8n*09*****t***ajeneccttitefidioanb(Alere(Raelessps0000000o0000000000000002222222nt222222222222222h00000000s00000000000000a33e333333333333333333n335555555555555>55555555577777l7777777777788888o8223t345456767889911h00w22aenstthcealaibrer11111111111111a1111a111100000000000000t00000000o00000i00000000000000o00033f33333333333333333n33300000t000000000000000h002222222s2222222222222e22AAAtAAAAAAAAAAAAAAAaAAAAlRRRnRRRRRoRRRRRRRRRRdwaersdt PFOS Found (ng/mL) - ND nd ND ND ND ND ND NQ ND NQ 129 123 151 150 113 104 187 197 168 169 357 313 400 411 190 260 130 133 488 592 3870 3330 1790 1490 894 1000 1060 1070 925 929 ocfal0i.b0r0a0ti1onpgst/amnLd)ard but less than the LOQ. Exygen Research Page 65 of 217 : 582 : MIN 313/023622 Exygen Study No.: 023-076 Table XXV (cont')* Summary of PFOS Residues in Rat Urine Samples Sponsor Exygen Set PFOS _________ ID__________ ID Number Found (ng/mL) NN*DDQu==plNNicooattt22222e22222D23Q2323223332232343123333334356733381933402312453I4567869780e1*90u*2*3*4*5**67n*8*9*0******t****ajeneccttitefidioanb(Alere(Raelessp000000000s00000000000o000n00000000000020002022222222222222222t22n22o2222222222220222002h0000000000000000000s0m0000000000000300330333a33333333e3333333333333333333335335n35355555s55555555555555555>55555555668c6686868888888888899999l999999999999M990030300o4055467678t81991002332545677688h9911002w2aenstthcealairber111111111111a111111111a11111111111111111110000000000000t000000000000000000000o000000i00000000000000000000000o00000000000000f00077777777777777777777777n77777777777777777t000000000000000000000000h0000000000000000s222222222222222222222222222e222222222222t2AAAAAAAAAAAAAAAAAAAAaAAAAAAAAAAAAAAAAAAAAlnoRRRRRRRRRRRR-dwaerdstocfal0i.b0r0a0ti1onpgsN4NN5NNtN/NN3322NN241411171613415541a411m2219360940451D7249D17D8Dn7DD93587QQQ153265Q3.......L.84104711492d0471802758747122588000000)a0000rd but less than the LOQ. Exygen Research Page 66 of 217 : 583 : MIN 313/023622 Exygen Study No.: 023-076 Table XXV (coni'). Summary of PFOS Residues in Rat Urine Samples Sponsor Exygen Set PFOS _________ ID___________ ID Number Found (ng/mL) NN*DDQu==plNNicooattt444444e4444D4545Q4545454554545512556355455567515859526031245364I75687918*0e*90u*23**45**67*8*9n*0*******t***aejneccttitefidioanb(Alere(Raelessp00000000000s00000000o0000n00000000000220000220222222222222222tn222?2222222222022022220002h0000000000000r0000s0000000000300030000333v3a3333333e333333333333333333363336333n*666366666666666666666666>6666666066606f66000600000000011111l1111i1111111131221322524o425i6776889911t00232354546776889119h020w2aenstthcealaibrer111111111111a11111111a11111111111111111111000000000000t00000000000000000000o0000000i000000000000000000000000o00000000000010f111777777777777777777777777n7777777777774444t0000000000000000000000000h00000000000000022s22222222222222222222222222e22222222222t2BBBBBBBBBBBBBBBBBBaBBBBBBBBBBBBBBBBBBBBBBlnoRRRRRRRRRR-dwaerdstocfal0i.b0r0a0ti1onpgsN4N3tNN3NN3554/N4NN7N6911a2241m121132918968875551850274DDD1nDD2DDD54D2D3025502499.58.....32.....L672d08877515973022283958505130600)a00rd but less than the LOQ. Exygen Research Page 67 of 217 : 584 : MIN 313/023622 Exygen Study No.: 023-076 Table XXV (cont'). Summary of PFOS Residues in Rat Urine Samples Sponsor ID Exygen ID Set Number PFOS Found (ng/mL) NN*DDQu==plNNicooattt6666e666D6Q767667677676766777778177274775767789710812345I456678789e190u02*32**54*7*68**n*9*0******t***ajeneccttitefidioanb(Alere(Raelessp0000000s0000000000o0000000000000000000002222222222222222t2n22222222222222222222200h000000000000000s00000000000000000000033a33333333e33333333333333333333333333n336666666666666666666666>6666666666666666222222222222232l3333333333333333334434o343545476t7688919100233245547766h898119w00aenstthcealaibrer1111a111111a11111111111111111111111111001010t000000000000000000o0000000i00000002202022222222o22222222222222222f222222221211211111111111n11111111111111111t111110010100000000000000h000000000000000000s022020222222222222222e22222222222t2222222BB22BBBBBBBBBBBBaBBBBBBBBBBBBBBBBBBBBBlBBBnoRRRRdw.aersdtocfal0i.b0r0a0ti1onpgs7NN63tN36/NN65NN44N11221a3m1315411162616278253623776DD5n2D45DDD1D5D22723276.33774....7....L.1811555d939718028-385232685006440)0ard but less than the LOQ. Exygen Research Page 68 of 217 : 585 : MIN 313/023622 Exygen Study No.: 023-076 Table XXVI. Summary of PFOA Residues in Rat Urine Samples Sponsor Exygen Set PFOA _________ ID___________ ID Number Found (ng/mL) NN*DDQu==plNNicooattteDQ2431151671191812211413115116171918121*1**01*1I1*2**34*5*6u0e781902345n7680*9******t**a**jeneccttitefiidoanb(Alere(Raelessp0000000000s000000000o0000000000000000200200202222222222222222n22t2222222222222220202022000h0000000000000s0000000000000000030300303a333333e33333333333333333333333335335n353355555555555555555555>555555555555655656556666666667667777l777777777777778873388o488554766788t199100223345546677889h11900w22aenstthcealaibre11r11111111111111111111111111a1111111111a1100000000000000000000000000000000t00000000o00000000i000000000000000000000000000000o0033f3333333333333333333333333333333333333n300000000t00000000000000000000000000000000h222222222s222222222222222222222222222222e2AAAtAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAaAAAAAAAlRRRRnRRRRRRRRoRRRRRRRRRRRRRRRR.dwaersdtocfal0i.b0r0a0ti1onpgsNN11NNtN/NN2N3322554242122222355225577a447n744078331439440Q83276Q2623Q3Dn68Q885QQ1Q6i2..37379L848032008600334894d71421630800000)00a000rd but less than the LOQ Exygen Research Page 69 of 217 : 586 : MIN 313/023622 Exygen Study No.: 023-076 Table XXVI (cont'). Summary of PFOA Residues in Rat Urine Samples Sponsor Exygen Set PFOA ID __________ ID__________ Number ______Found (ng/mL) NN*DDQu==plNNicooattt2222222e22222D3Q2322332323213332334343335336178339233403145236I748596*71*08e0*u92*3*45***67*8n*90*******t***ajeneccttitefidioanb(Alere(Raelessp0000000000000s00000000o00000000000220020002220002222222222222222n2t222222222002202202002220h000000000000000s000000000003300030330300a33333333e333333333333333333553333535n5533355555555555555555555>55555588565668888666888888889999999l9999999999933909050454000o6776889911t00322354547667889h19100w22aenstthcealairbe11r1111111111111111111111111a111111111a1111000000000000000000000000000t000000000000000o0000i000000000000000000000000000000o0000777f777777777777777777777777777777777n777700000t000000000000000000000000000000000h0022222222222s222222222222222222222222222e22AAtAAAAAAAAAAAAAAAAAAAAAAAAAAaAAAAAAAAAAAlRRRnRRRRRRoRRRRRRRRRRRRRRRd.waerdstocfal0i.b0r0a0ti1o' npgs11N2N2NN21N1211tN12111/344113712211811111a13m24447780585500915523798697Q0Q3892DD6nQQ6.,.25191.6134559848304247L6119920608746d00000000000000000000)a00000000rd but less than the LOQ Exygen Research Page 70 of 217 : 587 : MIN 313/023622 Exygen Study No.: 023-076 Table XXVI (cont'). Summary of PFOA Residues in Rat Urine Samples Sponsor Exygen Set PFOA _________ ID______________ ID Number Found (ng/mL) NN*DDQu==plNNicooattt4444444e44445D4Q455445454545555125556354555657185592053651423674I58697*810*e92*0u3**54*6*7*8*9n*0********t**ajeneccttitefidioanb(Alere(Ra elessp0000000000000s000000000o0000000000022000022022002222222222222222tn222222222220022202002220h0000000000000000s000000000003300003303003a33333333e33333333333333333336633336663n63366666666666666666666>66666660066660006066000000001111l11111111111111133212524425o2276678899t1100223355446776889h1910w022aenstthcealairber111111111111a11111a111111111111111Q011001110100100100000t000000000U000o00000i000000000Q0000000000000000o00000000000f11007070070770070777777777777n77777777777744t7007707070077Q07000000000000h00000U0000000220020s202200202222222222222e22222222222t2B2B22B2B2BB22B2BBBBBBBBBBBaBBBBBBBBBBBBBBBBBlBBBBBnoRR'dwaersdt - ND ND ND ND ND ND ND ND ND ND 80.0 76.1 43.7 44.1 45.1 48.7 40.3 40.0 49.9 49.8 73.4 69.8 80.1 83.5 154 157 53.7 54.6 1660 1740 241 203 143 138 167 171 115 116 192 189 ocfal0i.b0r0a0ti1onpgst/amnLd)ard but less than the LOQ Exygen Research Page 71 of 217 : 588 : MIN 313/023622 Exygen Study No.: 023-076 Table XXVI (cont'). Summary of PFOA Residues in Rat Urine Samples Sponsor Exygen Set PFOA _________ ED___________ ID Number Found (ng/mL) 61 61* 62 62* 64 64* 65 65* 66 66* 67 67* 68 68* 69 69* 70 70* 71 71* 72 0203623 0203623 0203624 0203624 0203625 0203625 0203626 0203626 0203627 0203627 0203628 0203628 0203629 0203629 0203630 0203630 0203631 0203631 0203632 0203632 0203633 102102B 102102B 102102B 102102B 102102B . 102102B 102102B 102102B 102102B 102102B 102102B 102102B 102102B 102102B 102102B 102102B 102102B 102102B 102102B 102102B 102102B ' ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND 72 73 73* 74 74* 75 75* 76 76* 0203633 0203634 0203634 0203635 0203635 0203636 0203636 0203637 0203637 102102B 102102B 102102B 102102B 102102B 102102B 102102B 102102B 102102B ND ND 23.3 ND ND NQ NQ 19.6 20.8 NN*DQD==upNNlioocatttDQe777877787e89u0I7890t****naenjcettcieftdiiaob(nAlere(Raelesspso00000000tn2222222h2s0000000a0e33n333333>66666666l334433o44th8811w9900aenstthcealaibreraa11111111toi00000000of22222222nt11111111h00s000000et22222222alBBBBBBBBnodwaersdtocfal0i.b0r0a0ti1onpgst/a2m2NN11NNn3321LDDDdD....3459)ard but less than the LOQ Exygen Research Page 72 of 217 589 : MIN 313/023622 Exygen Study No.: 023-076 Table XXVII. Summary of POSF Residues in Rat Urine Samples Sponsor ID 1 1* 2 3 34* 5 5* 6 6* 7 88* 99* 10 11 11* 12 12* 13 13* 14 14* 15 15* 16 1178 1189* 19* 2210 2232 24 24* 25 25* Exygen ID 0203563 0203563 0203564 0203565 0203565 0203566 0203567 0203567 0203568 0203568 0203569 0203570 0203570 0203571 0203571 0203572 0203573 0203573 0203574 0203574 0203575 0203575 0203576 0203576 0203577 0203577 0203578 0203579 0203580 0203580 0203581 0203581 0203582 0203583 0203584 00220033558856 0203586 00220033558877 Set Number 101002A 101002A 101002A 101002A 101002A. 101002A 101002A 101002A 101002A 101002A 101002A 101002A 101002A 101002A 101002A 101002A 101102A 101102A 101102A 101102A 101102A 101102A 101102A 101102A 101102A 101102A 101102A 101102A 101102A 101102A 101102A 101102A 101102A 101402A 101402A 101402A 101402A 101402A 110011440022AA POSF Found (ug/mL) ' ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND NNDD ND ND ND NNDD ND NNDD ND NNDD ND ND ND ND ND ND ND ND ND ND ND ND N* DDu=plNicoatteDAetleicqtueodt (Area less than lowest calibration standard of 25 pg/mL) Exygen Research Page 73 of 217 : 590 : MIN 313/023622 Exygen Study No.: 023-076 Table XXVII (cont'). Summary of POSF Residues in Rat Urine Samples Sponsor Exygen Set POSF ID ID _____ Number_________ Found (pg/mL) 26 27 28 28* 29 30 30* 31 32 33 34 3356 3378 39 4410 4422* 43 4434* 44* 4456 46* 47 47* 48 48* 49 49* 50 50* 51 51* 5522* 53 53* 0203588 0203589 0203590 0203590 00220033559912 0203592 0203593 0203594 0203595 0203596 0203597 0203598 00220033569090 00220033660012 0203603 00220033660044 0203605 0203605 00220033660066 00220033660078 0203608 00220033660099 0203610 0203610 0203611 0203611 0203612 0203612 0203613 0203613 0203614 0203614 00220033661155 101402A 101402A 101402A 110011440022AA 101402A 101402A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 102202A 101502A 101502A 110011550022AA 101502A 110011550022AA 110011550022AA 110011550022AA 101502A 110011550022AA 101502A 101502A 101502A 101502A 102902A 102902A 102902A 102902A 110022990022AA ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND NNDD NNDD ND NNDD ND ND ND ND ND ND ND N*DD=upNlioctatDeeAtelciqteudot(Area less than lowest calibration standard of 25 |ig/mL) Exygen Research Page 74 of 217 : 591 : MIN 313/023622 Exygen Study No.: 023-076 Table XXVII (cont'). SSuammmplaersy of POSF Residues in Rat Urine Sponsor Exygen Set POSF _________ ID___________ ID Number Found (ng/mL) 54 54* 55 5556* 56* 5577* 58 58* 59 59* 60 60* 61 6612* 62* 64 64* 65 65* 6666* 6677* 68 68* 69 69* 70 70* 7712 72* 73 74 74* 0203616 0203616 0203617 00220033661178 0203618 00220033661199 0203620 0203620 0203621 0203621 0203622 0203622 0203623 00220033662234 00220033662254 0203625 0203626 0203626 0203627 0203627 0203628 00220033662289 0203629 0203630 0203630 0203631 00220033663312 0203633 00220033663334 0203635 0203635 102902A 102902A 102902A 110022990022AA . 110022990022AA 102902A 102902A 102902A 102902A 102902A 102902A 102902A 102902A 102902A 102902A 110012690022AA 101602A 101602A 101602A 101602A 101602A 101602A 111000111666000222AAA 101602A 101602A 101602A 101602A 101602A 101602A 110011660022AA 102102A 102102A ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND NNDD ND ND ND ND ND ND NNDD ND ND ND ND ND ND ND ND ND ND * Duplicate Aliquot ND = Not Detected (Area less than lowest calibration standard of 25 |ig/mL) Exygen Research Page 75 of 217 : 592 : MIN 313/023622 Exygen Study No.: 023-076 Table XXVII (cont'). SSaummpmleasry of POSF Residues in Rat Urine Sponsor ID 75 75* 76 - 77 77* 78 7789* 79* 80 80* Exygen ID 0203636 0203636 00220033663378 0203638 0203639 0203639 00220033664400 0203641 0203641 Set Number 102102A 102102A 102102A 110022110022AA ' 102102A 102102A 102102A 102102A 102102A 102102A , POSF Found (ug/mL) ND ND ND ND ND ND ND ND ND ND ND N* DDu=plNicoatteDAetleiqctueodt(Area less than lowest calibration standard of 25 |ig/mL) Exygen Research : 593 : Page 76 of 217 MIN 313/023622 Exygen Study No.: 023-076 FIGURES Exygen Research : 594 : Page 77 of 217 MIN 313/023622 Exygen Study No.: 023-076 Figure 1. Typical Calibration Curve for PFOS I 100102A.rdb ( P F O S ): "Linear" R e g re ss io n ("1 / x" weighting): y = 1084.56 x + 7 5 .115 (r = 0.9978965) 5545 5400 5200 5000 4800 4600 4400 4200 4000 3800 3600 3400 3200 3000 2800 2600 2400 2200- 2000 1800 1600 1400 1200 1000 800 600 400 200 Concentration, ng/mL Exygen Research Page 78 of 217 : 595 : MIN 313/023622 Exygen Study No.: 023-076 Figure 2. Typical Calibration Curve for PFOA 1 10010 2A.rdb (P F O A ) : "Linear" R e g re ss io n ("1 / x" weighting): y = 18602.7 x + 39 0 .5 0 9 (r = 0.9972473) 9 .0 e 4 8.5e4 8 .0 e 4 7 .5 e 4 7 .0 e 4 6 .5 e 4 6.0e4 5 .5 e 4 5.0e4 4 .5 e 4 4.0e4 3 .5 e 4 3 .0 e 4 2.5e4 2 .0 e 4 1.5e4 1.0e4 5000.0 Concentration, ng/mL Exygen Research Page 79 of 217 : 596 : MIN 313/023622 Exygen Study No.: 023-076 Figure 3. Typical Calibration Curve for POSF File L :\023-076\RAWDATA\101102A\H0110205.D operator Acqui red 11 OCt 2002 9:53 am using AcqMethod PAL502 Sample Name: POSF Std. 5pL of 500ug/m l , Imu headspace Mise info : C10102-5, Study#023-076 vial Number CurrentMeth: L:\023-076\RAWDATA\101002A\POSF.M Compound: Ret Time concentration : Pk # and Tvoe: POSF 3.52 493.33 \iq/tnl RTHINT used 3.00 4 0 0 Target Signal Ratios 69.00 131.00 219.00 0.00 100.OX 0.041.5 20.1 Limits 0.0- 0.016.1- 64.3 8.0- 31.8 Lim its 3.52 3.52 3.52 3.52 3.42 to 3.60 3.00 41 Merged Resp integ Type 969878 0402983 195175 sys def sys def sys def sys def Response 1.00e+006- POSF 8.OOe+O05 6.00e+005- 4.00e+005- 2.0Qe+00S 100 200 300 400 Amount Response 1.97e+003 * Amt - 1.70e+003 Coef o f oet (rA2) - 0.997 Curve Fit: wlrCl/a) HO110205.D Thu Oct 17 15:28:17 2002 500 Page 2 Exygen Research 597 : Page 80 of 217 MIN 313/023622 Exygen Study No.: 023-076 Figure 4. Chromatogram Representing a 0.1 ng/mL standard for PFOS and PFOA S s 3 2 H k w : 2: 52 iKSS 52.. 52. Exygen Research : 598 : Page 81 of 217 MIN 313/023622 : 599 : MIN 313/023622 Exygen Study No.: 023-076 Figure 6. PCFhOroSmaantdogPrFamOARe(EprxeysgeenntiInDg 0a2C01o6n8tr4oCl RonattrLolivAe,rSSeatm: ple for 100802B) SampleName: `1006028-208* SampleID:`CW ICPVeoapmikieemNeTIannmty:dep*:ee0x*.2P.0F1O86S4U`CnkoMnn5toarweoeln(Ae*e): A*nn.o(ta9te.0e"mu* lc u iccqq.. lTDe iatnetaed.. Conei 1010/.1*0J.0/.000202 n/mL PM SampleName: ' 100602S-208- SempleID: *CI PeakName: *PFOA* Mee^ee): `413.0069.0i waCm^opmlleemeTInnytpd*ee0xi2.01864UCnko4nn3torwolnA* Annotato*' 'eqlccq..u DTleiatmeteed.. Cone. 1001/.14091.0/.000220 nq/aL PM Exygen Research Z T T 7 6 3.5183 : 600 : Page 83 of 217 MIN 313/023622 : 601 : MIN 313/023622 Exygen Study No.: 023-076 Figure 8. fCohrrPoFmOaStoagnradmPFROepAr,e(sEenxtyignegnaIDC:on02tr0o1l6R82atCSoenrutrmolSAa,mSpetl:e 092502A) 090/2.097/037 ng/mL sWtHaadidigtUhhiTt ii Sampta Nam 082602B-206* Sampta lOr 'Ctrt" FUa: "rat aanjm.wiH 09/29/02 Exygen Research 4.7136 : 602 : Page 85 of 217 MIN 313/023622 : 603 : MIN 313/023622 Exygen Study No.: 023-076 Figure 10. fCohrrPoFmOaStoagnradmPFROepAr,e(sEenxtyignegnaIDC:on02tr0o1l6R83atCUornintreoSl aAm, Spelet: 100302A) 10/04/02 0.7070 Sap. Widthi Exygen Research : 604 : Page 87 of 217 MIN 313/023622 : 605 : MIN 313/023622 : 606 : MIN 313/023622 : 607 : MIN 313/023622 Exygen Study No.: 023-076 Figure 14. Chromatogram Representing Control Rat Serum fortified with 10 ng/mL of PFOS and PFOA (Exygen ID: 0201682 SpkA, Set: 0100202A) SamptaMain: '100202A-110' 3ampteID:"Spfc* F U : PoafcN a im : "PFOS" U*m(m): '49S.(VM.Omu* --Conw-iwnt-*"02018828pkioA10nj^niL' Annotation:** QC 0.250 llCUlatad 0.253 10/03/02 Exygen Research : 608 : Page 91 of 217 MIN 313/023622 : 609 : MIN 313/023622 Exygen Study No.: 023-076 Figure 16. wCihtrho1m0antogg/mraLmoRf PepFrOesSenantidngPFCOonAtr(oElxRyagtenUrIDin:e0f2o0r1ti6fi8e3d SpkA, Set: 100302A) 8.7537 Modi(ladt SampleNamM00302A-110* SampleID;'Spk' Fil"ralurina.wtff 2.7440 cted KTt Widthi Haight M i. U 7.8615^8.0972 Exygen Research : 610 : Page 93 of 217 MIN 313/023622 : 611 : MIN 313/023622 Exygen Study No.: 023-076 Figure 18. Chromatogram Representing Rat Liver Sample for PFOS and PFOA (Exygen ID: 0203553, Sponsor ID: 91 Set 102102A) XBoudnicfhliandgiF 1 02/2.949/042 ng/L SuroNam'1021dati39' SairobID:`Sampia* Ria: 'ratttvw.wW ' Annotation:1 Unk*no/wAn 100/2.410/022 AVdajl.. UUnnttiiee Exygen Research : 612 : Page 95 of 217 MIN 313/023622 : 613 : MIN 313/023622 MIN 313/023622 : 615 : MIN 313/023622 MIN 313/023622 : 617 : MIN 313/023622 Exygen Study No.: 023-076 APPENDIX A A(EmxeyngdeSmntueSMdntuytIsadNPnya/rdn3Nod1to3oD.c0eo2vl 3ia-0ti7o6n)s Exygen Research : 618 : Page 101 of 217 Study Number : MEN/313 CONHDENTIAL MIN 313/023622 Exygen Study No.: 023-076 T-lU U H H u n tin g d o n ' Life Sciences PROTOCOL PERFLUOROOCTANESULFONYL FLUORIDE (POSF; T-766L4) TOXICITY STUDY BY INHALATION ADMINISTRATION TO CD RATS FOR 13 WEEKS FOLLOWED BY A 4-WEEK RECOVERY PERIOD S33BMMtuPilaCCduioelnnrgpteo2rr2a0t-e2TEo-0x2icology MUSNA55133-3220 Research Laboratory WHuonotlilnegydRonoaLdife Sciences Ltd AHlucnotninbgudryon PCEam28b4riHdgSeshire ENGLAND Exygen Research : 619 : Page 102 of 217 MIN 313/023622 : 620 : MIN 313/023622 Exygen Study No.: 023-076 Study Number : M1N/313 H u n tin g d o n Life Sciences PROTOCOL APPROVAL PERFLUOROOCTANESULFONYL FLUORIDE (POSF; T-7661.4) TOXICITY STUDY BY INHALATION ADMINISTRATION TO CD RATS FOR 13 WEEKS FOLLOWED BY A 4-WEEK RECOVERY PERIOD T.J. Kenny, B.Sc (Hons.). Study Director, Huntingdon Life Sciences Ltd. ..XiaOESjuleieC Date AThney scihgannagture formal am of the Study Director confirms e subsequent to the date of this protocol as the working document for the study. the Study Director's signature will be documented DM.aWna. gCeomoemnbt,s, B.Sc., M.Sc. Huntingdon Life Sciences Ltd, Date John Butenhoff Sponsor, Date P lease sig n both co pies o f this page, retain one fo r yo u r records a n d return one to the S tu d y D irecto r a t H untingdon L ife Sciences. Final Protocol Exygen Research Page 104 of 217 : 621 : MIN 313/023622 Exygen Study No.: 023-076 Study Number : MIN/313 H u n tin g d o n * Life Sciences ijl, ijluukuu (ro s y ; T-7661.4) TOXICITY STUDY BY INHALATION ADMINISTRATION TO CD RATS FOR 13 WEEKS FOLLOWED BY A 4-WEEK RECOVERY PERIOD Enquiry Number: 23923B Number of pages for internal distribution: 22 Tais working document is approved for circulation and use: ^Dale 2CO>* Primary location of study HCHauumnnttbiinnriggdddgooennshRireesearch Centre PE284HS Building Number Y14 All procedures to be performed at the above site unless otherwise detailed below. Location of specific tasks Blood chemistry Histology Ssuebrasmtan, cuerianned, lmiveetrafboorlitteesst Routinely done at Huntingdon Research Centre, Huntingdon, CCeanmtrber,idEgyees,hSiruef,fPolEk2,8IP42H3S7,PbXutfmoralyobgiesptiecraflorremaseodnast. Eye Research Routinely done at Huntingdon Research Centre, Huntingdon, CCeanmtrber,idEgyees,hSiruef,fPolEk2,8IP42H3S7,PbXutfmoralyobgeisptiecraflorremaseodnast. Eye Research Sponsor. Exygen Research : 622 : Page 105 of 217 MIN 313/023622 : 623 : MIN 313/023622 : 624 : MIN 313/023622 : 625 : MIN 313/023622 Exygen Study No.: 023-076 Study Number : MIN/313 - H u n tin g d o n Life Sciences 12. Scheduled time plan Animals to arrive Treatment to commence Terminal sacrifice to commence Histopathology to be completed Draft report to be issued 13. Identity of treatment groups (to be selected from 118 animals ordered) _ December 2001 December 2001 March 2002 June 2002 July 2002 (estimated) (estimated) Group 1 2 3 i4 Treatment Control Test substance Test substance Test substance Expo(psuprme)level 0 30 100 300 -MaMleaiinsFteumdyale 55 55 55 55 NMRuaemlceobveerroyFfpeamhnaiamsleeata 55 55 55 55 SatelliteFsttnumdylf 55 00 00 55 Mi instudy Group Cage numbers Animal numbers Male Female Male Female 1 1 5 1-5 21-25 2 2 6 6-10 26-30 33 7 11-15 31-35 4. 4 8 16-20 36-40 Recovery phase Cage numbers Animal numbers Male Female Male Female 9 13 4 A 5 61-65 10 14 46-50 66-70 11 15 51-55 71-75 12 16 56-60 76-80 Exygen Research Finft Prnfrwnl Page 109 of 217 : 626 : MIN 313/023622 Exygen Study No.: 023-076 Study Number !MIN/313 H u n tin g d o n Life Sciences Female 96-100 TEST SUBSTANCE ANDATMOSPHERE GENERATION Inorderfor Huntmjdon Life Sciences to comply with the Health and Safety at Work etc. Act 1974 athneds*tuedyCothnatrtothl eofSSpuobnsstoarnscheaslHl parzoavriddoeuHs tuontHinegadltohnRLeigfeulSatciioennsce1s99^9t,hit^is a^ cronZditoionVofiUvnd^ertTaki^ng breygatrhdeinSgpkonnosworn toor pHoutenntitniagldhoanzaLridfse aSsscoiecniacteesd. wTithhethSephoannsdolrindgualnldaulsseoo0f a0ny^ s1ub^st7ance suSpplied !bSeuchhanfod. lremd,a.ibntyiot-hne,ilnabtho,Mer_aaftonorarmyg.eomAfeant tcthSoemerdrpviliseccteersed--ta-iHt-o-Hn-u-n-uo-tn-if-nt-iSogna-dg-fo-de-no-t--ynLLMifiefaenSacSgiceeinemcneecnsetsteSbseetrafsvuouiLrcybeaesutstnhaiaenttceteeHasdutaanisatutaibsnsnsghtedaeeonetnctmemLucuisafstnet Isnaffeotnynparteiocnaurteicoenisvetadkwenililnbtehueswedortkopsleatceth. e Huntingdon Life Sciences Hazard Class, which determines Huntingdon Life Sciences Hazard Class Filial Protocol Exygen Research : 627 : Page 110 of 217 MIN 313/023622 : 628 : MIN 313/023622 : 629 : MIN 313/023622 : 630 : MIN 313/023622 : 631 : MIN 313/023622 : 632 : MIN 313/023622 : 633 : MIN 313/023622 Exygen Study No.: 023-076 Study Number : MIN/313 H u n tin g d o n Life Sciences 6.3, Bodywelght Bodyweight recording Week-1 BDaacyhthwaetetkr.eatment commences At necropsy. displaying ill-health. These data will be retainaeidditnhethme oarncihtoivriensg of Ire condition o f animals 6A Food consumption Food consumption recording Food supplied Food spilled Food remaining Haematology, peripheral Mood WWeeeekkly-1. . At intervals each week. Recorded at cage cleaning. Recorded at end of study week. 14 (Day 91) Conditions Anaesthetic Sample site Andcoagulant/Sample volume Animals Main group animals Recovery group animals gF(neoonltleodrwaelcinaengdaeoenvstetsh)r.nesiSgiaha.mt dpelpesrivcoatliloecnteodf fuonodderanlidghwtater Isoflurane Retro-orbital sinus. EDTA/0.5 ml. Citrate/0.5 mL All samples will be examined for the following c h a ra rt ^ ,... 1) Using EDTA as anticoagulant -- Haematocrit TERHoreaytteaitcmhlurlooleogucclycoyotbetceinycsotceuocnnotcuennttration Differential leucocyte cfoinuanlt Protocol Exygen Research Page 117 of 217 : 634 : MIN 313/023622 Exygen Study No.: 023-076 Study Number : MIN/313 APlbanteolremt caoliutinets of the blood film MMeeaann cceellll hvaoelummoeglobin Mean cell haemoglobin concentration 2) Using citrate as anticoagulant Prothrombin time Activated partial thromboplastin time Blood chemistry H u n tin g d o n Life Sciences 14 (Day 91) Main group animals Conditions Anaesthetic Sample site Anticoagulant/Sample volume gF(neoonllteodrwaelcinaengdaeoenvsttesh)rne. siSgiaha.mt dpelpersivcoatliloecnteodf fuonodderantidghwtater Isoflurane. Retro-orbital sinus Lithium heparin/0.7 ml. All samples will be examined for the following characteristics Using lithium heparin as anticoagulant AAllaknailinneeapmhionsop-htraatansseferase (GPT) AGslupcaortsaete amino-transferase (GOT) BCihloirluebstienro- lt-ottaoltal TCUrrrieegaaltyincienreides Total protein ASPorlobdtuieumimnine/lgelcotrbouplihnorraettoiogram PCohtlaosrsidiuem PChaolcsipuhmorus Final Protocol Exygen Research Page 118 of 217 : 635 : MIN 313/023622 Exygen Study No.: 023-076 Study Number t MIN/313 H u n tin g d o n Life Sciences LDH + Iso enzymes cBSroVeraNbtiitnoel dFehhoysdprnoogkeinnaassee 6.7 Urinalysis 4 (Day 29) 14 (Day 91) Animals Satellite group animals Main group animals Recovery groups animals Conditions and water deprivation.. All VAoplpuemareance PSrpoetceiifnic gravity KGelutoconsee BSBolioldioriuudmbpinigm(beilnetspigments) CPohtlaosnsdiuem The deposit, obtained from centrifugation, will be examined microscopically by LM fo r Epithelial cells CLECearryyusttscshtoarcolsyctyetses OSptheermr aabtonzoorma aanldcopmrepcounrseonrtss And by SEM for CCarystsstals Method references will be detailed in the final report Final Protocol Exygen Research Page 119 of 217 : 636 : MIN 313/023622 : 637 : MIN 313/023622 : 638 : MIN 313/023622 : 639 : MIN 313/023622 Study Number : MIN/313 TABLE 1-Pathology procedimi lAAbdntcoarmilialities [Caecum [Htrdcrnplanta ventricularregionali II-ivcr (section from all m ajor lobea) n " djor lobea including meaenteric ttacbeo-hronchial N asal turbinate (3caIundvaelliti' IOvaries (au bm an d ib u lat/iu b l Exygen Study No.: 023-076 H u n tin g d o n Life Sciences Apomodc bodlc ITettet (PAS m in in g Jhyroid witti parathvmiri. jTacbea'b(liandcdluedring b tfu rert, ) utenti with cervi V agin. ------------- S-Uion,toincludepelvice p S t ^ T ^ ^ " dtnicroscopleilly Final Protocol Exygen Research Page 123 of 217 : 640 : MIN 313/023622 Exygen Study No.: 023-076 Study Number sMIN/313 H u n tin g d o n Life Sciences 8- PATHOLOGY 8.1, L igh t m icroscopy Animate Premature deaths All from all Terminal sacrifice AH Main and Recovery animate AU specified in Table T Peer Review 2. Extension of Initial examination E ST *""" consultation with the hssues considered to exhibit a reRac"ti0oVnetloytreatment2inaGndro3upl"olled at termi Sacriflce for Any such requirement wl be documented in an amendment to the protocol. processing or staining techniques. using additional Sponsor; taken by a Pathologist with the Report : Full photomicrograph; report if required. Exygen Research Pinal Protocol : 641 : Page 124 of 217 MIN 313/023622 Exygen Study No.: 023-076 Study Number MIN/313 H u n tin g d o n Life Sciences DATA TREATMENT 9*1. Statistical analysis Data-types The following data types will be analysed at each tinrepoint separately:- fbbolooododydwccoehniegsmuhmti,sputrtsyiionangn, gdoavhienarsemaopvapteroroloappgripyar.toepsrtiuadtey spteurdiyodpse.riods. pathological findings, for the number of animals with and without ewachherfeinadpinpgro. priate. Methods eFaocrhctarteeagtoerdicgarloduaptav,etrhseusptrhoepocrotinotrnool.f animals will be analysed using Fisher's test for Fwcboeoimtlrwl cptehoaeenrnintsitonbhnueesocguworsomhduepapratesar.n,edBeUcawserisintstlgheartttyteh'.ssettsceodstnewtpreoinllldgferiornsuttpob,neitnahcpeoporlpiueotdcraottominteegsoatfdtBhjueasrhttmolemettno'tsgfteoenrsetm,ittuyrleotaifptevledargiraonucpes 10. REPORTING Study progress Draft final report Authorised final report Periodic verbal and written updates on study pRanroodugtarietnsteesrswmyniilnolapbtseiiospnrreoopvfoitdhrteesdiwnb-iylllitfbheeepsShetaunsdtey.afDteirre1cwtoer.ek For review by the Sponsor After approval from the Sponsor. Routinely reports are supplied on A4 paper. The following numbers of reports are supplied. Type ofreport Draft report Authorised final Photographic report fif any) Double-sided DSionugblele-s-sidideedd BouNnudm ber of cUonpbieosund addendumfamendment to the final report as a formal hi the absence of ongoing communications, Huntingdon Life Sciences reserves the right to ffiinnnalliiCsPe, esiuiicahh aann eAsaiviigwmennnStaa, niuandllillis-m--s---ua--*et-e---rt--h^iVa-e.*.ls-Cfi-_wn____a_'iY1llll_r_tbe_____pe__._o._.t_r._rltanfrn_s_o_f_em__r.rtehdIist. ostut.hdey six mon arc-hi.ve. thAMs nayf. temr h.AissusOnuUpet.i .wonlf.t UthrteweqUdurelaus"fltlts.*. foIInlrl mamoednifdicmaetinotn(so,rcnoerwrecsttiuodnys,oars aadpdpirtoiopnrisatteo)tahnedfiwnailllrbeeposurtbwjeicltl tboentHheHisfutnbpjaeicctoosfta formal report Final Protocol Exygen Research Page 125 of 217 : 642 : MIN 313/023622 : 643 : MIN 313/023622 Exygen Study No.: 023-076 s5EfK,SEP.w1i9u.n2u0j02I t1a0:*12AtNHAlM/uEDivICAiLva220 2Eu 02 rO$Wt* Fax Note 7671 ^TtH ri HAHBb t Y FAX HEADER SHEET FAX:014S08922 8f P.OOI Huntingdon LWiofrkeingSfo cr aiebonnercfuetus TOTALNUMBERof PAGESINCUTONOTHISPAGE; ""'""'io>uTMtiActar,plsuccomau., Tel:-MS(0) 1480I9224 CaOttMePnAtNiYo:n OF: j>rR GrastBWiaren R|ha Exyeen Research, FAXNUMBER; 001 814 272 1039 MESSAGE; fROM' Terry Kenny oaTE i ay September 2002 J17B73u}tenhoff(Fex 001 651 733 " S & t snumber MIN/313) f f l i . R - S . t recovery period (Study DoerDr Grazzini, Best regyds Terry Kenny Local facsimile machine; ++4444 1i44g8o0 B8992S02S780 RECEIVED TINT SEP.19. 11:----p-E- i******** PRINT TIME MSJSESP.1r9. ++11:1'4"PMmm Exygen Research : 644 : Page 127 of 217 MIN 313/023622 Exygen Study No.: 023-076 1i?9.sePSiE, P.v *1i9t.i2ivC/021,110w:u!2AMIIlnunllA..uM/iEiDivIiCtALiva220 2Eu 02 FAX10M80892288 s s PSrtovtdoycNoluAmmbeenr dment Number j 3MIN/3I3 Huntingdon Life Sciences PERfXUOROoCTANKsrrr rnwvr IJruar; i./o o IA) TOXICITY STUDY BY INHALATION ADMINISTRATION TO CD RATS FOR 13 WEEKS FOLLOWED BY A 4-WEEK RECOVERY PERIOD Total number ofpage; 3 Number of pages for Internal distribution! Study Directo : T.J. Kenny, B.Sc (Hns.). Atchhai?,nflmesetnodtnhieenittu, td^dvelcoUtosdiVJn.-tfowmece,0nftiljll.,h.-ori*e` .^mplementatim ncw of .hi. *tetwnWil w underlined, AnIvn AMENDMENT APPROVAL For Huntingdon Jflli Esnnesf Ltd (ASututhdoyrDisierd^gbtyo;r^) For th* Spanior Approved by Due: RECEIVED TIIC SEP.19. ll12flM Pago 1 PRINT TIME SEP.19. 11:14M1 Exygen Research : 645 : Page 128 of 217 MIN 313/023622 : 646 : MIN 313/023622 RECEIVED TIME SEP. 19. 11S12PM fige 3 PRINT TIME SEP.19. ll:l4fiM Exygen Research : 647 : Page 130 of 217 MIN 313/023622 : 648 : MIN 313/023622 : 649 : MIN 313/023622 : 650 : MIN 313/023622 Exygen Study No.: 023-076 OCT, 24.2003 8:44AM MEDICAL 220 2E 02 PStruodtoycNoluAmmbeenrdment Number : 4MIN/313 HO. 2609 P. 5 Huntingdon Life Sciences PERFLUOROOCTNESULFONYL FLUORIDE (POSF; T-7661.4) TOXICITY STUDY BY INHALATION ADMINISTRATION TO CD RATS FOR 13 WEEKS FOLLOWED BY A 4-WEEK RECOVERY PERIOD ARdeadaitoiorun foofraanmaleyntidcaml emnetthodology; detail Amendment* M . Teatlubetance/metabolite analyeae SRaemcopvleer*yo(fDbalyoo1d23()foarndteSrautmel)l,itaen(dDaliyve2r9)wainnimbeal*co. llected at necropsy from Main (Day 921. B aolmothop*dleS*wpoailnlllsobowere.rdemtoodvoedt aattrnooecmrotpemsypebryatcuarredaiancd/atohredsceppaurnactteudrleerinutmo ftruobzeen(purpiotroto4dmeslp),attchhe 2Uaf8rt/ei2nr9ecfcoromolmlpelcSettietidoelnoUvoteefranunirgiimhntaatltyreaaliemiiUpMeadraaoinmneaDtneedry!R2a9ea.caoavye.ryOgvreorunpigehattsDaamyp9le1*awnidll1b21e wcoillllebcteedfroDzeenv Thefrozenaamplee will bedeipatched to thaSponsor's Principal Invcadptorfaranalysia. Principal Investigator : Dr RichardGrazzmi Addreia : HS3PUt0xASa3ytAg8e1o6RCn8ao0Ral1laeeaagreeeahrcDbrive Tel No. Fax No. 001814 2318032 001 8142311380 RECEIVED TIME OCT.24. 9:48flM Page 2 PRINT TIME OCT.24. 9:50flM Exygen Research : 651 : Page 134 of 217 MIN 313/023622 : 652 : MIN 313/023622 Exygen Study No.: 023-076 OCT. 24. 2003 8:44AM MEDICAL 220 2E 02 NO. 2609 P. 7 PSrtuodtoycNoluAmmboenrdmontNumber ::M4 IN/313 Huntingdon Life Sciences AUmolewill be analysedforPOSP. PFOS andPFOA. rcvitlon. current tSoimwpnleninwYfllMbeiann.alysed forPFOS end PPOA accordingto Exveen method BtM-023-071 in AoraenfnpdtyohlriAetv.neSrtpAhwoelnlrislrploabrrwo.ecdreAeasttsaaciinonrgpeeydleenvbodayfnitttnhbteeiolSyStppihiooeennaossonofrart.l'hysesresesapmoorfpttlewesitlelsnubdbesdtiaenntcilcuecdoaelnldadtaimosneatnwabialodlldbiteeensdthiunemrpeltasopsmtohnaes,isbutiruliidntyye RECEIVED TIME OCT.24. 9:48AM Page3 PRINT TIME OCT.24. 9:50AM Exygen Research : 653 : Page 136 of 217 MIN 313/023622 Exygen Study No.: 023-076 t\yg RESEARCH Precise Research. Proven Results. Page Deviation Number 1 Date of Occurrence: throughout study Exygen Study Number: 023-076 Protocol Nu m b e r M1N/313 DESCRIPTIO N O F DEVIATION 1. Am endm ent #4 ExM-023-071 Revision 1 Section 4.5.3 .e - accep ted recoveries o f 1 3 5 * for PFOS in Set 092002B, 1 4 2 * and 1 40 * for PFOA in Set 092002BR, 6 7 * for PFOS and 1 3 3 * for PFOA in Set 102102B, and 6 8 * for PFOS in Set 101602B. 4.5.3.C.2. Am endm ent #4 ExM-023-071 Revision 1 Section The last standard injection in Sets 092002BR, 092502B, and 100102AR w as not included in the calibration curve. 1-2. Deviation issued. tor example -AdCevTiaItOimNi iSMTiwAdK. SEONP revision. etc. 1-2. N o negative im pact on study. IMPACT ON STUDY Principal Investigator Signature Study Director Signature Management Signature (Sponsor) U:\FonnsiPROTOCOLi.OEVlATiON.doc Date Date Date Exygen QAU Review' 905/2002IS Dnve , PA 16801, USA v T. 800.281.3219 r:c8y1g4e.n2.7co2m.1019 Exygen Research Page 137 of 217 MIN 313/023622 Exygen Study No.: 023-076 PROTOCOL utviA iiu N Deviation N um ber Date of Occurrence: Exygen Study Num ber 0/3-076 DESCRIPTION OF Protocol Number: MIN/313 A five-point calibration curve was analyzed (dataset 102903A), giving a correlation coefficient of 0.982. The method states that a linear correlation of 0.985 must be obtained. A point may be dropped, however, if it 1s shown to be a statistical outlier. W hen the statistical outlier test was applied to the curve, the extraneous point did not prove to be a statistical outlier. The quantitation reports were then printed against the 0.982 correlation A deviation was issued. foLgaippJ? ;AdflvTiaIQfoNp l9asTaAd .KgEQNPfgvMon. Recorded By: IMPACT ON STUDY There is no impart on study since the analyte of interest was not detected in any o f the samples. Study Director Sigriatiffe tanagement Signature (Sponsor) U:\Focms\PROTOCOL_DEV1ATION.doC Date Date 7Jo'63 -DaZtie~ <H/L 3 Date Exygen Q AU Review /}h > 8/25/2002/5 Exygen Research Page 138 of 217 MIN 313/023622 Exygen Study No.: 023-076 APPENDIX B Analytical Method: Method of Analysis for the Determination of Perfluorohexanesulfonate (PFHS), PePn(eEtraxfdlyRuegocaeartnofLloMuicvoteeratroRnh,oeoeScsvdetuiarsNlnoufoonomn.ic1Eaa)tAxneMdc(iPdU-F0r(2OPi3nFS-e0O)7aA1n,)din Exygen Research : 656 : Page 139 of 217 MIN 313/023622 Exygen Study No.: 023-076 TITLE PeMrfeluthoorodoocftaAnnesaulylfsoisnafoteLr(itvPheeFrOD, SSeet)erarumnmdinaPanetdniotUandroienfcePafRelruefovluriosoioroocnthae1nxoainceAsuclifdon(PatFeO(PAF)HinSR),at . AUTHORS John Flaherty, Karen Risha, and Emily Decker DATE ISSUED November 20,2002 SPONSOR ^ 3M Med3icMalSCDt.eePnpataeurrlt,,mBMeunNitld5Ci5no1gr4p24o2-r01at-0e20ET0-o0x2icology PERFORMING LABORATORY St3a0tEe5x8CyoRgleelensgeRear,ecsPheAaDr1crhi6v8e01 METHOD NUMBER ExM-023-071 Revision 1 TOTAL NUMBER OF PAGES ' ' 43 Exygen Research : 657 : Page 140 of 217 MIN 313/023622 : 658 : MIN 313/023622 : 659 : MIN 313/023622 Exygen Study No.: 023-076 ExygenMethod No: ExM-023-071 Revision 1 LIST OF TABLES Table 1. Recovery Summary of PFHS in Rat Liver and Serum........ Table 2. Recovery Summary of FFOS in Rat Liver, Serum and Urine. Table 3. Recovery Summary of PFOA in Rat Liver, Serum and Urine. 20 21 22 : 660 : MIN 313/023622 : 661 : MIN 313/023622 : 662 : MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo: ExM-023-071 Revision 1 1. SUMMARY ' T((FPhFFisHOrSAe)p),oinrPtRedrafelttualoiivlrsoeoarc,mtSaeentrehusomudlfaoonnfdaatUnearilny(PsiF.sOfSor) reasnidduePsenotfadPeecrfalfulouroorhoeoxcatanneosiuclfoAnacitde Rceaaaocnlceucenastotldieoydmidnstuiiipoeswtlrsniuiisletsehhodi.enfd2gCPb1mTmEy8huHLlelsitSqoiop,aulfilcidePdemFrtpoceeOhhanthScaritotsarimenioaloennaeltd.xmoetgrxoPaQrtnaFcriuaptOticaohotnArynit/niitfsa(gaiSncr(aPadeMdteEidmoeR)exnMdctmraoa)ar.tfctosrtsPieddFwsgpHeaef.tScreot,rrmAoPamnFneaOedaltySrcytlheoa(anLrmdedCesadi/tPdMrFiuxoSOens/AtMwoaiSrtihesa) Tmmheeetthhpoorddopiwsohs1ei0cdhnlgimg/giivt(eposafratqsdu-epaqenurt-iatbtaeitliloiroennc(o)LveOearcQyh;fatohcrcePolrFodwHineSgs,tPtfoFoOrEtiSPfiAacnatdgiouPniFdsOeplAienc.eifsi)edfobrytthhies cTianonhsrdterreutswhmpeioleolnnredtbatsietcitoaoaln0tl.is1mlyenasittgseto/mmfgLdruee.staeetdcetr.iotnhFa(onLrO3aDllt)iamwneialsllybtteehseb, atlsheeevdelloonwotfehsent osaiingsean,laylbtitacosaneldositsoaennrdaatthridoe Trehciosvmerieetshodstwanadsadrdevdeelvoipaetidonussi(nagt 1r0atalnidve5r0, nsegr/ugm) araensdhouwrinneb.eloTwyp: ical percent Rcherpormesaetnotgartaivmes caarelibshraotwionnincuFrivgeusreasre4 tsoho3w9.n in Figures 1-3. Representative Page 7 of43 Exygen Research : 663 : Page 146 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen Method No: ExM-023-071 Revision 1 EXPERIMENTAL COMPOUNDS The structures for PFHS, PFOS and PFOA are given below CMhoelmeciuclaalrNwaemigeht = 3P9e9rf,luasorSohhoewxnanesulfonate PFHS is supplied as the potassium salt (CFbSOjTC), molecular weight = 438 PCFhOemSical Name Molecular weight = 4P9er9f,luaos rsohoocwtannesulfonate PFOS is supplied as the potassium salt (C!FnS03'Kt) molecular weight = 538 PMCFhoeOlmeAciuclaalrNwaemigeht = 4P1en3t,aadseschaoflwuonrooctanoic Acid Exygen Research Exygen Research : 664 : Page 8of43 Page 147 of 217 MIN 313/023622 : 665 : MIN 313/023622 : 666 : MIN 313/023622 : 667 : MIN 313/023622 : 668 : MIN 313/023622 : 669 : MIN 313/023622 : 670 : MIN 313/023622 : 671 : MIN 313/023622 Exygen Study No.: 023-076 4-5.3 Sam ple Analysis a. rIencjeocvtertyh,ecosanmtroel,aelticq.uiontto(btheetwLeCen/M1S0/MtoS 5sy0stjeimL). of each standard; sample,' b. SwtiatnhdtahredLs OcoQrrleesvpeolnodrinbgeltoowa)tmleuassttbfievienoclrumdeodreincaonncaennatlryattiicoanl lseevt.els (starting c. An entire set of calibration standards should be injected at the beginning of a bmassealetumtgesirfptnnolbnaleleitsoinvtwghe(ee,taodnfaidnbrasyactetcacnotnahtuidlernibeltearnassfdtteoiitoronnjfoeaafcsttsacisoaneamncdlioabpinnrrldeadastissoeisannte.mttespIrotnslaefpneesdieretasxhtre.teddrrsaccaamtpespdaer,yocsxtabiamlenibadirtanaerctldiylosun)ed.vesedtarynAadts5a-rt1hadn0es d. rrRnTseateheanscsenpgeudoesclan.stosrasndermcyse,cansuydhtrriovabluuteeitl,oedqnbubtahaorsenafect.edisktaaaecmotthenprdselaesuthmpspeopttnoolpscee/g1fsaio0vko%retfiafaotirhceuareatetsisrioodepnsefoi/ndctehosuaeenecthcwrfouoilarutvhninseiadnldbyietytnhetee.eerxamstcrtTihaannhpesdeodaalmarfstdrtpioaolmncenud.sratvherIdeetf e. Fortification recoveries falling within 70 to 130% are considered acceptable. f. Samples must be stored refrigerated between 2C to 6C until analysis. g. lccwSaeaonashlnamsiiblccytperhhtalneaetptnisreoraeatinthntkieosesntwnaLtainhrooOidencfaQhdrttdheaiesmtenietwdcehctaeigelwlrldriebbinalaroelattetrbtpirehoeeptenahorkcaerssontptearoaodrnrrerdeatseesapddqroNdeunastQaedslcai(nttNronegedoDtatdhonqee(ratunlelapooycnewtttteeaieddkfrseiseattateblcteeclonetstnhet)si.dceote)nh.ncaottnrirSamrtteaihesmoepntpohlolonaefwtdsitaenhirsngeet Ti51n00hsenaengraud/ngma5loy0afsnnPidsgF/puOgeriSronffoea.rPnmdFTeHPydpFSidOciuanArlirncianhgtrrltoiahvmteelarmi,tvoee1grt0rhaaoanmndddsd1ce50av0neanlnbogdephm5fio0Leunnnotgdf/imniPncFLlFuHoidgSfeudPirnFefsoOsre4Str-iu3faim9cn.a,dti1Po0FnOasnAadt Exygen Research Page 16 of 43 Exygen Research : 672 : Page 155 of 217 MIN 313/023622 : 673 : MIN 313/023622 : 674 : MIN 313/023622 : 675 : MIN 313/023622 : 676 : MIN 313/023622 : 677 : MIN 313/023622 : 678 : MIN 313/023622 Exygen Study No.: 023-076 ExygenMethod No: ExM-023-071 Revision 1 Figure 1. Calibration Curve for PFHS CCCCRauooelrmesivbfpepfrolaodtntyuiesopnnenedtt;0yc1Lu/pirnDenv:aeeemEat:erxer1,tm:Oe9Pri1rnnFi6gaaH^iltni8SSo:nt*Ed;x,x0Ad+.9ur99ed.a6e14,46W153e4ighting: 1/x, Axis trans; None Response* i ngtoiL Exygen Research Exygen Research : 679 : Page 23 of43 Page 162 of 217 MIN 313/023622 Exygen Study No.: 023-076 ExygenMethod No: ExM-023-071 Revision l Figure 2. Calibration Curve for PFOS Compound 2 name: P F O S Coefficient of Determination: 0.997009 Calibration curve: 3211.30 * x + 48.9285 - - Response type: External Std, Area Curve type: Linear, Origin: Ewlude, Weighting: 1/x, Axis trans: None 1.62e4-> 0.0 o!5 l!o " L5 ' ' 2.6 ' ' 5 3!o ' ' 3 ' ' 40 40 ' ' 50ng/mL Exygen Research Exygen Research : 680 : Page 24 of43 Page 163 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen Method No: ExM-023-071 Revision 1 Figure 3. Calibration Curve for PFOA Compound 1 name: P FO A Coefficient of Determination: 0.995946 Calibration curve: 31270.9 * x + 3675.36 Response type: External Std, Area Curve type: Linear, Origin: Exclude, Weighting: 1/x, Arfs trans: None 1.66e5-i Response- o!o ''0.5 '"l!o " 1.5 '2 .6 ' ' 2.5 s!o '''3I5 '''0 ''4I5 ''5ing/mL Exygen Research Exygen Research : 681 : Page 25 of 43 Page 164 of 217 MIN 313/023622 Exygen Study No.: 023-076 ExygenMethod No: ExM-023-071 Revision 1 Figure 4. RCeopnrteasineinntgatPivFeHCShromatogram of a 0.1 ng/mL Standard COOIOM, a i ngftnL PFHS 2tJun40021S:02:30 ~v*'V ...... ,.t.iu Figure 5. RCeopnrteasineinntgatPivFeOCShromatogram of a 0.1 ng/mL Standard ra*2S 0M ,0.1 ngftnL PFOA and P F06 07M02A-1Q1 8m (Mn, 2x2) WMw*. WO M O to o ICO 0.00 7 . &00 1.00 Exygen Research Page 26 o f 43 Exygen Research : 682 : Page 165 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen Method No: ExM-023-071 Revision 1 Figure 6. RCdepnrtaemsemntgatPivFeOCAhromatogram of a .1 ng/mL Standard COOSOM, a t noM. PFOAaid PFOS Figure 7. RCeopnrtaesineinntgatPivFeHCShromatogram of a 0.5 ng/mL Standard CM210*, UligftiiLPFHS 0421024-103 8n (Mi, 2x2) UXH Exygen Research Exygen Research : 683 : Page 27 of 43 Page 166 of 217 MIN 313/023622 : 684 : MIN 313/023622 : 685 : MIN 313/023622 Exygen Study No.: 023-076 Exygen Method No: ExM-023-071 Revision 1 Figure 12. RCeopnrtaesineinntgatPivFeOCAhromatogram of a 5.U ng/mL Standard Figure 13. RAenparlyezseedntfaotrivPeFCHhSromatogram of a Reagent Wlank Sample MzlOM'lOC 8m (Mh, M l Exygen Research Exygen Research : 686 : Page 30 of43 Page 169 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen Method No: ExM-023-071 Revision 1 Figure 14. ARneparlyezseedntfaotrivPeFCOhSromatogram of Rfeagent Blank Sample figure 15. ARneparlyezseedntfaotrivPeFCOhAromatogram of a Reagent Blank Sampi Exygen Research Exygen Research : 687 : Page 31 of43 Page 170 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen Method No: ExM-023-071 Revision 1 Figure 16. RAenparlyezseedntfaotrivPeFCHhSromatogram of a Cntrol Liver Sample Figure 17. RAneparlyezseedntfaotrivPeFCOhSromatogram of a Control Liver Sample 1.00 2.00 100 4 100 100 7.00 100 10 Exygen Research Page 32 of43 Exygen Research : 688 : Page 171 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen Method No: ExM-023-071 Revision 1 Figure 18. ARneparlyezseedntfaotrivPeFCOhAromatogram of a CbntroI Liver Sample Figure 19. ARneparlyezseedntfaotrivPeFCHhSromatogram of a Control Serum Sample Exygen Research Exygen Research : 689 : Page 33 of 43 Page 172 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen Method No: ExM-023-071Revision 1 Figure 20. ARneparlyezseendtfaotrivPeFCOhSromatogram of Control Serum Sample 1.00 !L00 3.00 4.00 8X0 6.00 7.00 .X 9.00 10.00 t t Figure 21. ARneparlyezseedntfaotrivPeFCOhAromatogram of a Control Serum Sample Exygen Research Exygen Research : 690 : Page 34 of 43 Page 173 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen MethodNo: ExM-023-071 Revision 1 Figure 22. ARneparlyezseedntfaotrivPeFCOhSromatogram of Control Urine Sample 070MZA-134 3mfl.tn.2x2) 0*-JuW00*M&M Figure 23. ARneparlyezseedntfaotrivPeFCOhAromatogram of a Control Urine Sample 0T08C2A-1W Km (1* 1, 2x2} 1.00 ' iO ' i o o '' 4.00 " ' 00 ' 1 MO ' ' b b Exygen Research X Page 35 of43 Exygen Research : 691 : Page 174 of 217 MIN 313/023622 : 692 : MIN 313/023622 : 693 : MIN 313/023622 : 694 : MIN 313/023622 : 695 : MIN 313/023622 : 696 : MIN 313/023622 : 697 : MIN 313/023622 : 698 : MIN 313/023622 : 699 : MIN 313/023622 Exygen Study No.: 023-076 Analytical Method: (MPOeotShfFoP)deironfflRuAoanrtaoUloyrcsitinasenf,eoSsruetrlhfuoemnDy,elatFnelrdumoLriinivdaeetriobny GC/MS (Exygen MethRoedviNsioo.nE2x)M-023-071A, Exygen Research : 700 : Page 183 of 217 MIN 313/023622 Exygen Study No.: 023-076 TITLE , Method of Analysis for thReatDUetreinrme,iSneartiuomn,oafnPdeLrfilvueorroboycGtaCne/MsuSlfonyl Fluoride (POSF) in AUTHORS John Flaherty and Alan Sensue ' DATE REVISED August 30,2002 SPONSOR 3SMt.BPCuaoiulrld3p,iMoMnrgaNCt2ee25nT05to-1e2xr3Ei3c--o03l22o2g0y PERFORMING LABORATORY St3a0tEeSx8CyoRgieelensgeRea,recsPheAaDrc1rhi6v8e01 METHOD NUMBER ExM-023-071A, Revision 2 TOTAL NUMBER OF PAGES 34 Exygen Research : 701 Page 184 of 217 MIN 313/023622 : 702 : MIN 313/023622 Exygen Study No.: 023-076 Exygen MethodNo. ExM-023-071A Rev. 2 TABLE OF CONTENTS ' MTLL243156......AIIASSBMT3TC33344444C444SNESL............aHa123413425678AUXOOEEfl............EcGeMPTFFu333444444OEMPtFBSCSQAPTSEHEyTF..l.......Mrltqe4aa54455445aFiaRhucM.IoaeImAOrmmu..t..t......CeacGpn.A3w12If12i1243cC.imoMnoqBEeD.pdap...Ahp......U.ROntrjr.DllaNmRLii.t.mCSSLeaeEFSSACLGcstY..rRaN..atEiTeea.daeotSeaN.PA.niaia.auCo.t..Eqrmvl.oTnltsrS.l..incrg.tsAuiT..nc.Atiou/..entoSuo.b.E.e..c.ibM.prm.k..a...nr.iAfPas..c.rNpea.....rrlNo.li..C.....Aaa.neas.ePe..cmyS......L./.C..fD....mt...oTdtd.s..ar...s.R..A.in.i..U...S..i..s.loSri.t.C.o...S....t.pSa.fu..siO...iS.i...nt.e.n..yr.o..n..o.t.n..alO.l..tu.......i.Ua.ePr.e..sy.V...in...nr..gn.C..i....S.p..lo..rtr.M..r.....as..Ad..Pye..e..i/...A....pe..unt....i....O.a....a.ms...a.P.....s...pCA..Prnl..........L..r.i....n....i.v.p......L....as.da..O........e..a....n..a....d..e..e.......r...l.I......l...s........n.aS...a.y.Ur......a..E.i....P.................a.b..l.d..t.....s...r......o......S.y....Ni...r....t.....rdi...............o..i...ol...O..a..s.s.............ns...u.....D..........n....i.c.t.....................g....i.sp...t................e..........oS......i...............1e............o....d..C.........n....................r......................n..u...............a.......o.................S................s..r...t...............n.................i,..e....t......................n......a.....d...............s...............................n.g...........i................................t...............d...................i...:....C.......................o........a..................................................r..on.......................................d.....................s..n...............................................................Sd...................................................................i.o................................t...........................l.........i......................u............o..................................................t................n.................i....................................o...........s...............................................n............................................................s..................................................... .-....234 ..5 ..6 ..7 ..8 ..8 ..8 ...8 ......111.....110998 .11 ..1112 ..1122 ..1133 ..1154 .15 .16 ....11117977 Exygen Research Exygen Research : 703 : Page 3 of34 Page 186 of 217 MIN 313/023622 : 704 : MIN 313/023622 : 705 : MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071A Rev. 2 1. SUMMARY ' TPGehCrifs/lMuoSrre.opoocrttanedseutalfiolsnyla FlMuoertihdoed(PoOfSFA) nianlyRsiast Uforirne,thSeeruDme,tearmndinaLtiivoenr boyf AQspnueaacnltyrtoisfimisceaottrfiyohn(eGadCosf/pMaPcSOe)SgaFnasalyiisssiusas.ecdcotmo pdleistehcetdPObySFgiansracthurroimnea,tosegrruamph,yan/d lmivaesrs. Tmmheeetthhpoorddopiwso2she.i5cdhpligmg/imviteLosf(afqodureaqsneutraiuttaemtioraenncd(oLvuOerirQnye;)athcocero2lro.d5winpeggst/tgfoo(rfEtoiPfriAlciavtegioru)nifdsoeprleiPncOeifsSi)eFdf.obrytthhies Tp2cuehtrroivcsee1mn2its.ertsehhcooodwvenwriiaenssFadiregevuserhleoopw1e.ndRiunespTirnaegsbelrenasttaItu,ivrnien,ceah, nrrodamtinaset.orugAmrar,mepasnraedrseernashttaotlwiivvneeric.nalFiTbiygraputiricoeansl : 706 : MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071A Rev. 2 2. EXPERIMENTAL COMPOUNDS The structure for POSF is given below. ' MPCCCOAhhoeeSlSmmeFc#iiucc:laa3all0rNF7Wo-a3rmem5ieg-u7:hlPta::erC5f0lsu2FonrSooOctFanesulfonyl fluoride (POSF) o CF3(CF2)6CF2- S - F o Exygen Research Exygen Research : 707 : Page 7 of34 Page 190 of 217 MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071A Rev. 2 3. CHEMICALS AND SUPPLIES 3.1. Chemicals Chemical Methanol (MeOH) Grade - HPLC - Source EM Science Catalog No. MX0475-1 Standards SPFeltuarfonlrudiodarerod(oPcOtaSnFes)ulfonyl Lot Number 15721HQ Purity (%) 98.6 Source Sigma 3.3. E quipment and Supplies Equipment BD21lO02ais-5mlmap-nLmoLcsLheaae,bmaaalmednbsaegbplrleyaargctsiglsecalamsvaslsiias(vcldbrsiiao*oslpptstillpaeeystsat(3le0a-s1t000.0p0L0,11g0)0-200 pL) dCSGitlCsaapns/MosdsaASarbdpslyeliapstbteuetbemsqeausniedptmcv.o)elnutm(gertaridcufaltaesdkscylinders, LEAP Technologies Combi-PAL autosampler Supplier vaTrDie.ocrKKMuuhLsiimnemmeostmatubbllpoeplloeegrpnildeiesrs various suppliers AAsssseeddcceettssiiooccrrnniibb44ee..53dd..iinn Nwifoatstheed:yetEceaqrmnuiibvneaeldeshntoot wmbenat1teo2ripmalrsLod;muthacyeesbesaevtisisauflbasscwttioteurryteerudessfeuodlrtfstoh. ro*tsheAescmptueeactlhifhoieeddavdianslpitdahacitesiomvnoe.ltuhmode 3.4. Preparation of Standard Solutions Analytical standards are used for three purposes: 1. uCseadlibtoractaiolinbrSattaentdhaerdress--poTnhseesoe fstthaneddaertdesctaorreupsreedpainretdheinanmaelythsaisn.ol and are Exygen Research Page 8 of 34 Exygen Research : 708 : Page 191 of 217 MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071A Rev. 2 2. LcdcooeantnbectorremronalittnmroaeratyitaorninxCas.loycntoitcrrraoellsrpeSocpnoidvkieenrsgy.t-oLatThbheoerLsaetOoQryfoacrtnoidfnitcr4aoxtlioLsnpOsikQe.asraeanrdepparerreeppauarsereeddd tiaont 3. MssaammatrppillxeesSmapatitk4reixxs L-onOTaQhne.asleMyftioacrtartliifxriecscapotiivkoeenrssya.arree purseepdatroedevbaylusaptiekitnhgeienftfoectht eoffitehlde Tcohrereacbtsporloupteorvtoiolunms oesf soofltuhtee tsotasnodlavrednst maraeymbaeinvtaariineeddb. y the analyst as long as the 3 .4 .1 . S to c k so lu tio n Pwd2soireleCluiupgtttaehiooritenno6g(a1Cinno0au0aintnmd1d22Lii05sv0-wiamdsmiustLahigglamnmoseetfdbothectaahrknngeaollsmaylostailsinuncbtauaioloftan1tscl0steta0u)no-ridmefsarLt'r~osd2veb0o(xe0clpuo0simtrrorapeertegictordt/ienmcidndLfalfaatoesfrrk.oe.rfpruiTPgrOhietreySa)Fstotoarbncaydkt 3 .4 .2 . F o rtific a tio n / C a lib ra tio n S ta n d a rd S o lu tio n s a. PPmrOLeSpvaForebluyamafedbtdrriticinfgficl~aas2tik5oanmn/cdLabloirbfirntahgteiuo~pn2ts0ot0avn0odplaugrmd/mesLowlusittthoiocmnkeostohfla1un0toi0ol0.n pingt/omaL5fo0r b. P5an0red0p/,oa2rre5o0tth,hee1r0fro0erm,ti5afi0icn,aintaignodnfos2tra5tinfdipcagar/dtmiso.Ln/cfarloibmratthioen 1s0ta0n0daprgd/msoLlusttiaonndsarodf El2i.vx5earmpg(po/mlre:1L0)F0fiovpreLtimfoicifacstreioorlnuit.mersoroufrtihnee)5i0s peqgu/mivLalesnotlutotioan2s.5pikppedmin(2to.50p.1g/gg oorf Sgdlataotsersepbraelolptftalorerestd)if.iacta2tioCn stotan6daCrdfosrolautmioanxsiminuamrepfreirgioerdatoofr o(inne1y2e5a-rmfLroammbtheer Nmoatye:beAprdedpiatiroendailfcnoencecsesnatrrya.tions of Fortification / Calibration Solutions Exygen Research Page 9 of34 Exygen Research : 709 : Page 192 of 217 MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071A Rev. 2 3 .4 .3 . C a lib ra tio n S ta n d a rd s * hGsaomperCapad/0rMlos.l1ppSaaricmgaaetno.erauaElantymxtslaioi(smvutyecnprpat)lie,lcoisbafeorlvclafyaotcipnoa5otnlrrioabpsltrtiLaamntn)giadotianrtnirhtxsdoeta(l1nesav0tdae0asnlredsduaaLllareerddvef,oedlvraseinrataadelrtremsiwsneihrhjneuoieccmwdthinnbagcanyosdns1frtpoaailmtiklnoiuLswnrgisnao:neaf In(intiga/lmCLo)se. 15212500505000000 VSp(oMil555555kuLimn)ge HVe(aomd1111l11us222222Lpm)aece IVn(jomelcu111111Ltmi)oen Injected Amount (Mg) 000000......000241241120120 Exygen Research Exygen Research : 710 : Page 10 of34 Page 193 of 217 MIN 313/023622 : 711 : MIN 313/023622 : 712 : MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071A Rev. 2 4.5. Quantitation ' 4 .5 .1 . G C /M S S ystem a n d O p era tin g C o n d itio n s < Instrument: HChewrolmetat-tPogacrakpahrd/mmooddeell56987930mSaesrsiesseQleacstive detector Column: RestekRTX-502.2,60 m x 0.25 mm ID, 1.4 pm df Oven Temperature: Hold at 40C for4 min., ramp 20C/min. to 100C, hold for 0 min. Injector Temperature: 220C Transfer Line Temperature: 220C Camer Gas: Helium GC Head Pressure mr5epmins.ai,ifnroadrme0rp.2o-5f8t0mhepinsa.in,/maralyimnti.pctao8l03rup0nsp.i/smi,ihno.ltdo a6t03p0spi,shi ofoldr 0.5 GCFlow Injection Mode Varies with GC head pressure and oven temperature Splitless Injection Liner 4 mm ID straight glass Injection Purge Delay 2 min. Purge Flow to SplitVent Injection Volume Electron MultiplierVoltage 10 mL/min. 1 mL From ATONE+ 200V Scan Mode SIM " Monitored Ians m/z's 69 (quantitation ion); 131,219 (qualifier ions) Dwell Time 75 ms Integrator Hewlett-Packard ChemStation Software Retention Times -3.4 minutes Total run time -7 minutes Exygen Research Page 13 of34 Exygen Research 713 : Page 196 of 217 MIN 313/023622 : 714 : MIN 313/023622 Exygen Study No.: 023-076 Exygen MethodNo. ExM-023-071A Rev. 2 4 .5 .3 . C a lib ra tio n C u rve P ro ced u res ' a. Psa(clfmleiaooamrvvitellrenuioepbr8utlui)ari0nt.pnoraejettnrseCAiecooacp)iftn,natifatoelt6rmiocsren0botda,t"aranhnaC)n,ttteusdrhie(iooaaventalnlhritlldaoeyemvsldsit(tiaiaayhrsn(talnrercjicndieanxoiGgcapsgnrtipCen(dd1etcgs/iihd0Motsie)b0nfohSrydhneosp.ieeaamtsLadmitpoIedf(identsfkhhuopetieeadosnraamicgntr7leeao(og0dhatwuvne)Caniseaafet)saLtol.retporuEwdplmf()AehravohipPfcepaepohlnraCrriddoascosxtto(merapiananmapbvttdcapiaoea-uirtPlnreorud(isAlx1nmyiatLe)moenmfoaaooLtaturuhepf)trel0opysm.sort)1hoaafiimnpgntgrdhhupiaraterleereatsdeesrtt b. ptUsneahoxreuseefcametlktwugobwdeateaaenrerrleideeog.nrahafufttcrvAmeeoaeddmnlbriyseblfuirprtnchasoreatefialceoirsacabntlacsaritlahsbnacttdrnauiaaoandltnarnidadaotraislsndorytdinatcnsesnujtoedatrbhcnfvayatrdeettdhasdlmrei.ffdnooaecurycaanorqlbidnubercaerteaengoxnttriicetbotrlasneausttidiioacoeonundns.rtvmuaueLtssu.iiisisnnnttigeHgcnaaoor1Hlwt/sxPoeteauxvwnOtceldeeireayie,grrrdtdnhhm2itseci0tanua%tygrtoviotbeooaneslff c. The correlation coefficient (R) for calibration curves generated must be ast0pap.n9rd9oa2pr5rdisa(toeRr2tshtee0p.rs9e8lme5v)ua.snttIsbfeetcoatlfaiksbaermantipotloensrasedhsjouuulstltsdibfnaesltrlreu-omaunteasnildyt ezoepdthe.ersaetiolnim, iatsn,dththene A typical calibration curve for POSF can be found in Figure 1. 4 .5 .4 . S a m p le A n a lysis a. Ptvmcasthhtouiraaeraentnenolptsedrusaaoaaimarmslrmel,dlipynpsclseuaeloieotmtnncierlnjd.uspeftitlocoatieiiortntosantti6nhonbh0eiejyendeCattcshwodate(i(smeohttpihhnegeaGeea,hctaCsteisehlnyed/ivegrqMa)iiulanve(Slogiffd.atooelrIrs((ii1cfysslanisahvmpctepeeeopcpLmarneer)t)dsode.so)dxioatriihftrmooymeIen,faaa7eetdsc0deapushlspisy(Cukihsanr)etec.iafgnaeaontgnudesadraaa(mr)fpdomLpfp,roErilsonsreAaepu(mvrPratuieippaamsptllCee.r,o(oavaxmrAnoteidlmbcfuto8iuema-0vPrrtieeeAntlrChyoeyL)e)),f, b. wStiatnhdtahredLs OcoQrrelesvpeolnodrinbgeltoowa)tmleuassttbfeiviencolrumdeodreincaonncaennatlryattiicoanl lseevt.els (starting c. Asent efonltliorewseedt boyf caalbibartacthioonfsstaanmdpalredss. shHoouwldevbeeri,najebctaetdchatmthaey bneogtincnoinnsgisot foaf Exygen Research . Page 15 of34 Exygen Research : 715 : Page 198 of 217 MIN 313/023622 : 716 : MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071ARev. 2 astpapnrdoaprrdisatoersthteeprselmevuasnt tbseettoakfesnamtopleasdjsuhsotuilndsbtreurmeaennatlyopzeedra.tion, and the 4.7. Performance Criteria ' bTtheheeencfouomsllemodwefnioncrgetmhtwiesnomtceortfihtaoenrdia.alymsiusstwbheenpeursfionrgmaend iansstarusmysetnetmatisounitsaebti-luitpyttheastt,hbaesfnooret First Criterion: PdoepretteipmramriezineaebniydfcthihnaejneignctisntraguimGnCestn/rMtuhmSaesnsattdaoenpqdeuarraadtteincsgoernprsaeirstapivmointeydte.irnsIg.f tthoistchreiteersitaimcaantendotLbOeQmetto, Second Criterion: . cRLGcroOueietnnQefefra,iircoasiunteeepntisatotmcoofafesltttiad,hbneseradatemtahirromipdgnlsihencseoausmfttrifvoaicenvyoefbn(oRocerer2at)nmhntaeoroalfyrateiznaoeactndloyl.nelteecavseatennlt0dra.t9ooti8bo5tbnaeiflneoviranectllhsliun,edefreaaodnrmarleiyngatrteet.ohsrseibOoeannlncowaewlyittsthhhiiseas. 4.8. T ime R equired for Analysis miiOnnanjeatercpiptpxieorrsonspxsoii,knme2ca)0atwenfliiytleall2ktdaehksaoeausmarepspt.ploerTfos,2xh0ie1msGmaatmCealt/pyMrliex5Sshbtaohlnauranorlskuy.,gsih1stohlaefbtsoharematspoelrtey(pccrooenpntatarrioanltiinosgpni6kperso,tacanenddduarrde1 5. CALCULATIONS a. UpesaekEqauraetai)onu1sitnogcatlhceulastteanthdearadmocuunrvteof(PTOrieSFwfeoiugnhdted(inlpinge/amrL,rebgarseesdsioonn Equation 1: Analyte found (pg/mL) = (Peak Area - Intercept x DF Slope DF = factor by which die final volume was diluted, if necessary. Exygen Research Page 17 of 34 Exygen Research : 717 : Page 200 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen MethodNo. ExM-023-071A Rev. 2 b. EPqgu/gat)i-on 2 was used to calculate the amount of P'OSF found (in ug/mL or Equation 2: ' -- Total Analyte Found (pg/mL or tig/g) = Analyte Found (ug/mL')x Standard Volume Added (m l.) SW (g) or SV (mL) . SW --sample weight, SV = sample volume c. Ewqituhaktinoonw3nwamasouunstesdotfoPcOaSlcFuplartieorthtoe epxetrrcaecntitonre. covery for samples fortified Equation 3: Recovery (%) = Total Analyte Found (Augn/amlyLte*)A-dAdendal(yptge/mFoLu*n)d in SamnV (,, o/mi ), i n n * = (or pg/g) tFcShoaoarmrtreaprsrelpeeposolenirsdntsiinnwtghghaipnacunhtrhappleoyeLstaeekOss,rQeaftrweieenilltddileobtsneeacmrtteiemppdloeearsttewitdhnileal swcbNoheriQcrrehe(snppnooootrntqdepudienaagnaktsisafniNaaabrlDeylete)d(.enretoettecntdetediotenacttteimtdh)ee. Exygen Research Exygen Research : 718 : Page IS of34 Page 201 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen MethodNo. ExM-023-071A Rev. 2 6. SAFETY ' Trhlaeahbanegoderlaaninnttosgarlyysbstceatofnoasdtrhaseo,rduspsaldefaerfnrtoyedragmdrleaiastnhgsgeeesnt,mthsai,anstidenrmcgilaleuoltdvhsieonasdfg.e. twyoUdrkasitenagusihnneivefteusrmsfaeolrhpoaroleldcsastuaatnnioddnawsrdeswarhainnegdn Exygen Research Exygen Research : 719 : Page 19 of34 Page 202 of 217 MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071A Rev. 2 Table I. Recovery Summary of POSF in Raf Serum Summary of Rat Serum Recoveries Sa m ple Trial #2 #1 Sam ple Injected Sample Area Std Injected Amount (pg) Counts Amount (pg) 00..11 650036447552 00..11 0.01 46925 0.01 Std Area Counts 553366440077 51030 % Recovery 9141.34 92.0 : 720 : MIN 313/023622 : 721 : MIN 313/023622 : 722 : MIN 313/023622 Exygen Study No.: 023-076 Exygen MethodNo. ExM-023-071A Rev. 2 Figure 1. Calibration curve for POSF f 0Q#-*^JQ5-4 5.oc**qcs- 3.ftO+Q05h 2.0fi-fOQS- 1.90MO9200Imwint oSSitDapecon*<*r**2>l,190+.*Q*Q3 *CAUwrCv*-MJ.bt9?w**l0r0(l3/* >\ KCatliittodafccliAoWnfttTCUi\HSCHSMt\y3\dlfafltTc3diQi DT3uV*POMSf.K01 Q liniSS 2002 Exygen Research Exygen Research : 723 : Page 23 of34 Page 206 of 217 MIN 313/023622 : 724 : MIN 313/023622 Exygen Study No 023-076 Exygen MethodNo. ExM-023-071A Rev. 2 FSitgaunrdea3rd. InRjeecptiroenseonftPatOivSeFChromatogram of a 0.01 pg kcsOnd lnVOttaC^/K-oStiM#0uulBMfcVaTaaaiMXMinrn 2XftMnapnltasutafaureaar> M la In fo i Z Al SOOT, lla3L002haad3api Mncap SfU o f aSftg/ofi Bed. IandIM ln sr Acnfet&od a . ISat. v i M al v ia l Huetent i SOS WPW At'a*a"4h7, tii M linr o Exygen Research Exygen Research : 725 : Page 25 of 34 Page 208 of 217 MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071A Rev. 2 FS(1ai0gm0uprjeilLe4.RatRSeepruremse)ntative Chromatogram of a Control ne!i?*!2*StSoCrwSIiiS33*,'"S30a/K01s1`3S',0,010iSe1Va ttw39i,wR8K6n\SP*>7amn"ao*a___oa9_t..d*\_=_'_j_W_vaa.t.hl<end503 Exygen Research Exygen Research : 726 : Page 26 of34 Page 209 of 217 MIN 313/023622 : 727 : MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071A Rev. 2 FS(0ai.g1mugprleRe6at Representative Liver) Chromatogram of a Control AOUpUceqKrumalrntaodnrue i<t,3i\JoMVolm-070i\3im3x)0i\4D5703tfel3inQa\XrcMqMa2eatha.oDd S03 JW tf, I n b h u t e p u a i o j . , f t * j j *, .h . i S - o tnio Control. a j S f t W U v o i V U l M u ter. 9 , to* Exygen Research Exygen Research : 728 : Page 28 o f 34 Page 211 of 217 MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071A Rev. 2 RFiagtuSreer7u.m CRoenptrreosleSnatamtipvleeC(0h.1ropmgaItnojgecratimonooffaPFOoSrtFif)ied Oequlcod. Oparae &L\023-071\SAJ!tTX\0?0203OT\MlU02.n Inaerureeni t 3 Jacu/lM3a0093 1111 ia using tojKatbod (03 suvio taut ear. uo.ti--dop inja*vi*al RInunisber>, SUL o f 330(0/ Std. 100(*1td,raUtriuc,suvaial M i-M l <..U ' w V B n u a ' i W i a ' ata I tia 'Ja'VJa .raa '41j Exygen Research Exygen Research 729 : Page 29 of34 Page 212 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen MethodNo. ExM-023-071A Rev. 2 FRiagtuUreri8n.e CRoneptrroelsSenatmatpilvee(C0.h1rpogmIantjoegcrtaiomn ooffaPOFoSrFti)fied wOmpSaztteaSr!;tIt.*1:\o2/-SfnlJ7sifVlo2#i*sSod7tt1aB*,ua#\o*7.wTn"or*iaf*Bo9B9\K3tfeuaJreHaaot7t.oDaS03 aLm- 1t> ia a.1'ila'M Exygen Research Exygen Research : 730 : Page 30 of 34 Page 213 of 217 MIN 313/023622 Exygen Study No.: 023-076 Exygen MethodNo. ExM-023-071A Rev. 2 FRiagtuLreiv9e.r CRonetprroelsSeanmtaptilvee(0C.1hrpogmIantjoegctriaomn ooffFaOFSoFrt)ified ImtrmoRtMOjwWafScicnad: ilAiSt\<gAacl/lk-3as0T0*i3s\*w B M . iV J 7 0 3 o \tto a a ia . 1*3 pet alog Adptaehod 503 jl g U ?*m* ` sed, u n i -ria l Exygen Research Exygen Research 731 : Page 31 of34 Page 214 of 217 MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-O23-071ARev. 2 RFiagtuSreer1u0m. CRoenptrreosleSnatamtipvleeC(0h.0r1omfigatIongjreacmtioonfoafFPoOrtSifFi)ed M l M 'O p *c *to r - 4 .1 iM4 . UKI UKUMHl a IW*.UWUW..1X IW W,_11 ? A C 4U lxd t 3 J U l 3003 3 i0 9 pm t u in g Jbcdtotbod 803 * QG/M3 X n *tro n t 8ft _ Sm lm ita id ii P C 8 p / iw ti b w d i^ c * In ] . , lt d , U L v ia l Zuio tX ia a 5jiL o f * t d . + IOQkL c a t stxuat v ia l a ia b o ri a #. . B55I55 MO 4000 . ( W ' 9M iMOO SCO 1M 1000 M3 ' l a w &L .'d ttbe'Shii aha ^ " g - a s - H Exygen Research Exygen Research : 732 : Page 32 of34 Page 215 of 217 MIN 313/023622 Exygen Study No.: 023-076 ExygenMethod No. ExM-023-071A Rev. 2 FRiagtuUren1n1e. CRoenptrreosleSnatamtipvlee C(0h.0r1ompgatIongjeracmtioonfoafFPoOrStiFfi)ed VoApIcqu!utiHt*a*ucmbert1'j*3sA*3LdooMeut/i---Mao20nsQ#-\nsa3/MM'-tJD-*i-mtl-dt-\.os-7ori<auorMiino'og.ja\rmei.eqBUMoa'BSi7fIe..meiv>dirSiU CW1HIMJ UHWri. ri, ri.'Wi*"ja a,'iirai m .w z. Exygen Research Exygen Research : 733 : Page 33 of 34 Page 216 of 217 MIN 313/023622 Exygen Study No.: 023-076 ExygenMethodNo. ExM-023-071A Rev. 2 RFiagtuLreiv1e2r.CRoenptrreosleSnatmatpivlee (CQh.0r1omfigatIongjercatmioonfoafFPoOrStiFfi)ed aZcaqautniriMednfc tOperator KvmiiofalvelXHt*nLfnftaaubuerit:t 4s9p30u*JO9ua*CLt/HlufZ2lL0S*Mwh9 *f&mdaZpt&343c*apla+s jv.m<l a g Xutftetbad Stdra, tialinv*e rv i att al i w** S B B 3 S 3 ** ^ jgSQg Exygen Research Exygen Research : 734 : Page 34 o f 34 Page 217 of 217 MIN 313/023622 HUNTINGDON RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2001 THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM GOOD LABORATORYPRACTICE STATEMENT OF COMPLIANCE IN ACCORDANCE WITH DIRECTIVE 88/320 EEC LABORATORY TEST TYPE HHWuuonnottliiennyggRddooonnadLRiefseeSacrciehnCceesntre AHPCEalucm2no8tbnin4sb.gHudrSyon AECclnioansliyycstaitlceCamlhsCemheimstrisytry EEPThonnyxvvsiiic/rrCooolnnhommegmyeennTttaaellstFTinaogtxeicity DATE OF INSPECTION 15thJanuary 2001 Awasgecnaerrrailedinospuetcatitontheforabcoovme pllaiabnocraetowryithasthpearPtrionfcipUlKes GoLfPGCooodmpLlaiabnocreatoPrryogPraramcmticee. At the time of the inspection no deviations were found of sufficient magnitude to affect the validity of non-clinical studies performed at these facilities. V t/ l DHre.aRd,oUgeKr GG.LAPlMexoannditeorring Authority : 735 : MIN 313/023622 HUNTINGDON RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2003 THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM GOOD LABORATORY PRACTICE IN ACCOSRTDAATNEMCEENWTITOHFDCIORMECPLTIIAVNEC8E8/320 EEC LABORATORY TEST TYPE AWHCPHHElauuucom2nnnoo8ntttlbiiilnbnn4esHguygg. dddrRSyoooonnnaLRdiefseeaSrcciehnCceesntre TPEEEAChoncnnlioyxvvnassiiilicyrr/ycCooosattlnniholecmmemCgamylheesCnneTmtthaaeesllimstTFtsriaosytxtericyity : 736 : MIN 313/023622 HUNTINGDON RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2005 : 737 : MIN 313/023622 EYE RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2001 THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM GOOD LABORATORY PRACTICE STATEMENT OF COMPLIANCE IN ACCORDANCE WITH DIRECTIVE 88/320 EEC LABORATORY TEST TYPE HEyuenRtinesgedaornchLCifeenStcrieences SIPu2ff3o7lkPX ACEEEMTPhncnonluioxyvvnatsisiiliacyrr/ycCgooosattelinnhloecnmmCemagimlycheesiCnnteTymhttaaeeillsmstTFtirinaosytgtxeriycity DATE OF INSPECTION 29" January 2001 A general inspection for compliance with the Principles of Good Laboratory Practice was carried out at the above laboratory as part of UK GLP Compliance Programme. At the time of the inspection no deviations were found of sufficient magnitude to affect the validity of non-clinical studies performed at these facilities Dr. Roger G. Alexander Head, UK GLP Monitoring Authority : 738 : MIN 313/023622 EYE RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2003 THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM GOO LABORATORY PRACTICE STATEMENT OF COMPITANO' IN ACCORDANCE WITH DIRECTIVE 88/328 EEC LABORATORY TEST T M HEOycucenoRtlidnesgedaornchLCifeenStcrieences ISPu2ff3o7lkPX AEEEMcnnnuovvatsiilayrrygoostetinncenmmamicleesiCnntytthaaellmTFiaostxteriycity Toxicology Phys/Chem Tests DATE OF INSPECTION 22 April 2003 Awagsecnaerrrailedinospuetcatitonthefoarbcoovme pllaiabnocraetowryithasthpearPtrionfciUplKes GoLf PGCooodmpLlaiabnocraetoPrryogPraramcmticee. At the time of the inspection no deviations were found o f Sufficient magnitude to affect the validity of non-clinical studies performed at these facilities. 2 S j1fo S Dr. R o gers to a a te .Head, IlK.CM Aathority : 739 : MIN 313/023622 EYE RESEARCH CENTRE GLP COMPLIANCE STATEMENT 2005 : 740 :