Document MmzX2mnQQ4QZmK0kDa49RxLa

3M Environmental Laboratory ARG-015T / fz Final Report- Analytical Study Single-Dose Intravenous Pharmacokinetic Study of T-6053 in Rabbits In-Vivo Study Reference Number: HWI#6329-136 Study Number: AMDT-010495.1 Test Substance: FC-99 (T-6053) `Name and Address of Sponsor: 3M SCD Division 367 Grove Street St. Paul, MN 55106 Name and Address of Testing Facility: 3M Environmental Technology &Services 935 Bush Avenue St. Paul, MN 55106 Method Numbers AMDT-M-1-0, and Revisions: Thermal Extraction of Fluoride by Means of a Modified lideAnalyzer-Liver AMDT-M-2-0, Dohrmann DX2000 Organic Ha Fluoride Measurement by Means of an Orion EA940 Expandable - AMDT-M-4-0, Ton Analyzer Extraction of Fluorochemicals from Rabbit Liver AMDT-M-5-0, AElneacltyrsoissporafyRaMbabsist SLpievcetrrnEogxmtterhtaercytSkfaolrarFlSueogrmoechnetmeidcaFllsowUsAinnaglyzer AMDT-M-8-0, Analysis of Fluoride Usi with Ton Selective Electrode Initiation Date: See attachedprotocol . Author: James D. Johnson Approved By: Qon752 ames D, son Study Liretor py: `ompletion Date . ne 03764 000601 3 of 81 (iRnoadnbiebviirtdaublabilivter/radbwobesiertesgrwaoneuarple)y.zdTeodsheebdyfilcnuootrmriabnvueesntwoiauossnldyfeotwreictfthleuadorraiafntneegrceoanostfiesnnigtnlgealtde4od8soesheoosufrosfaFfCte.r99 c2a0lcuugl/aktge,d bwuitthnortesapfetcert a 0.8, to the 4C,81s0oluigd/s.kg dose at 48 hours postdose. Doses are ltToihtvaeelrpoferorrgfaltnouitoacrlofoolrcutgoaarnnieinsecuiflnlfuowonhraoitnleeeswalililtvlefrporarofmtveiordfeiFnaCtr-cao9vn9evndeonouiesesnintnojmetcatcrihkoanen.rgteTohtaehsesaeanvsaasliytlsahibesidloieftrymoafl absorption of FC-99. 0oTch.ti0as4n%esstsuuoldlfyuotwniaaotsneodafensiFioCgn-n9eg9doetssooltpiordost)vhieidsleiavdiemnrifanonirsmdtaoettriheoednriatnsisatsonuewishnetartftahevereranotdhueosspdeeorsofefl;uToa-rn6od0-5t3o (a iasscaerstoaliuntitohneocfhpaenrgfeluionrocaolnkcyelnsturlaftoinoantewsi:thpetrifmleoaufrtoeorcdtaonseesiunlfsoenrautem (anadboluitve2r,0%F)C,-99 aCs4t-heCd7ieptehrfalnuoolraomailnkeylssalutl.fonates (about 5%), and water (75%). The sulfonates are oItctias nkensuolwfnonfarteomansitoundiiess qduoitnee lpornegvi(o>u1slmyonwtiht)h.ratIts,wtahsatsthhoewhnalifn-laifperoevfipoeursflsutourdoy- ithnattratvheenhoaulsf-dloifseeof(pHeWrIf#l6u3o2ro9o-c1t5a9n)e.sulIftoinsantoeties x>p1ecmtoendtthhaitntrhaebbhiatlfs-laiffteerinanrabbits would as it is bceomdpiaffreirnegntFwCi-t9h5ju(sptotthaesssialutm form salt) owfitthheFCp.er9f9l.uorooctanesulfonate changed, tIthewassernuomteldevienlsthleagpgreedviaonuds eivnternadveencoruesassetdudayftewritthhethienjpeecrtfilonuoarnodoctthaennesrueltfuornnaetdettohaa.t maximum at 48 hours. sItulwfaosnactleeawrouflrdomprtohevi2d8e adamyarstkuedryf(orHWdIe#rm6a3l29s-tu1d5i9es) ftohratwthhiecphetrhfelrueorwoaosctraenaes-onable perxopdeucctta.tioItn wtihlalt tpheerrfelfuoorreooacltsaonbeesualfuosneaftuel wmoaurkledrbfeorfotrhemeadssaessasmbeinottroafnstfhoerdmeartimoanl absorption of FC-99. 03765 000002 2 3.1 Tes3t.,1C1onAtnraolly,tiacnald Reference Reference Substances Substance: and Matrices FC-95, lot 161 or 171. They are e3.q1u.i2vaAlneanlt.ytical Reference Matrix: Bovine liver and bovine serum 3.13 3.1.4 AAnnaallyyttiiccaall Control Control Substance: None Matrix: Bovine liver and bovine serum g3r.2ocSeoruyrscteoreo,fbMoavtienreiaslesr:u3m MfrIoCmPS/iPgCmPaDCihveismiiocnalfoCroFmCp-9a5n,ybovine liver from 3.3. Purity and Strength of Reference Substance: Responsibility of Sponsor. 3.4 Stability of Reference Substance: To be determined by Sponsor. 3bi.o5loSgtiocraalgseaCmoplnedsittihoensstofroargeTeisst-2M0at+e1r0iaCl.s: Room temperature for FC-95, For 3G.L6PDiRsepgousliattiioonn offorSptehecitmiemnesp:erBiioodlroegqicuailretdisfsouresstaudnidcsflluoidnsgewriltlhabne retained 28 days. per 4.0 EXPERIMENTAL-Overview wSeerreumavaanildabtlisesufeosr afnraolmysainsimfoarlsflduoosriendeacsodmepsocurnidbsed. (SHinWcIe#6pe3r2f9l-u1o3ro6o)ctanesulfonate asnuibosneqiusennottabniaoltyrsaisnsffoorrmfelduo,ritnhee.anTahlyesifsluwoarisneacdcaotampalriesrheeldatweidtdhirceocmtbluysttoion and pdiefrffelrueonrtotocitmaenienstuelrfvoanlastaeftceorncdeonstirnagtiporno.viTdhees fdlautoariwnheiacnhalcyasnisboefisnteerrupmrectoeldlected at : pahnadr/moarctooktianleotrigcaanlilcy.flTuhoerindeatian alrievetrocparnovbiedeuseevdidtoenacsesetshsatdpeerrmfalluoarbosoocrtpatnieosnuloffonate FC-99. 5D.o1hrAmMaDnTn-MD-X12-000,0 Thermal Organic HEaxltiradcetAinonaolfyFzleru-oLriivdeer by Means ofa Modified E5.x2paAnMdDaTbl-eM-To2n-A0n,alFylzueorride Measurement by Means of an Orion EA940 03766 000003 3 5.3 AMDT-M-4-0, Extraction of Fluorochemicals from Rabbit Liver 5E.l4ecAtMroDsTpr-aMy-M5a-s0s,SpAenacltyrsoimsetorfyRabbit Liver Extract for Fluorochemicals Using 5A.n5alAyMzDeTr-wMit-h8I-o0n,SeAlnecatliyvseisEloefctFrloudoeride Using the Skalar Segmented Flow SODATAANALYSIS~~~ 0000 The data from combustion analysis of liver for total organic fluorine are attached. The liver at 48 hours post dose indicates that only the 250 mg/kg dose of T-6053 resulted in significant total organic fluorine in the liver (35 ug in total liver). This is 0.04% solution of an aqueous solution in which the perfluorooctanesulfonate salt is about 20%. This corresponds to a dose in terms of perfluorooctanesulfonate salt as about 0.02 mg/kg. (The control value is estimated to be about 15 ug total in the whole liver, but the value is below the quantitation limit and is extrapolated from bsteuldoywitnhreabcbailtisbrwathieonn opefrtfhleuoirnosotcrtuamnenets.u)lfoTnhaitse raessutlhteips oatsaesxspieucmtseadltfwraosm a previous injected and only doses above 0.6 in the liver. There is mengo/ukgghroefstuhlteedpeirnfsliugonriofoiccatnatneasmuolufnontasteofprteotsaelntortgaainnidcicfaltueortihnaet if appreciable amounts of FC-99 are absorbed in a dermal absorption study, it will be observed. fOltohweradnaatlayzwearswictolhlieocntesdeluescitnigveelcelcetcrtorsopdreay(smeaesasppsepnedcitcreosm)e.tTrhyiasnddatSak,alaalrthsoeuggmhented supportive, in the opinion of the Study Director is not required to reach the conclusion stated here and therefore is not discussed in detail. 6.1 Circumstances that May Affect the Quality of the Data: The problem with this analysis is that there is too short a time period used for the study. In other studies, it 48 hours. h`aTshebreeednidonb'stearpvpeedatrhatto there is be any aadvlaagntiangseeirnumdocionngcesnetrruamtisonfsorutnhtiisl study, sHiWnIc#e6t3h2e9t-i1m5e9p.eriod was too short and in viewofthe results fromstudy 03767 000001, Tthheeapvaeirlfalbuiolriotyooctfanteotsaullfoorngaatneicsalftlufoorirnme (idniewthhoalneollaimviernea)ftoefr FC-99 does intravenous not change injection: TashseesasnatlhyesdiseromfallivaebrsofroprttiootnaloofrFgCa-n9i9c.fluHoorwineevewirllaplraorvgeirdedoasceownivlelnibeenrteqmuairrkede.r fo 8a.p1proRpariwatDeastpaecainmednsD,ataan:d archives. eRlaecwtrdoantiac, daaptparwoivleldbpermotaoicnotla,inaepdprionvtehde fAinMalDrTeport, 9.1 Protocol and Amendments P9.h1a.r1maPcrooktoicnoeltiacndStFuidnyaloRfeTp-or6t0:53HWiIn #R6ab3b2i9t-s1"3(6Pr"oStioncgollet-yDpoeseTPI8nt0r8a4v.enPoKusfor dosing of animals, tissue collection, etc.) 9.1.2 Analytical protocol AMDT-010495.1 9.2 Signed Reports from Individual Scientists: None 9.3 Quality Assurance Unit Statement: See attached 9.4 Key Personnel Involved in the Study: See attached 9.5 Materials and Equipment: See methods 9.6 Solutions, Reagents, and Standards: See methods 9.7 Sample Preparation: See methods 9.8 Quality Control Practices: See methods 9.9 Test Methods: See Protocol AMDT-010495.1 9.10 Instrument Settings: See methods 03768 000003 5 9.11 Data: See attached. 9ex.t1r1a.c1tiSounmfmoallroyweadndbyraawnadlaytsai;s uusginFg" iOnriwohnolieonlainvearlyazserd.etermined by thermal 9-11.2 Summary and mass spectrometry. raw data; analysis of liver extracts using electrospray e9x1t1r.ac3tiSounmfmoallroyweadndbyraawnadlaytsai;s selective electrode. ug F' using Sinkawlhaorlseeglimveenrtaesddfeltoewrmainnaeldyzbeyr twhietrhmiaoln 03759 000006 "9.S1i.n1glPer-oDtoocsoelIanntrdaFviennaolusRePphoarrtm:acHoWkIi#n6e3ti2c9-S1t3ud6y of T-6053 dosing in of aRnaibmbailtss,"t(isPsruoetoccoollletcytpioen,TPet8c0.)84.PK for 03770 000007  WISCONSIN MOB R AGTs ag0 138 Sponsor: St. Paul,EYMinnesota + CORNINGCaryn, Lange Pp cs hsoy FINAL REPORT Study Title: Single-SDtousdey IonftrTa-v6e0n5o3usinPhRaarbmbaictoskinetic Author: Steven M. Glaza Study Completion Date: March 31, 1995 EerforningLaboratory: H3a3z0l1etoKninsWmiasnconBsoiunl,evaIrndc. Madison, Wisconsin 53704 aboratory Project Identification: HHI 6329-136 03771 EPXhPoRnEeSS-6M0A8I.L241D.E4L4I7V1ERY. Page 1 of 25 3301 KINSMAN BLVO MADISFOoNx. 608.2410.0720207 05 wi anes Page 2 of 25 QUALITY ASSURANCE STATEMENT HHT 6329-136 IfJ{hia7estcs0ornorsSleiolpnnao,dwritnLIganhcba.os,rabteioenrnyacrPcerovaricdetawineccdee bRwyietgthuhleatthQieuoanlFsio,otdy21AansdCsFuRDrrau5ng8c.eA3d5Unnii(n5ti)ooif(r5Hcaze7l)ee.ton esSttnauinddnyadrDidinroegpcsetroaartriieannnsgdpisempscrautoneicadoegndestumorewenHestar..zelectWoornnidtumtcaetnneadgsetamanetdnutsfimrnoednpitonhrgtlssy raoefcpcoorirumdceidpnegcttoiiyiInhce Inspection Dates --fFron _To-- Pha RepoDratteed to Date to 1122//2079//9944 92/15/95 1122//2019//9944 02/15/ se studyDirector Management SParmoptolceolColRleevciteiwon 1122//2079//398% 0o10/11/010//9955 03/30/35 03/30/9955 RDeaptoar/tRepRoerrteviReewview 0032//3105//9955 0043//1100//3955 Reepcrieisieantia.tiDvaen,neQruality Assurance Unit 03772 Date 3a /95 000009 Page 3 of 25 STUDY IDENTIFICATION Single-Dose Study IonftrTa-v6e0n5o3usinPhRaarbmbaictoskinetic HT 6329-136 Test Material Sponsor Sponsor's Representative Study Director Study Location StEuxdpyerTiimmeenttaabll/eIn-Tife Start Date Experinental/In-1ife Termination Date T-6053 MToxicology Service 3MMedCiecnatler,DeBpladrgt.men2t20-2-02 SPt..0.PaBuolx, 33MN22055133-3220 J3MohnToxL.icoBluotgeynhoSfefr,vicPehDMedical 3MDeCepnatretrm,entBldg. 220-2-02 SPt..0. PaBuolx, 3M3N22055133-3220 (612) 733-1962 HSatzelveentonM.WiGslcaoznasin, Inc. MPa.0d.isoBno,x 7545 WI 53707-7545 (608) 241-7292 Hazleton Building NWoi.sc3onsin, Inc. M3a8d0i2soPna,ckWeIrs 5A3v7e0n4ue DDeecceemmbbeerr 27, 29, 11999944 03773 000010 Acute Toxicology SSttuedvyenDiM.recGtloarza Manager SFtruadncyisCoo(rBduid)natW.orMcDonald PIant-rTiicfieaSuPpaedrgvhiasnor RReopsoertH. `SBurpiedrgveisor Quality Assurance MSahneargreyrR. W. Petsel Page 4 of 25 KEY PERSONNEL HNT 6329-136 LaboratoryAnimalMedicine DCiipnldoymaJt.e,CarAyL,AMDVM Supervisor AnatomicalPathology JDeabcokraSherfL.ortP/irkel NSeucpreorpvissyors ASnunpeervMiossohrer Pathology Data 03774 000011 Page 5 of 25 CONTENTS KSQetuyuadlyiPteyrIsdoAensnnsteuilrfainccaetioSntatement OSbujremcatriyve TTReeessgttulSaayntsdotreCymonCtormoplliMaantceerials PrRoecseudltusres SDiisgcnuastsuiroen Table 21 IInnddiivviidduuaall CBloidnyicWaelighStisgns(g) AppPernotdoicxolA Deviations Protocol TPB0B4.PK HHT 6329-136 Page 2 33 76 77 98 111 1 1132 11s 1s 03775 00001: Page 6 of 25 HWI 6329-136 SUMMARY Tahdimsinissttuedryedwasbydoinnetratovenaosussessinjtehcetiloenvelto ofrabsbyisttse.mic exposure of T-6053 when was 0.5 ml/kg for all groups. Female Hra:(NZW)SPF rabbits (one/group). On Day 0, the were assigned at animals received random to fivegroups a single intravenous Tt-h6e05v3e/hkigcloef (bsotdeyriwleeigwhatter(Gfroourpsin1jetchtiroonu)gh o5r, 10r,esp5e0,cti1v2e5l,y)o.r 25T0hemdgionsojefectvioolnumeof Chinical 48 hours observations were after intravenous conducted at approxinately 0.5, 2, 4, 24, and before test material 4 mL) was collected injection. Body administration (Day 0). weights were determined just A blood sample (approximately animals at 2-, 4-, the time of in-1i from an auricular artery or marginal ear 6-, 8-, 12-, and 24-hours post-injection. vein of the In addition, at osfepbalroaotdedwaisntoobsteairfnueendteanrfdmriocnmeatleilaoucnlha(ra4n8if-mrhaaolc.utriosnAslp,losatsn-adimnpjlseeenscttiwoetnro)e,ctehenatpSprprioofnxusigomerad.t,ely 20 mL Asopdpiruomximpaentteolbyar4b8ithaolu,rs blpeodst-viianjetchteiopno,sttehreioranviemnaals cawvear,e anesthetized with and exsanguinated. abbreviated collected. gross necropsy examination The whole liver, bile, and was not done, however, both kidneys from each tissues were animal were An cphoalslee.cted and sent frozen to the Sponsor after termination of the in-life AT five animals appeared normal throughout the study. 03776 0000173 Page 7 of 25 HNT 6329-136 OBJECTIVE ttTohheeratsbebbsjitetcsmt.aitveerioafl,thiTs-60s5t3u,dywhweans atodmiansissetsseretdheaslevaelsinogflesysitnetmriavcerenxnpeosuirnejecttoion REGULATORY COMPLIANCE mfwAidabxnbstionriassttoturrdyaytiSwotaunsd'isceosGn,odoud2c1teLCdaFbRoirna58ta,ocrcwyoirtPdhraantcchteeicweeixtcRheepgttuhileoantUi.oSt.nhsatFofaoondralNayonsndicslDirmuoigfcatlhe u tes dAfnioirnmedacultcrotereWs,de.lftfoarrAeIcToAncpctreoncRteregadutuliraoetnsi,ounshseo.dmogineInnethitihtsey/sosoptliuundbiyiolnwietoryaf, tihanendcoSmpspotnlasiboairnlcieatnyawsiwtiehrudpnyoeee t he study did not unnecessarily duplicate any previous wors. TEST AND CONTROL MATERIALS Identification aL[Tahibceuloiertdae.tsotriTmeahste,erciLoaonlttroNwloa.sma8it6de-er7ni4ta8il-fDiMwe-ad0s2a;SsteETxr-pi6.l0e5M3aWraactnhedrd1,efsorc1r99iI6bn)ej,dectaainsodna,wacslUesadr(e,Acbecbroosltiotyrleass ar, colorless Tiquid. s Purity and Stability sfdItaheatetbeerrSimpaiolnn/asvtoeirhoinacsslseu(mimeniscxlturuderisenpsgonsfuionrbdierlciotntyceestnftorcraotntideoisntt,iomnassto)el.ruibaillAitspyau,mrpihltoeymooagfnednstehtieatbypi.ulitnty mPaetfeureiislatiletdywebarynealtcyhoesnessSipdowenarssoerdn.otto Ttbhaeekeanpduerbqieutfyaotreeandfaodrsmtiatnhbieisltpirutarytpiooosnfest4hseoftUhStihePisgwreassdteauodtcyondtrol Storage and Retention . S3STtfhtateonerdretdecsotrmepfmlraeittgeireoirnaalteodfw.asallAsntyoirneu-dniufsaeetdtretoseotsmitntgmeamtpaeecrrciaoatrludrienw.gas toTrheHetauzrclnoeentdtornotloHimtaohtceeornSispaoolnn(sawHeaHsI otheratredstOipnegratainndgwiPlrlocendoutrebe (dSiOPs)c.ardeAdnyafrteemrainiisnsguanvceehicolfethmeayfibnealysrepfoosr. ) 03777? 000014 Page 8 of 25 Safety Precautions HWI 6329-136 The and test and control policies. material handling procedures were according to HHI SOPs Test Anima TEST SYSTEM AKadlualmtazaolob,inMoicrhaibgbaintsonofNotvheemHbrear: 3(0N,ZW)19S9P4F strain were received from HRP, and maintained at theHazleton Inc., Wisconsin facility at 3802 Packers Avenue, Madison, Wisconsin. Housing Abufrtienrg reaccecilpitm,atitohne aanndimatlhsrouwgehroeutactchleimasttueddy,forthea apneirniaolds owferaet ilenadsitvid7duaalylsy. choonutsreodlliend sqcuraeretne-rbso.ttomEnvsitraoinnmleenstsalsteceolntrcoalgsesfoirn ttheempeanriantaulre-rooanndhweurmeidsiott'y-to m1a2i-nhtoauirn Tia ghtte/m1p2e-rhaotuurredaorfk19lighttoin2g3Cc,yclae.relaItnivceasehsumiwhdeirtey of 50% 20%, and variations from a these conditions adverse effect on existed, they were the study outcome. documented and considered to have had no Animal Diet TLahbeoraantiomarlysRawbebriet prDoievtideHdF #a5c3c2e6s,s PtHoI waFeteedrs,adIn7ci.bitTuhmeanfdeeda miseasrouurteidnealmyo.unt of caonnatlaymziendanbtys.theSammapnluefsactoufrethre fwoartenrutarrietiopnearliodciocmaplolnyentasnalaynzdeednvbiyroHnWmIe.ntaTlhere - were no known contaminants interfered with or affected in the feed the results or water of the at levels study. that would have , Selection of Test Animals wTehree ansiemlaelcstedwerate riadnednotmifibeadsedbyonanihmeaa]lthnumabnderboadnyd wceoirgrhetspornedqiuinrgemeeanrtst.ag and 03778 0000175 Page 9 of 25 StudyDesian PFleamcaelde ainntionaltshewefioglhlionwgingfrsotnud2y,5g7r2outpos:2,836 g Group Treatnent (ngDoTs-e60L5e3v/ekla) 1 (Co2ntrol) T-60*53 100 43 TT--66005533 51250 5 T-6053 250 * Sterile ater for Injection, USP. at initiation Dos_e(nlV/koal)ume 00.55 0055 0s HHT 6329-136 of treatment were ofNuAmnbiemarls 11 11 1 Justification for Species Selection cHhiositcoericbaelclayu,sethoef tNheew lZaeragleandamoWuhnitteofalbbaicnkogrroaubnbditihnafsorbmeaetnionthaenatnhimiasl spoefcies. PROCEDURES Dose Preparation and Adninistration TsrhpeeescpietfceitscitvemcaotnteecrseitnatlrsaowtlaiuostinodniflourotreecdaocnhwtirtdoholseSwtaelserviecllae.icWualtAanetreidnfdoirfvoirIdnuejaaelcchtidooannsiemtaoolfabecaahcsiheedveona aidtsninbiosdtyerweedighbty given as a slow poiunnsthrtahve(eandpoapuyrsoxoifimnajttereceltayitom3en0nti.snetcooTnahdesmarrtegosipn2ea.cl5tiemviaenrutteveessi.tn,isnoldTuuhteiroandtoiswoeany)was Tahdeminpirsetpearreedd. discarded. teAstftesroluatdimoinnsistwrearteiosnt,oreadny artemraoionmintgemtpeesrtatusroelutuinotinls were ReasonforRoute ofAdministration Intravenous injection is an acceptable route to assess systemic exposure. Observations of Animals C48linhiocuarls aofbtseerrvaitnitornasvenwoeurse cionnjdecutcitoend. at approximately 0.5, 2, 4, 26, and 03779 Body weights were determined just before test material administration (Day 0). 000016 Page 10 of 25 Sample Collection HI 6329-136 A blood sample (approximately 4 mL) was catheterization of the auricular artery collected from either ear via the or from the marginal ear vein of all naencirmoaplssy at(a2p,pr4o,xim6,ate8,ly 124,8-haonudrs24pohosutr-sinjpeocstt-iionnj)e,ctaiopnp.r"oximAtatetlhye time of 20 mL ofblood was obtained from the posterior vena cava of stored at room temperature until centrifuged each animal. and separated AT) samples were into serum and cellular maintain fractions. The blood samples were a temperature of -20C 10C until then stored in shipped to the a freezer Sponsor. set to Pathology Aatnimtaelrsminwaetreionaneofsthtehetiziend-lwiiftehphsaosdeium(appepnrtooxbiamrabtietlayl,48b-lheodursvipaostth-eipnojsetcteiroino)r, vena cava, and not conducted, ehoxwseavnegru,inattiesds.uesAnweraebbcroelvlieactteedd.grosTshe nwehcorloepsyTiveexra,minbialtei,onanwdas both ice, kidneys from each animal then placed in a freezer were collected and immediately placed on dry set to maintain a temperature of -20C 10C. After tissue/bile collection, the animals were discarded. Shipment of Tissues After completion of the in-life phase kidneys were sent frozen (on dry ice) the blood samples, livers, bile, and to the Sponsor (James D. Johnson, 3M E.E. & P.C., Bldg. 2-3E-09, 935 Bush Avenue, Sponsor is responsible for the retention and St. Paul, MN, 55106). The disposition of the samples. HWI does not collected in accept any this study responsibility for the analysis nor are these results presented of in the samples this report. Statistical Analyses No statistical analyses were required by the protocol. Location of Raw Data, Records, and Final Report The raw data, records, and an original signed retained in the archives of HWI in accordance copy with of the final HNI SOP. report will be 03780 000017 Page 11 of 25 BodyWeights RESULTS Individual body weights at initiation are in Table 1. HWI 6329-136 Clinical Observations Individual clinical signs are in Table 2. throughout the study. All five animals appeared normal Pathology All animals survived to termination grossly when sacrificed. of the in-life phase and were not examined DISCUSSION The level of rabbits when systemic exposure administered as a of T-6053 was evaluated in female albino single intravenous injection at levels of 0, 10, 50, 125, study following and 250 mg/kg. administration All animals appeared of this material. normal throughout the SIGNATURE EEO SO Steven M. Glaza Study Director Date Acute Toxicology 03781 000015 Grow 1 2 3 4 5 Page 12 of 25 Individual Table Body 1 Weights (g) Dose Level (m/ka) Sex Animal Mumber 0 Female F52856 10 Female F52857 50 Female F52861 125 Female F52862 250 Female F52863 Initial 2,833 2,802 2,572 2,746 2,836 HKI 6329-136 CO3782 000014 Dose Level Grow (ma/ka) 1 0 2 10 3 50 4 125 5 250 Sex Female Female Female Female Female Page 13of25 IndividuTalabClleini2cal Signs Animal Mumber F52856 Observation= Appeared normal F52857 Appeared normal F52861 Appeared normal F52862 Appeared normal F52863 Appeared normal HWI 6329-136 Hour. 05 2 4 uw SAS yy Sry SL ry Soy SL vy / Condition existed. 03783 000020 Page 14 of 25 APPENDIX A Protocol Deviations Protocol TP8084.PK HMI 6329-136 03784 000021 Page 15 of 25 Protocol Deviations HHI 6329-136 ---- Protocol CP.agDeo8s,ing7. PrEoxcpeedruirmeesn,tal(1)Design, DionsjiencgtioRnoutien.to aInmtarragviennaolusear 6v0einsecoovnedrs.approximately 30 to ---- ActualProcedure AFn5i2n8a6l1 N(oGsr.oupF532)8,56an(dGroFu5p28612), d(uGrraotuipon4),ofha15d7,a'd91o,sinagnd 99 seconds,respectively. Tohuetcsoemedevofiattihoensstuadrye. not considered to have had an adverse effect on the 03785 00002 @Hnzietoy ) PMOASBTISOONFFWIiCE 51ROfaXy 755044s% Page 16 of 25 +CORNING Corus Sponsor: St. Paul,ElMinnesota PROTOCOL TP80B4PK. Study Title: Single-Dose IonftrTa-v6e0n5o3usinPhRaarbmbaictoskinetic Study ) Date: Decenber 13, 1994 Performing Laboratory: - Ha33z0l1etoKninsWmiasnconBsoiunl,evaIrndc. Madison, Wisconsin 53704 aboratory Profect Identification: HAI 6329-136 93786 PEXhPoRnEeSS nMoAsIL241DEaLsIsVERY 3001 KINSMAN BLVD maoiFsooxn 60w8i.|241si1l2l2s, 000023 Page 17 of 25 ) PPa8g0e84.2 pK STUDY IDENTIFICATION Single-Dose IonftrTa-v6e0n5o3usinPhRaarbmbaictoskinetic Study HN No. 6329-136 Test Material T-6053 Sponsor 3MDeTpoaxritcmoelnotgy Service Medical 3P.M0.CenBtoxer,332B2ld0g. 220-2-02 St. Paul, WN 55133-3220 Sponsors Representative J3oHhnToLx.icoBluotgeynhoSfefr,vicPehDMedical 3HDCeepnatretrn,entBldg. 220-2-02 ) SPt..0.PaBuolx, 3H3N22055133-3220 (612) 733-1962 Study Director HSatzelveetnonH.WiGslcaoznasin, Inc. MPa.0d.isoBno,x W7I54553707-7545 (608) 241-7292 Study Location HBauzilleditnogn WHoi.sco3nsin, Inc. M3a8d0i2soPna,ckeWIrs A5v3e7n04ue PrEoxppoesreidneSnttuadly STtiamrettaDbaltee Experimental Termination Date DDeecceemnbbeerr 2297,, 11999944 Draft Report Date February 2, 1995 CO3787 000023 Page 18 of 25 ) PTa8g0e843. pK 1. SSitnugyle-Dose Intravenous Pharmacokinetic Study in Rabbits 2. PTaduomrsipsnoisesestseretdheaslevaelsinogflesysitnetmriacveneoxupsosuirnejecwthieonntthye rteesptcimraterial 1s 3. Re[LexhaacibuesolpratastittooounrrdyyyCthwPoairmtlap]cltaiinbcaaeelnyccsRoeinesdguocuftletadhteiintoeansctsco,mr/adtaSentrciaeGanluwdiiatdherfdtnhsee,s fwoiltlnowitnhge Gaod ccoonndcuecntterda:tion, solubility, haogeneity, and smtiaxbtiulristsy wriot] not be [[X1] C21onCdFuRct58as(FaDAN)onregulated Study [[[1] 11 4400 CCFFRR 716902" ((EPPAA--TFSiCFAR)) C(81)30 (Final) (ocd) [[1] N5o9tiNfoihscaantioHno.No3.850313(Ja(pJaanpeasneeseMAFMFo)I) ) wMd{oie1rr1lkef.captrroeorc,AecdtuthreeRsegsutilunadtytihodinosse.sprontoIotncoutlnhneeacorepesisniainroincloymopfdluitpahlenicceSaptwoeintsahonrytahpnedrAensivemuiasals 4. QtT(huhNeaeIl)ipQrutoaSytltoiaActnsoydslau,ArrdsasnsuOctpreueadrnyactecionnUgdnuictPtr,ofcneadanucdrceotshredanFcienalwitrhepoHratzlewtiolnl Wbeysauedoittceed by (SoPs) and pol eins. 5. Test Materia A. TId6e0n8t3ification B. Ph(yTosibcealdDoceusncernitpedtiionn the raw data) C. hdP fToeehmsetoteu grSemmpnaioaetnnr nieastrdtoyiirS,i aotlnaas/sbvst ieu(lhmiiientcsy clyl.eurdemisinpxgotnuusrniedb(eisrl)ittyefsotrfocrcoonnpcdueirntititroyantsai)no.dn,s"tSsaaobmjipullpieirt1yoitfy, ttaaedkrmeminin)niastwtiirloalntiobfeonarndsipefnostsrtseaiqtbbouilelestithteeaydnaSalpbnyoyasnlisytsohs.reesaSpfwotinlelsroerbx.opetrTahkieemnseentbses)faomrpeles (if 03788 000025 Page 19 of 25 ) D. SRtooomragteemperature PPa8g0e844. pK E. ReserveSamples Reserve samples will not be required for this study. F. Retention cAonmypluentuisoend otfestthematienr-ilailfewiplhlasebeofretthuerne`sdtutdyo. the Sponsor after 6. SafetyPrecautions 6. ContrAosl rMeaqtueirrieadl by HWI SOPs and policies A. SItdeernitliefiwcaatteironfor injection B. PhysicalDescription Clear, colorless liquid C. PuarndSitabtiliyty ) The purity considered and stability of this usp grade to be adequate for the purposes material is of this study. D. Storage Refrigerated E. ReserveSamples See Section, 5. E. ReserveSamples F. Retention . Any and wrielmlainnoitngbecondtirsoclardmeadteraifatler maiyssubaencuesedof ftohre otfihnearltersetpiorntg. 6. Safety Precautions As required by HNI SOPs and policies 7. Experimental Desian A. Animals . (1) Species : Rabbit (2) HrStar:a(iNnZ/No)uSPrEc/eHRP, Inc. ) (3) AAdgueltat Initiation 03789 00002 ) ) ) Page 20 of 25 (4) Weight at Initi ation 2.5t03.5kg PTaPg8e0584P.K (5) NumberandSex 5 females (6) Identification Individual numbered ear tag (7) Husbandry (6) Food (a) Housing Individually, (heavy gauge) in screen-bottom stainless steel cages A(PmHIeasFeuerdesd, amIoncu.n)t. ofThLeaboforoadtoriys RraobubtiitnelDyietanHaFly#z5e3d26by the manufacturer for nutritional environmental contaminants. components and e) Environment (c) Mater Ad Tibitum from an water are analyzed automatic system. Samples by HWI for total dissolved of the solids, hardness, and specified microbiological for selected elements, heavy metals, content and organophosphates, and chlorinated hydrocarbons. (d) Contaminants There are no known contaminants in the that would interfere with this study. food or water Environmental controls for the animal set to maintain a temperature of 19C room will be to 23C, a r1eilgahtti/v1e2-hhouumrididtayrkocfyc5l0e%.420%, and a 12-hour (f) i (8) SeleofcTetstiAnoimanls nBaoadseaeqnduiamtoaenl nhueimnableotrhbvioaofnudselxbytordapyoowarneiimhgaehlatsl.tahwcicloilsrdibpenlgacpeutdorcohHnaIsetedSsOtPs.so. thAant Htbhaiecsktgoarrnoii1mucanaldllA yoi,fnfcothhrehmoeaitcNieeow2n0b)ZeoecnaalusatenhdisofWshpit!ethceeiealsal.rbgii enoamroaubbbnibttitofhas has bebeen 03790 000027 Page 21 of 25 7 8. DoAsdeministration (1) Test Groups PTaPg8e0684P.K Group 1 2 3 4 5 DoosaeLke)vel 0 (Control) 10 50 125 250 NEuemnbaelresof 1 1 1 1 3 a The dose weight. volume will be 0.5 mL/kg of body C. DosingProcedures (1) DosingRoute aIpnptrroaxviemnaotueslyin3j0ecttioon60 isnetcoonadsm.arginal ear vein over (2) RefoarDossinog Ronute ) sIynsttreamviecnoeuxspoisnujreec.tion is an acceptable route to assess (3) Dosing uration Single dose (4) DPosreeparation The test material will injection to achieve a bsepecdiifliuctecdonwcietnhtrsatteiroinle fwoarteerachfor dose level. the animal's bIonddyivwiediuaglht dotsaeksenwJiullst bebefcoarlecutleasttedmabtaesreidalon aatdmrionoismtrtaetmipoenr.atur"Teheunptrielpaardemdintiessttramtiixotnu.res will be stored D. O(1)bsCleinricvao)afOAtbnsiiemroavalntsions The animals after treatment. toxicity at awiplplrobxeimaotbesleyrve0.d5,fo2r.0c,lin4i.c0,al 24s,igannsd o4f8 hours (2) Body Weights Just before test material administration. (3) samsleCollections 03791 ) (a) 2Fr,e4q,ue6n,cy8, 12, 24, and 48 hours post-injection 000025 Page 22 of 25 y PPa8ge0874P.K (6) aMnunofbAneimarls () Meotf Cholloectdion fBrloomodeistahmeprlesear(avpiparotxhiemactaetlhyet4ermiL)zatwiiolln be collected of the auricular artery 4, 6, 8, 12, and or 24 from the marginal ear hours post-injection. vein at 2, Approximately documented in t2h0emLrawofdabtlao)odwi(lalctubael obvtoaliunmeed tforbome the posterior necropsy vena cava of each animal (48 hours post-injection). at the time of Approximately 20 mL of blood animals during will be collected from moribund the study, also, if possible. The samples will centrifuged, baend stthoeredsepaatrartoeomsetreummpearnadtucreellaunldarthen tfermapcetrioantsurestoofred-20inC a$1f0reCe.zerThseetsetopamraaitnedtaisneruam and Samples will be shipped to: tcheellSulpaornsofrraactfitoenrsexwpilelrimbeentsaelntterfmriozneantioonn.dry ice to ) 3JMameEs.E.D. &JoP.hCn.son Bldg. 2-3-09 935 Bush Avenue St. Paul, MN 55106 James D. Johnson or his alternate telephone at (612) 778-5294 prior will be notified by to the shipment of the samples. E. Termination (1) Unscheduled Sacrifices and Deaths Any animal dying during the moribund condition, will be study or sacrificed in a subjected to an abbreviated argerncoeossrstdheendte.iczreodApnswiyimtaehlxsamsioinndaituaimmonopreinabtnuodbnadarlblciotnaadblintoir(omvniaaliwitilinlejsecbtweiiolnl the marginal ear'vein), bled via be in exsanguinated. Tissues, as descritbheedveinnasceacvtai,on aEn.d Termination, (3) Sample Collection, will be collected. 03792 000029 Page 23 of 25 ) TP8084PK.. Page 8 (2) Scheduled Sacrifice At approximately 48 hours post-injection, animals surviving to pentobarbital termination will (via injection be anesthetized with sodium in the marginal ear vein), gbrloesdsvnieacrtohepsyveneaxamcaivnaa,tioanndwielxlsannogtuinbaeteddo.ne, Ahnowaebvberre,viated tissues will be collected. () Same Collection sTthuedyw,holseacrTiifviecredandinbailmeorfirboumndeacchondaintiimaoln, dyoirngsudruvriivnigng tthoe termination will be collected. animal will also be collected. Both kidneys from each The tissues will beplaced on dry ice immediately after collection and then placed in a freezer set to maintain a temperature of -20C $10C. The dry tissues (liver, bile, kidneys) will be sent frozen ice to the Sponsor after experimental termination. on The samples will be shipped to the person listed in Section 7.D.(3).(c). The Sponsor is responsible for the retention and disposition of the samples. F. Statistical Analyses ) No statistical analyses are required. 8. Report A final report including those items listed below will be submitted. DDeessccrriippttiioonn ooff tthhee tteesstt sanydstceomntrol materials Procedures DDaetsecsripotfioenxpeorfimaennytatloxiicnietfifaetcitosn and termination GGrroossss ppaatthhoollooggyy rfeipnodritngs(if(iafpapplpilciacbalbelea)nd requested by the Study Director) 03793 000030 Page 24 of 25 PPa8ge0894P.K ) 9. OLfroaiccgaiitlniiaotlnatedoaftaauR,daiwtoirDantgcao,ptiheeRsecsottruhddesyr.eodfua,rnidnwgiFlilniatlsbepRreaopvgaorireltsasbleandatbeHfHIoreto 2ra1ec1tcaeipontreaidgnicneianlotfhpeatpheearrcfhdiinavatleas, roeifpnocrHltWu.IdinagWchceotrnhdoistnehgeittfoeinmHaNllIisrSteOepPdo.rtbelioswcwoimlplletbeed, DPorsoetocporlepaarndatipornotorceoclordasmendments InB-o1diyfeweriegchotrsds DOobsseervaadtmiionnisstration SShaimpppliengcorlelceocrtdison records SPtautdhyolcoogryreRsepcoonrddsence Final report (original signed copy) Tnhoet bfeolalrocwhiinvgedsuwpiptohrtitnhge rsteucdoyrdsdatwai.ll be retained at HWI but will ) AWnaitmearlanraelcyesiips't/arceccolridmsation records Animal roon temperature and humidity records RIenfsrtirgumeernattorcalainbdraftrieoenzearndtemmapienrtaetnuarnecerecroercdosrds 03794 000031 Page 25 of 25 ) TPPa8g0e841.0PK PROTOCOL APPROVAL Pom 2 Bitiditf John L. Butenhoff, PhD Sponsor's Representative 3M Toxicology Service Medical Department 2s5 54 Date hI WN, : Steven M. Glaza Study Director Acute Toxicology ) Hazleton Wisconsin, Inc. Date -- Representat{vy Quality Assupance Unit Hazleton Wisconsin, Inc. (6329-136.protdsk2) 12.13.94 Date 03795 J) 00001: 9.1.2 Analytical protocol AMDT-010495.1 03796 000033 3M EnvironmentalLaboratory Protocol - Analytical Study Single-Dose Intravenous Pharmacokinetic Study of T-6053 in Rabbits In-Vivo Study Reference Number: HWI#6329-136 Study Number: Test Substance: AMDT-010495.1 FC-99 (T-6053) Name and Address of Sponsor: 3M SCD Division 367 Grove Street St. Paul, MN 55106 Name and Address of Testing Facility: 3M 935 Environmental Bush Avenue Technology and Services St. Paul, MN 55106 Proposed Proposed CInoimtpilateitoinoDnatDea:te:JulAyug25u,st19259,5 1995 Method Numbers AMDT-M-1-0, and Revisions: Thermal Extraction of Fluoride by Means of a Modified AMDT-M-2-0, FDlouhorrimdaenMneDaXsu2r0e0m0enOtrgbayniMceaHnalsiodfe Analyzer-Liver an Orion EA940 Expandable AMDT-M~4-0, Ion Analyzer Extraction of Fluorochemicals from Rabbit Liver AMDT-M-5-0, Analysis of Rabbit Liver Extract for Fluorochmicals Using AMDT-M-8-0, AEnlaelctyrsoissporafyFlMuaosrsidSepUescitnrogmtehterySkalar with Ton Selective Electrode Segmented Flow Analyzer Author: James D. Johnson Approved By: mes D. JGnson Study Difctor tpofos Date lin XL Budell John Butenhoff, PhD Sponsor Representative ups, Date 03797 000033 1 iTnotraasvseenssoutsheinljeevcetlioonftsoysratbebmiitcs.exposure when T-6053 is administered as asingle `This study is designed to provide information as to whether the `pmeartfelruiaolroioscatdamniensiusltfoenraetdeinanainonindtoreasvegnooutso dtohseeraabnbdittoliavsecreartnadinotthheercthiassnugees iwnhenthe concentration with time after dose in serum and liver. 2.1 Test, Control, and Reference Substances and Matrices e2.q1u.i1vaAlennatl,ytical Reference Substance: FC-95, lot 161 or 171. They are 2.1.2 Analytical Reference Matrix: Bovine liver and bovine serum 2.1.3 Analytical Control Substance: None 2.1.4 Analytical Control Matrix: Bovine liver and bovine serum l2i.v2erS),ouSricgemaofCMhaetmeirciaallsC:o3mMpaInCyP(/2P.C1.P2,Di2v.i1s.4iosner(2u.m1).1), grocery store (2.1.2, 2.1.4 2.3 Number of Test and Control Samples: Liver and serum from 4 test animals baendav1aicloanbtlreolfoarniamnaall.ysiOstihfedrebeimoleodgiacpaplrotpisrsiuaetse (kidney, bile, by the Study cellular fraction) Director. will 2.4 Identification of Test and Control Samples: The samples are identified using nthuembHeWr,Ipalnuismtahle itdiesnstuiefiicdaetnitointynuanmdbedraywhiidecnhtictoyns(issetrsumo)f.a letter and fivedigit 2.5 Purity and Strength of Reference Substance: To be determined by Sponsor. 2.6 Stability of Reference Substance: To be determined by Sponsor. 2.7 Storage Conditions for Test Materials: Room temperature(2.1.1), 20 10C (2.1.2, 2.1.4). Test and Control samples will be received according to AMDT-S-10-0. 2.8 Disposition of Specimens: Biological tissues and fluids will be retained per GLP study Regulation for the is in parallel with time a 28 dpaeyridoedrrmeaqluiarbesdorfpotriosntusdtieusdylosnogaelrl than 28 tissues days. will be This retained. -- 03798 000035 2 a2t.t9irSe.afeUtsye Pcraeuctaiountiwohnes:n RheafnedrlitnogakpnpirvoepsrifaotrecMutStDinSg.theWesaamrpalpepsr,opriate laboratory aaTnnhaaellyyttsiiiscssaulfeostrefsftrlsouocmraiannnebiemcaoplmesprofduoonrsdmesed.d".asATdtehsetchresicdbrieesdecnr(ieHntWgiIofn#o6ro3ff2lt9uh-oe1riS3dt6eu)di,nyalrDieivreaervcatvioilraa,cbaloemsbefuroisretsioofn ff(llSuueooerriiMnneeethcionondttshe-en-tlniewvixerlt.l SbeSecitnaicnoena)pcecirusfrtlahuteoeraoepsoptcritomapanrteiesaoutlfeftoahnneaaltcyesoainsncietnootnprirasetsineoonnttobdfieotftihrneainctsiovfmeoprdomauetnda,df.or 4.1 Liver and Serum screening methods: (attached) D4.o1h.1rmAaMnDnTD-XM2-010-00,OrTghaenrimcaHlaElxitdreacAtniaolnyzoefrF-lLuiovreirde by Means oaf Modified E4x.p1a2ndAaMbDlTe-TMo-n2A-n0al,yFzleuroride Measurement by Means of an Orion EA940 4.1.3 AMDT-M-4-0, ExtractionofFluorochemicals from Rabbit Liver U4.s1i.n4gAEMlDecTt-roMs-p5ra-y0M,aAsnsalSypseicstroofmReatbrbyit Liver Extract for Fluorochmicals A4.n1a.l5yzAeMrDwTi-tMh-I8o-n0S,eleAcntaivleysEilseocftrFoldueoride Using the Skalar Segmented f5l.u1orDiadteapeRreptoirsstuiengo:r flDuaitd,aowrilalsbFeCr-e9p5or(teeldecatsroaspcroanycemnatsrastsiponec(twreoimgehttr/yw)epieghrtu)niotfof rteisgsrueessoironflaunida.lysSitsatoisftsicesruusmedc,onactetnhteradtiisocnrsetwiiotnhotfitmheeaSntdudayveDriargeecstoarn,dmsatyanidnacrldude sdteavtiisattiicoanlstoefsctosnscuecnhtrasattihoenSstufdoerndti'fsfterteenstt dmoasye bgreoaupppsl.ieIdftnoecdeestsearrmyi,nseismtpaltiestical difference. 03799 000036 3 6.1 Raw approved Data final and Records: Raw report, and electronic data, data approved protocol, will be maintained ianpptrhoepAriMatDe Tspaerccihmievness., 7.1 AMDT-$-10-0, Sample Tracking System D8.o1hArMmaDnTn-MD-X12-000,0 Thermal Organic HEaxltriadcetAionnaloyfzeFrl-uLoriivdeer by Means of a Modified E8.x2paAnMdDaTbl-eM-Io2n-A0n,alFylzuoerride Measurement by Means of an Orion EA940 8.3 AMDT-M-4-0, Extraction of Fluorochemicals from Rabbit Liver E8.l4ecAtrMoDsTp-rMay.-M5a-s0s,SpAencatlyrsoimsetorfyRabbit Liver Extract for Fluorochmicals Using w8.i5thAIMoDnTS-eMle-c8t-iv0e,ElAencatlryosdiesofFluoride Using the Skalar Segmented Flow Analyzer 03800 000037 3M EnvironmentalLaboratory Method Thermal Extraction ofOFrlguaonriicdeHablyidMeeaAnnasloyzfearM-odLiivfeired Dohrmann DX2000 Method Identification Number: AMDT-M-1 Revision Number: 0 Adoption Date: /o- f-1 Revision Date: None -_-- Author: Rich Youngblom Approved by: le foup Le finn /fof3/7< `Date Litt Jt Quality Assurance fos2-4-7 Date Software: MS Word 5.1a Affected Documents: AMDTE-xMp-an2daFbllueorfiodneAMneaalsyuzrerement by Means of an Orion EA940 AMDT-EP-3 Organic RHoaultiidneeAnMaaliynzteernance ofa Modified Dohrmann DX2000 03501 ' 000035 wfBilituohSraicdnoepoefn:rosTmehlivesacrtmiievoetushelomedacttrirsiocdfeeos.r.thTehoepefrlautoiriodneoisaftyDpiochalmlay nconllDecXt2ed00in0Tw1h4e0n5.itsiosluutsieodn tfoeorxtarnaalcytsis 11.23 Mpaptlriicceasb:leBiCoolomgpiocaulntdisss:uesF,lupaorrtoicchuelamrilcyallisveorr. other fluorinated compounds, 2.0 KEYWORDS 2DX32F0l0u0or,idfel,uofrloucorhienmei,caexltsr.action, pyrolysis, ionization, ion selective electrode, Dohrmann, halide, 3.0 PRECAUTIONS 3.1 3.2 3:3 PGGrlleaassssssuwwraairrzeeediasgnafdsreaegsxi,hlepa,ruosbtpreogrkaescenosmgpclraasenssbsmeeadeyxgtcaraseuhmsaeenlidynijhiuonrtg.iepsractices required. e33q::u54iPSpoomtleevnnettn.italbbaisoehdazsaarmdpsledsuemtaoythfelabshi,olmogaiycanlemeadtrtioceasl.loUwstehaepmprtoopdrriystdeopwenrsboenfaoprreostteacrttiivneg run, 4.0 SUPPLIES AND MATERIALS +44312 QCCuooammrpptrrzeegsslssaeesdds sHOeaxlmyipgulemen,,boHHaiytgdhwrioPtcuhariTrtbeyofGnlrofanrdeTMee,,trurebeiggnuugll,aattDeeoddhttroom34a05nPnPSSII8..90-097 or equi 444.:564 SOQaruimaorptnlze9g4cl0oal9sl9se9cctoTimoobnuulvsitaIlioson,niHctDSuPbterE,e,nRgetlhiaAndcjeusGtlmasesntGB-u9f4f0e5r-(0T1I2SoArBeq1u1i)voalreenqtu.ivavlaelnetn.t. 44..87 PMoillylsity-rQeTMnewaptieperttes 44..190AHcatmivialtteodnCShyarriconagle,oEr.eqMueirvcalken2t0.05 or equivalent. 4.11 Miscellaneous laboratory glassware 1 5.2 IRoBsMemcoomupnattiDbolher3m8a6nnorD4X3260c0o0mpOurtgearn,ic Halide Analyzer, modified for fluoride extraction. 5$.:43 EDxXc2el00S0prseoafdtswhaereet,, vveerrssiioonn 15..000,ormgordeiaftieerd for fluoride extraction. 6.0 INTERFERENCES m&a1ySvaamrpylferosmizemaitsrliixmittoemdattroiax.pproximately 150 me, depending on sample moisture content, This 03802 : 2 00003. 9 1.0 SAMPLE HANDLING s7-a1mpSlaem.plUesseaftoerncoetps0orbeprhoabnedlteodtrwaintshfebratriesshuaensd.s. Fluoride may leach from the skin to the cm7le-et2ahSnaansmocplal,lpeoesrlomfaentldhivacenurotatlri-enwgacbtuoetarrfdsr.oolmuTtfhireoonzceaufntttleiirnvgeearbcaohanrdldipvalenarcdiessdccuati.lnpaeltasrheoduladndbelacbleelaendedwewiigthh bwoaatte,r,Use a 8.0 CALIBRATION AND STANDARDIZATION 8.1 Preparation of Calibration Standards $1.1 Refer Ttho eprsottaoncdoalrdfsorrtehqautiprreodjefcotr.each project wil need to be appropriate for that individual project. 88..11.32 TFyoprircaablbliyt 5li0v-e5r0s0tupdipems,FuCs-eb9e5eifnlimveetrhaansotlhestmaatnrdiaxr.ds 150 mg) and weigh it in a labeledand tared weigh boat, are Cut used. a piece of frozen beef liver (100 - 8.2 Calibration - Overview Tcuhrevenoirsmraelquciarleidbrtahteiponroicsetdhuereflluiosrtieddebceulrovwe i(sAuMsDeTd.-M-2). However, ifan optional spiked liver 88a..n22d..21cToyAmpbicucasaltlilibynr,agtttihohrneeecmururesvpielnicgfaotrtehtsehoesfaDemXae2cmh0e0stt0haonisddagsreadnneardnadmtaeftdirvbiexyctosynpcpieeknatisrnagtthsieaonmsspalmoepfslsetwsainttdhoabkrednsotewwsintlelds.tbaendards spiked. R8.e2c.o3veSrteadndFar(dugc)uornvethweilyl-abxeisp.lotGteendearsaMtaaessreSgrpeiskseidonFc(uurgv)eoanndthcealxc-ualxaitseatnhde eSqtuaantdiaorndfMoarstshe line 8a2nd.4thMears2svaSlpuiek".eFdCF-95(uigs)6=0.(0A4m%oFutnhtersepfikoerdei0n.m60L0)4 xis(tCheonfca.ctoofr ustsaenddtaordcoinnvperptmF)Cx-9(50.t6o0F04) 8:25 Standard Mass Recovered F (ug) = (TISAB volume in mL) x (Orion reading in ppm) 8.3 Calibration - Procedure $b8e33.1u1.se1dSitRfaurtnthe2Upporrevmiooruse sCalmepalnesCyccolnetsaiwnheednhisgtahrtcionngceinntsrtartuimoennstocfacflhuodraiyd.e. More clean cycles may 888333.222..12BlFPaornerkprasarbebistasmtpuldieesu,siunsgebteheefslaimveermaesththoedsmaatrnidx.typPereopfarmaetartixleaasstt3hesatemsptlseasmpolfeb.eefliver a8(n31a.0l20y.z-3e1Ps5ua0tmmpsglae)mfapoclrcebolirnadniDknosgh.trommaentnhobdoatA.MDCoTm-bMu-s2t efaocrhthseaimopnlesealsecdteisvcereilbeecdtriondseeacntailoynsi9s..0 and 03503 3 0000350 Jb$ue3dfog2ree4mepnrFtoocroerfeadbtihbneigtopwseitrutadhtieotsrh,etcthaheleirbmereaadttieionrng.riesaBsdtuianmbglesfawomiarptlhbelrsaesnupnkteicsltatmthopilsheilsitsmohirotiucilasldrrebeaeacdh0ei.dn0,g3sop(rppumrnetvoiliroilunoswh4ea6r hours). b8e.f3o2re5prFoocreneodni-nrgabwbiitth stthuedicaelsi,btrhaetibonl.ank readings should reach a predetermined fon concentration c8o3m.b2u.s6tiIonm.ay be necessary to mix approximately 50 mg of charcoal with the sample o aid l88a33b.e33l.e1dSwtWeaeinigdghahrbdooautCtsua.trvFleeoarstra1b5bimtatsrtiudxiessa,mpwleeisgh(51s0t0a-n1d5a0rdmsgwbiethe3lrievpelricsaatmepslcesa.chReinctoarrdedwaenidghs in 8st3u.d3y2dataP.lacSetowreeitghheemdabtreiexfsliavmeprlseasmopnlderiyniDcoehorrmiacnenpascakmspltoekbeoetp.them frozen until used. oQ8ru.a3in3nt.ti3hteyboSfetaterhftlewivisettrha.ntdhaerldoowensotrsitnantdhaermdatcroinxc.entFroartiroanb.bitUssitundgieas,Hausmeil4tuoLn soyfrsintgaen,daerjdeacantdfeijxeecdtit on m8a3y3.b4e uAsteldeaatst3therdeipslcirceatteisonshofotuhled banealuyssetd. for the lowest standard concentration; more replicates r88e33p..l3i3c..a65teRsC,uonrmaubnlulasnt1oStthhseterasnsdaaamrmpdplsle.eaf[sofrdoetnshecatrriesbptelaidncdiaantreds.eisctIsiniodgninci9af.3tiecaainnntlddyaadtniaftlfhyearzteenttahcefcrnooermwditrnhegepltoiotchaAetMreDtrTewp-olMa.ce2s.the l8oe.la3ds.tr3e.0p7.l9i5Wc,ahtceeonnasnauldllttshwtaiattnthdhaesrundpseerwhvairvseeoplrbi.ecaetnerwuinl,lcbaelcuusleadtetothcealrc2u.lart2emtuhesrtebgereastsiloenasctu0rv.e9.5. Ifit s not at c8h3a.n3g.e8d.ANneeww ssttaannddaarrdd ccuurrvvee mshaoyuladlsboebreurnuwnhatenthtehdeicscormebtuisotnioofnthteubaenaolryssta.mple matrix is 8.4 Storage Conditions for Standards T8y.p4.i1caSltloyr,asgteanrdeaqrudisreamreensttsorfeodrasttraondoamrdtseamrpeerdaetpuernedeinntploansttihcesicnrdeiwvitdoupalbostttlaensd.ards used. 8.4.2 New FC-95 standards should be prepared at least once a month. 9.0 PROCEDURES 99..11.1TyCpoimcbaulsOtpieornattuibnegtCemopnedriattiuornes:= 950C. 99..11..32 VOaxpyogreiznatainodn/HDerlyiiunmg ftliomwe == 52040ccs/emcionnidtse.. 9.1.4 Bake time = 300 seconds. 99.22.1StIafrttheUpprPorgorcaemduisreno:t 9.2.2 Open the SYSTEM SstEarTtUedP, swtiarntdtohwe.EOX program on the PC. 99.:22..43 PCultostehethfeumSaYceSTmoEdMulSeEaTnUdPthweicnedllowi.n the READY mode. 03804 + 000031 9:25 found When in the tCheEoLvLenChHaEs CreKacmheendut.he READY temperature, run the CLEAN BOATprogram 9.2.6 See AMDT-EP-3 for detaoiftlhse Dohrmann software. m99:.i33x.1SaapOmpprpeolnxeitmEhaxettSerlaAycMt5iP0oLnmEgPorHofcAecThdaCurrHceo:aalndwiptlhactehethseamspalmeplteo aiindtcheomBbOusAtTi.on.It Imfahyisb1esndeocnessary to s9.h3o.u2ldCallossoebeSAmiMxPeLd Ein HwhAiTleCHes.tablishing the baseline and when generating the standineg, ahorpal cuss. l29.a:0b3em3leLdAdsofadm1ap:p1lpeTrocIpoSrlAlieBact:teMivoinollvliuiaml-.eQoTMTfywpTaitIceaSrlAlmByix0st.ou6lrumet.iLontoor151:m1 LTIaSrAeBu:sMedi.lliF-oQrPrTMabwbaittesrtumdiixest,urveeeto1a.0 or 99i.n33c..h45es.RPluGanacsetehtseherEevOliXeala-s5Se0dOtdLhuaIrtDitnShgepptryiorpogolrfyatsmhisefmoCuuOsnMtd BbinuUbtSbhleTeIRtOUhrNNouTmgUehnBtuhE,e iTsIiSnAtBh,e TISAB at least 0.25 099:3t3-h76eITWfIhuSnedAniBltuhtteoeEdmaOTkIXeSpA1r:Bo1gwTraIasSmAuiBss:efMdiintlioslchieo-dl,lQeTMrc,etmtohveesatmhpelceo,llaedcdtiaonn eviqaulalfrvoomlutmheecoofmMbiulsltiio-nQTMbewa,ter r9e3m8ovReinasneytThIeSeAndBorfetmhaeincionmgbuosnttihoenttuubeb.e with Milli-QTM water and wipe with a KIMWIPE to b9io3tt.ht9aomOcwpoitettnhontahtseippsapateumdlpaalpoeprlhioacttahctehorrasonirdmivrlaaecrmuoduevmveiecaden.oyutAr.edmIratoimpnaionyfgMbaeislnhelfciers-osmQartwhyaettboeorastc.mraapAypsabhretciaacdnldesbeedofrtfoetmhtoeheved 9b.o3a.t1t0o aCildosien tthheeChlatecahn.Cycle. 93.11 93.12 SRaumnplteheisCrLeEadAyNfoBr OanAalTyspirsobgyraimo.n selective electrode (AMDT-M-2). 9.4 Sample Calculations 9.4.1 Use the standard curvetocalculate the sample value. 9.4.2 Sample Mass Recovered F (ug) = (TISAB vol in mL) x(Orionreadin(gSilonppep) m -intercept) 10.0 VALIDATION a11n00a..l11y.s1iQsDuaaiilslisyttaySrttCaeordntbtyrUopalnCalhyezcikngSQamCplseasm:plOesn.ceTthhee QstCansdaamrpdlceusravreeistoesbteabtlhieshseadm,eeaacshthdeayloowfest rdceoopnnlceiecniatntretaritisipnolionctastnpeeicukenesldseassrsaym.tphleefsirustsetdwotorgepelniecraattees atrhee swittahnidnar2d0c%uorvfe.thEeascuhncdoanrcdencturravtei,otnhemnusattbhei.rd mF1al0tu.ro2irciPedrseeacNniosdtiedobinfofoaeknrsedn2tA,c3r,cefuaernradecn5yc.:e PcSroeemcepiomsuienotdnhsao.ndddaecvceulroapcmyevnatriaensalwyhseisnaanndalsyazmipnlgesaanmapllyessiosfidnifferent 10.3 Other Validation Parameters: NA 03805 5 00001: : DATA ANALYSIS 1L1 Caleutations 114-3 11.1.2 TFoorctahleeusltaatnedtahred fcluurovrei,deusceonrtergarcetsisoinoninatnhaelyssaimspilne,Exsceeel,mevterhsoidonA5M.0DoTrMgr3ea.ter. 112 Analyzing the Data J1re1es.s2w.ti1htahni2n$m20u0%so%tfobtfehaaetclahevaesorttahg0ee.ro9af5ontrdhgotrsheeeatoteuwrto.l.ie"rOAuinstlygirseeruasct"ehrmotauhtyalineb2res0es0hx%ocoulfluddtehbdeeiapfovtiewnrotaegoefotfhtehtohsreeerreupsliocrates noted in the Final Report along with the reason it was considered an outlier. d out in te doe and None 13.0 REFERENCES 314392,4 rReovsiesimoonuBn,tDDeochermmbaenrn1D99X32)000 Organic Halide Analyzer Operator's Manual (Manual 915. A1n3.a2lyzAeMrDT-M-2 Fluoride Measurement by Meansofan Orion EA940 Expandable lon A1n3a.3lyAzMerDT-EP-3 Routine Maintenance ofaModified Dohrmann DX2000 Organic Halide MoREVSIONS Revision Number Reason forChange 00000000000 Revision Date 03806 6 000043 3M EnvironmentalLaboratory Method Fluoride Measurement by Meansof an Analyzer Orion EA940 Expandable Ion Method Identification Number: AMDT-M-2 Revision Number: 0 --- Author: Rich Youngblom Approved By: Adoption Date: /0-4-45 Revision Date: None Grgd] Leader LL/2s Date Qualitiyy ASsuro ancR e AL Lo-#F1 Date Software: MS Word 5.1a DAfofhercmtaendnDoDcXu2m0e0n0tsO:rgaAnMiDcTH-alMi-d1e AnTahleyrzmearl ExtractionofFluoride by Means ofa Modified 03807 1000034 1A Ton SCOPE: Analyzer. This method is for the calibration and operation ofan Orion EA940 Expandable 1.2 APPLICABLE COMPOUNDS: Fluoride. 1.3 APPLICABLE PHOf6.0. MATRICES: Liquid samples in an appropriate buffer solution. Preferred 2.0 KEYWORDS 2.1 Fluoride, fluorine, ion selective electrode 3.1 No hazards identified with this method. 4.0 SUPPLIES AND MATERIALS 4.1 4.2 Orion Orion M9o4d0e9l9990T0ot0a0l1 TeolneicctSrtodreenfgitllhiAngdjsoulsuttmieonnt(ABguCfIf)eorrII e(qTuiIvSaAleBnIt,) or equivalent, 44..43 MOirilolni-9Q4TM09w0a7ter10o0rpeqpumivfallueonrti.de standard or equivalent, 44..65 LMaagbnteitsiscuess.ti bars 44..87 PSlaamstpilce1c0o0llmecLtiovnolvuiamlest.ric flasks. 44..190PoMliysscteylrleanneeopiupsetltaebso.ratory glassware. 555..231 MOOarrgiinooenntMMioocddSeetlilr9EP6lAa09t9e40.00 ESxolpiadndStaabtleeCIoomnbiAnnaatliyzoenrFolruoerqiudievaelleencttrode or equivalent 555..:654 OMIirBciMroonscoRofmStp2aE3tx2icbeillnete53r.8f0a6(coeonrcla4yb8ln6eece(dooemnldpyuitnfueesreid(neogdnlOiyfrinuoesinend3geEdOirsfiouofstnwi3anrEge)sO.orfitownar3eE).software). 6.0 INTERFERENCES &Q1TItwiastrerecwiolmlmgeenndereadlltyhabtrithneg psaHmpbeleattoorpnHeoafr66..00.. A 1:1 mixture ofTISAB and sample/Millia6t:2oSoammptleempteermapteurraetuarsethmeasytaenfdfaecrtdsflwueorriedewhmeenastuhreemmeentte.r wIatsiscraleicboramtmeednded that the sample be 6:3 The rate the samples are stirred at should be consistent with the rate the standards were stirred. CO3808 2 000015 utnderr elbeuctbrboldees. rapped under electrode can give erroneous readings, Make sure no air ist. rapped 7.1 No special handling necessary. 8$8..111.21PLrMaeebpaeaslruatrtheeio5fn0loamfskCLsaalosifb0T.rI0a5St,Ai0oB.n1,IlS0ti5na,tnod15a.0r,1d0as0ndm1L.5pplaspticF-v,olaulmoentgrwiicthflatshkes.date and I8a.b1e.3lePdipfeltastkes0.05, 0.1, 0.5, 1.0, and 1.5mL of 100 ppm fluoride standard into shaappyroouprriiatiesly. 8.1.4 8.1.5 SAhdadkeatphperofxliamsaktsetloym3i0x mL the osoflMuitilonlsi, -Q water to each flask. 8t.h1e.f6laEslkismionvaetrethaierabiurbbbulbebslefsr.om the flasks by tipping the flasks on their sidesandrolling theairin 8.1.7 8.1.8 Bring Invert the and vsohlaukmeethien ftlhaeskfslafsokrs up the tfointahlemi1x0i0nmg.imark with Mill-QTM water, 8.1.9 Record standards in Standards Log Book. 88.22.1CIaflniebcreastsiaorny, remove tape from electrode filling hole. 888...222...432FEIijnlvelectrthtaepferleoewbcetdrrtooodpewsewtoiftthfoipflilslielnaiglngsosloultuitoionn.from bottomofelectrode to wet lower seal, t8sho2em.me8acTntuhofnea,mceuttsueirrnegrassnadinntdshtaerruFdc-stiewolniestc.htrcoodneceanretrtaytpiiocnalsolyfc0a.l0i5b,ra0t.e1d,b0y5,dir1e.c0,t manedas1u.r5epmpenmtFwoitfhonlloowbilnagnk t88i..s22s..u76esRC.leecaonrdthteheelselcotpreodien bthyeraipnpsrionpgrwiiatthe Mloiglblo-okQ.TM waterand wiping the sides down with lab 88..33.1SCtaolriabgraetiCoonndsitatnidoanrsdsfoarreSsttaonrdedaradtsroom temperature. 9.0 PROCEDURES r99.e-11c1oCamTlmhieebnrdsaaetmdipoblnyeattnohdebTeMIemSaesAausBurmreaemndeunnftaecc,tduSsrtetaorn.bdearmdixmeedthwiotdh:TISAB using the proportions c99l::e11c32trAPoldlaelcoieswaitnshseierrstbaedam,rplimneatkthoeemssiuaxrmepfltoheaerraenfdaerwpelsnaeocceoaitnrhdesbusbbaebmflpoelrseetoirnnaspetprhetedinsugtnrtdhpelerateetl.heceterloedcet.rodWeh.en the 9:14 same The rate assamthpelecaslhiborualtdiobne stthaendsaardmse. temperature as the calibration standards and stirred at the 9-15 When the readings have stabilized, record the reading in the appropriate log book. C03809 3 000046 9.2 Calibration AndMeasurement, Using Orion 3E Software: 9.2.1 Calibration: 9.2.1.1 9.2.1.2 PFroelslsowFusntcetpiso8n.2K.e1 yto#88.2(.F4S.). 9.2.13 The computer screen will concentration of the standards, a ask you to confirm the number.ofstandards to be used, Make any necessary changes to nd whetherornot a blank is to the information presented and be included in thecalibration, click on CONTINUE. s99t.2a2.b.1i1.l.i54zeOPdlb,asceperrevtsehsetAehleCerCcetEardoPidTnegiRsnEotnAheDthIfieNrsgGtr.satpahnidcadridsoplnatyhoensttihreplcaotmepautnedrc.liWckhoennCtOheN. rTeIaNdiUnEgs.have 9.2.1.6 Repeat step 9.2.1.4 and 9.2.1.5 for the `remaining standards. 9.2.1.7 After intercept and tcohrerefliantailons.tanRdearcdo,rdthtehceosmloppuet,eirntweirlcledpti,spalnady the slopeof correlation the curve, as well asthe in the appropriate log book and click on CONTINUE. The calibration data is automatically copied toC:\Orion\Data\Calib. xt. 9.2.2 Data Spreadsheet: 9.2.2.1 to store Select either data in. NEW or OPEN from the FILE menutoopen a neworexisting spreadsheet 92.22 Record the nameofthe spreadsheet used in the appropriate log book. 9.2.3 Fluoride 92.3.1 Follow Measurement: steps 9.2.1 through 9.2.4 99.22..33..23 CElnitcekr othne tnhaemNeoEfWthSeAsMamPpLlEe ibnutthteonappropriate place on the screen. 9.2.3.4 When the readings appropriate log book. have stabilized, click on the RECORD button and write the result in the VALIDATION 10.1 Quality Control: 10.2 Precision and Accuracy 10.3 ppm fOltuohreirdeVuaplitdoaatisoantuPraatreadmesotleurtsionAocfcflourodriindge.to Reference 13.2, the rangeofdetection is 0.02 11.1 Calculations Nonenecessary. 11.2 Analyzing the Data None necessary. 12.0 ATTAC HMENTS None 13.0 REFERENCES --_-- 03810 4 000037 I1n3c.o1rOporriaotnedM,od19e9l1.EA940 Expandable fon Analyzer Instruction Manual, Orion Research R1e3.s2eaOrrcihonInMcoordpeolra9te6d0,901099S1o,lid State Combination Fluoride Electrode Instruction Manual, Orion BoREVISIONS RNevuimsbieorn ReafosrChoannge 00000000 RDeviasieon 03811 5 00004% 3MEnvironmentalLaboratory Method Analysis of Rabbit Liver Extract Electrospray Mass forFluorochemicals Spectroscopy using SOP Identification Number: AMDT-M.5 Revision Number: 0 --- Adoption Date: -( 45 Revision Date: None Approved By: Author: Dave Christenson/Cynthia Weber roup Leader 4 Z QualityAssurance Software: MS Word, 6.0 Affected Documents: M-4, Extractionof Fluorochemicals from Rabbit Livers 2; Date Wid Date 03812 0000\ 39 1.0 SCOPE 1.1 ifSslcupoiepdrsef:ofTrorhmiefsdlumboeyrtoshcihonedgmlieisciafolonsrmtuohsneiinatgnoatrlhiyensgieslooeffcFterCxo-ts9rpa5rcataysnimooafns,rsaMbsb/pieZtc=tlri4ov9em9re,toertrho.etThiehnrteetaminasalsluyessiosr 11:-32 MAsatptapnrldiiaccreadsb:Mle/RaZCbob=mi4tp2oL7iu,vnaednrssd:(ostFahlmepruloaerpsop)cr,hopeBrmeiieacftaeLlismvaeosrrseo(sst.thuenrdafrlduso)r,inoattheedrctoismspuoesunadnsd. uids. 2.1 sFpleucotrroocmheetmeirc,alrsab,biftluloirvienrsa.ted compounds, electrospray mass specioscopy, mass 3-1 3.2 DiUnosteno otcthaeurtpuirnoontbhweeiDtphOutmhNpeOvaTobloiTvaOegeUitcC'asbHclaeTpoaHcrEittPyhoeRfpO4rBo0Eb0e,0. tWphsehireenIiFstprhrieesskvsooulfrteealggeeoctecrasibcolavelessrh4pol0cu0kg0gpesdi 3.3 Dfsitonondpotathnedrpurlneulgtehaaesnepduprrmeeppslsautcroeed.rtyhTnehepeslspu.eagkgedtutbuibinngg.maSyecbAeMplDuTg-gEedP.-T1r5oubleshoot back to 4.1 4S.u1p.p1liNeistrogen gas regulated to 140 psi, 44..11..32 F1l0u0ofuiLx ocrol2u5m0nuoL_rfleatquitviaplseyntr.inge for sample injection. 4.2 44R..e22a..g21enMDtiisllultie-Qacweattoenri,trailllewmaotbeirleuspehdasien,tdhiilsumteetahceotdonsihtroiulled1b:1e MwiiltlhiM-iQllwiat-eQrw,ater. 5$.:21 IVSGCTOriSoyr2i0n0ge0 EPluemctprospray Mass Spectrometer or equivalent. 55.33 S1p0e0c0traApdhyesmicbslAyS300 Autosampler 5.5 Autovials or capped centrifuge tubes. 6.1 There are no known interferences at this time. 7.0 SAMPLE HANDLING 7-1 uKnetielprtehaedyexftorracatneadlyssaims.ples in capped 15 mL centrifuge tubesor in capped autovials 03813 000050 2 8.1 Preparation of CalibrationStandards 8.1.1 Sevenbeef extraction liver standards procedure. (See and one blank beef liver are AMDT-M-4, section 8.0) prepared during the 8.2 Calibration 8.2.1 Run the sevenbeef liver standards to obtain the standard curve. twice, starting with the loweststandard 8.2.2 iTnyptihceaslalymeonreansgteanodfarcdoincenrtunraatfitoenr aesacthhe5staomp7lseas.mples. Choose astandard 8.3 Storage Conditions for Standards 8.3.1 pFcerorevfseohrresmdteapdln.adsSatraidmcspcleanreetsrpiarfneudpgaesrtteaudnbdewasirtudhnsteialarcethhNeaOnaanTlaylsryiessfi.rsiSgoetnraantthdeeadr.mdassasrespsetcotroemdeitner is 8.4 8S.t4o.r1a"gBeeeCfonlidvietrihoonmsogefonrateBseemfayLibveefrrozHeonmaofgteernparetpeasration. 9.1 9.2 Initial Set-up 99..11..21 9.1.3 RSeetcosrodftbwaacrkeitnog"pOrpeesrsautree oinn"t,heIoinnsMtorudmeenEtSlog. Fill thesolventcylinder with mobile phase. 9.1.4 psi.Set the pump to "Run". coming out of the tip of Set the the flow to probe. The 1000 uL/min. Observesdroplets pressure should be at 1700 to 1800 9.1.5 ccCuhhiteposcf.kfTtthhheee tftiuippsoesfdhtoshuiellidsciablaietcaftlwhaeittwehinatdhconofoltujhmeangpgrceoubdteee.rdUgaesnsed,Iapfnualelnyytehepcihseiicpleiscaatortechrhfoeoucugknhdftoor 9.1.6 nCtihhteereaopgkpernyoolpuerraikanitientgrloeangrgeotnhu.snudptphley.tiTpoufmthoenptrhoeben.itArogfeinn.e Tmhisetreshsohuoludlbdebeconmoing 9-1.7 Coaurteoffultlhyegtuipi.de the probe into the further. Connect the voltage cable opening. Insert to the probe. t uni it won't go any 9.1.8 aGpoprtooptrihaete"Emdaistosre"sptaog4e2,7anadndse4t9I9o.nization Mode to ES', and the 99..11..190SItfairttisAcnqoutiisnitsiionng.leAsisonigmnoadefilgeonatome",OpMtOio-nD"AaYnd-YseRt S+IRl.etter. Record it in the log book. 5107 samples 9.1.11Run the beef liver samples first, beginning oftherun.. Run a QC running each standard check by running one twice at standard the after every 9M.a2n.u1alDrIanwje1c5t0iounL. of sample into a syringe. Inject thes.ample into the rheodyne 9.2.2 Tinujmecttihoen sapovrte. I1nje0ct0slowly. Record the sampleID in the 523 Wait two minutes, and inject the nextsample log book. 03814 .2.4 Recorodrtheescscaan nninumberr forfor eaeach ch samplpel intheloggbookl. 00005~.1 3 9.3 9U.s3i.n1g StehteupAustaomsplaemptlraeyrA, B, or C. 9-3-2 vRieaclosrmdatyhebesaimnpelaecsharnudn.their positions in the instrument log book. Up to 17 9.3.3 9Se.t3-.u3p.t1he samplPeurs:h the sample bution 99..33..33.32 SSeettsinjaecumlsoapomppslliez=ee2=100uL 99..33.3345 NSaetmCeytchleeftilie:meLi=v0ers 99:.33..33..76 9.3.3.8 PAIrddeedsntsit"fhye Rtshaemupttlroanesystua"trsoteQdueuebypressing "Enter" 10.1 Q1u0a.l1.itTypReuaCnkonahtesritgoahlntdoacrcduervsetryopS tthoe7rusna.mpOlnelsy. tIhfeassaimgpnilfeiscabnetfcorheantghee(ltast50ac%c)epitnable standard will be used. The remaining samples will be reanalyzed. 10.2 P1r0e.c2i.s1iSoeneaMnedthoAdccVualriadcatyion Report number AMDT-M-5.0.1 1100..43 ORetfheerrtoVMaeltihdaotdiVoanliPdaatriaomneRteeprosrt Number AMDT-M-5.0.v1 1111..12 PClaoltcutlhaetsiotnasndard standard. curve, using the meanofthe two values obtained for each 1111..22..2IrCReaeglraceduslspaietoaenktthhoeedimeggthetosrofmriFnaCer-et9ah5esasfnaoirmopntl,hoeerscoaotnmchpeelnretsrfalfturiooornmosc,thheempircianltoiunt.thUesteotlailnreaabrbit liver: `mg FC-95 anion in the total rabbit liver = m gmsg of lF iavnerioC unsfedr- foomrsai9 nda.lcys5 uirsve ~~ x Total mass of liver, gms 1111..43 SPMtraaiknnetdaarcdrhIersDou.lmtWasrtiaotbgelretahmaenfsdotreuandtycehrnuistmaibmneptlrheeo,nswttiuhtdehyptbrhioenotkpo.euatk,sinliatbiaell,eddatwei,thantdhepsutamitplien tohre study folder. Staple all chromatograms together and number pages. 03815 000a052 None 13.1 AMDT-EP-17 Reign Reasonforchange JReovisseion 038516 0000533 5 ee 3M EnvironmentalLaboratory Method Analysis of Fluoride Using Ton tSheelecStkiavlearElSeecgtmreondeted Flow Analyzer With Method Identification Number: AMDT-M-8 Adoption Date: jos Revision Number: 0 -_-- Revision Date: None OOOO Author: Deb Wri/ gCyh nthtia Weber Approved By: up Leader 4a4 on Quality Assurance 2/sf7s Date 1-27-45 Date Software: IBM MS Word, 6.0 Affected Documents: AAnMalDyTz-eErP-26, Operation and Maintenance of the Skalar Segmented Flow 03817 000054 1 oo 1.1 TthheisDomherthmoadnnisfDoXr2t0h0e0an(aAlyMsDiTs-fMo-r 1fl)u,oraidned,cotlhelremcatleldy extracted in TISAB from samplesusing for analysis SIoengmSeelnetcetdivFelEolwecAtnraoldyez(eIrSEw)i.tThhIeSEa.nalysis is performed using the Skalar with an 1.2 Samples can be the Dohrmann. tissues, serum, biological material, or other `materials extracted on 2.1 Skalar, segmented flow, fluoride. 3.1 Follow standard laboratory safety practices. 4.1 S4.u1p.p1liSeasmple cups, 4 mL plastic cups with caps 4.1.2 4.1.3 PAoultoyppirpoeptysl,eonxefvoorlduomreterqiucivfallaseknst, w1i0t0hmplla.stic tips 4.1.4 Cartridge components, refer to the Skalar Methods for components and.part 4.1.5 Snaummbpelresp.refilters, Evergreen 4.2 Reagents 4.2.1 Brij 35,30% SFAS.Detergent 4.2.2 TISAB II buffer solution: Purchase TISAB II from Orion. To1 literof 4.2.3 TISAB II add 2.5 mL or 100 ppm fluoride solution and 1mL Brij. Sampler rinsing solution: Dilute TISAB I 1:1 with Milli-Q water. 4.2.4 `NmitLrsiccoancciedntsrolautteidonniftorircdaecciodnt(aHmiNnOa)titoon,2510NmL(lsab.ogfraMdiel)l:i-SQlowawtleyr.aBdrdin64g the volume up to 1 L with Milli-Q water. 4.3 S4.t3a.n1daSrtdosck solution, 100 ppm F: purchased from Orion. 4.3.2 IwnittehrMmeidlilait-eQswtaatnedra.rdU,se10poplplmy:proDpilyulteene1v0omlLumseotfricstfolcakskss.olution to 100mLs 4.3.3 vWoolrukmiensgosftainndtaerrdm:edMiaatkeeourpsttohcekfsotlalnodwairndgiwnodrickaitnegd sotnantdhaertdasblbey, ausdidnigng the oxford or pumpmate [WoFr--k0i%0np0gppStmamndard TmofStockStandard |mlsofTre ierediae ne Stann dard | with Milli-Q water. Ppipets, to 50 mLs of TISAB and diluting to 100 mLs ---- --obpemm-- --O0p8nm 0 py g] s18 2 000055 5-1 Skalar Segmented Flow Auto Analyzer SansTM System equipped with [SE 6.1 iHnitgehrfceroenncceenst.ations of alkalinity, chloride, phosphate, sulfate or ron can cause 7-1 Swiatmhpilne3s0sdhaoyusl.d be stored in polyethylene bottles. Samples should be analyzed 8.1 8P.r1e.p1araPtreipoanreocfalCiablriatbiroantsitoanndSatrdasndasarindssection 4.3, 8.2 8C.a2l.ib1raTthieonstandards are analyzed at the beginning of the run. 8.3 8S.t3o.r1ageSsttaaCnnoddnaardrdidsstiaarorenepssrteofproaerrdeiSdntacatanapdpmaeirdndpsiomluymporofpyelveenreyvsoixlummoenttrhisc,folarskass.nNeceewssary. 9.1 3St-a1r1t 9-1.2 UCplaPmrpodcoewdnurtehe pumpdecks, air bars and Put the fluoride electrodes in the electrode schaammpbleerr.-pump tubing, 91.3 Tbauthm, on the power of the sampler, pumps, offset potentiometer and heating 99.11..54 TtPuuurtmnthoeonnretahtgeheenitni-telnritfneaercsfe,ainccetohmebpeaufptoperrroe,prdtiihasetpelcaboyotmatplnuedst.eprri.nter. Make sure you 9.1.6 Let the system stabilize for approximately 30 mines. 9.2 S9t2a.rt1inCgreaatReuansample the name of the failbel,eanbdy pserleescstEinNgTFEIRL.ES, TABLE, and CREATE, type in 9:2.2 9-2.3 DPPirRaiIlnNttTth,heesGsaRammpOplUleerPstae1b.tltTei,hnigissnstweoirlttlheedpraiipnnpttrhotephresiyeasnttteiernmeutrmaubbnle,erobfy spaumsphliensg,EnSuCm,ber of 9:2. FFsieWlcl/otnRhdeUssNfaoOmrpUlsTeamctpurlapeyswwoaintshht,htehaesnadsmtpnanludemarbrddesor,onfsoatsmnpeleceeosdn,dtswoafboserhfetishlleeadsn.admpdrliefi.s. IW and 9.2.5 Set the bascline. 03819 3 000056 9-2.5. saSeelylecetbcietngiGnCRtOAhePNHDTaIRtCaOSHL,anPRdAEiNiAnELgLTPaaInnMdeEl.puSIswfhiyitoncugh tFco7a.ntnhoerAgneatlyrseiasltPiamnee,lsooyu 92.5.2tbhUaessebeoltitntheeo.msAmdoajflutlshtsectsrhceerwebdeanr.sievleirnefournitihleiotfifssaetppprootxeinmtaitoemleyte3r/t4o isnecthtfheom 9-28. 3Cthheeicntkerftahceehsicgrheeswt#s3t,andard and adjust the gain,ifnecessary, with 9-2.6 GwlorletnotouCtmObteNouTtnhRe.OA(LnSaelPlyeAsciNtsEoLrPa,dneeaslne.ldectot aannaallyyssiiss pbayneplr.esDseisnegleEctNtTheEaRnalFyrseiesstyhaot 99..22..87 92:9 SPerleescsttSheTsApRacTebtoarsttaortbtrhienganuaplytshies.local menu, pType your ID (initials), the sample table which you created under 9.2.1(or 9-2. 10AafrnetdsessreElsetNcatrTtSEinTRgAtfRhoerTscoAhfoNtiAwcaeLrsYe),,SIcsthSaor.tostehersuanmnpilnegr.wiMtahkoer wsuirtehotuhtattthheessysatmepmlsertaiks u ttK.o the right number of samples and that the sample/wash/ai times are 9-2. 11Select GRAPHICS.REAL TIME to view the progress of the analysis. 9:3 9L-o3a-d1inGagnodtasonldcCcOPtrNLiTOnRtAiDOn.Lg SPteAhleeNcEtDLaA,tUaT-pFOriesClseAthLeCsUpaLcAeTbaIrO0Nbmreinngfoupchthtehelofciallenmaemneu(or 9-3.2 Thioghvliiegwhttthheecfailliebrtoatbieonprciunrtveed, CURVE. ganodtoprGesRsAEPNHTIECRS),,CALIBRATION 99--33--43 TToo pprriinntt tthheelhoigwhlelveevlelsccruerevne,, SETTINGS. Change the max yppuuvssahhluEPeSRtCIoNatTpopgSreoCtxRoiuEmtaEtoNfe,glrya9p0h0i.csG.ioSetloeCetAL 9-3.5 pRCreUetsuRsrVnEENtoTaSEnEdRTpTarneIsdNsGPESRSICaN,nTdacSnhdCaREnngEteeEr.tNhePtromeapsrxsinPvtaRslIauNempTblaSecpCkeRatEoksE4,0N9,5, go to EDIT, 9-3.6 OLoUTprPiUntTt.heSerleescutlsPRg0IN10TECRONfoTrRthOeLEpPsAoNnEoLr,PSRPNACfoErBtAheRL,asOerU,TPUT, 9.4 9S9:.h44u..t21dPLouewttnatlhletshyesrteeamgernitn-sleinfeosr ianppMriolxliim-Qatwealtyer3.0 minutes. 9-4-3 SAffttsecrt tphoetesnytsitoememthears. the lines. rTiunsmedofcfomtphleehteealtyi,ngtubmatohfofnthweeseakmepnldesr., Lpeuamvpe aqnudid in 33744--84 94 STReeallkeeecatsteFheItLehEleeSc,tprupormdepes-sdoeuActkLsaT,ndaFisraobnaudkrssineaan1dt00sQapUmppImlTeFrtoopveuxemirptn-itsghhbeti,pnreo.gram. 9+4.7 On Friday, turn off the computer, display and interface for she weekend. Lov10a.1upQuaalmitoyyConntrol 0000000000000 10-1. s1aiRcgucneinpftiaacsbatlnaetnscdthaaarnnddga(ermdiidnwiptleolahbkieghhuesicegodhn.tcTeonhctoeruarrtsei,moaonin)nleiyvnetghreysas1ma0pmlpselasmepswlibeleslf,boerIefraethaenllyagsted. 03820 4 0000357 10.2 P10r.e2c.is1iSoeneaMnedthoAdccVualriadcatyion Report number AMDT-M-8.0.v1 1100..43 ROetfheerrtoVMaeltihdoadtiVoanliPdaatriaomneRteeprorst Number AMDT-M-8.0.v1 11.1 1C1a.l1c.ulIa'tThieonstsandard curve is plotted by the Skalar software. 1111.:32 11.1. 2Abeltterc.alculations are done by the Skalar software. should be 0.995 or WPrreiptaertehespsrteuaddyshneuemtbsetroosnummarize data. Include sample volume, weights used etc, oSwnoittrohamasaltlruypdayschdkeiaesgtkeaandndodctbuaampceekniutnpstotdahnitedshpkerspiS.lntatucodueytisnn,ottnheiebaoslot,ku.ddyaBtfaeoclktdheeru:ppMrailanlktdoeautt3,a caaonnpddysbopifrnedtahtdeosgheetehtesr 11.4 1El1e.c4t.roInsiGtcuLdDPya,tsaatunddieasl:soEldeacttaroisniccopdiatead iosnctoopaiefdloopnptyodtihsekStthuadtyifsltooprpeyddiinskthfor each 11.4.20ther studies: All datai copied ontoa floppy disk that i Stored inehleabJ.ab. Loarracewents 000000 0 000 13.1 13.2 SDAkXMaD2lTa0r-0MM0e-tO1rh,goadTnshi,ecr#H3ma3al5li,dEeSxktAarnlaaaclrtyiMzoeenrot-hfLoFidlvsueroMraindueably Means of a Modified Doman 13.3 AMDT-EP-26, Operation and Maintenance of the Skalar Segmented FlowAnalyzer Revision Number 1. Reasonfor change Revision Dae 03821 002 005res8 9.3 Quality Assurance Unit Statement 03822 000059 Anachment D GLP Study Quality Assurance Statement Study Tide: Single-dose Intravenous Pharmacokinetic Study of T-6053 in Rabbits Study Number: AMDT-010495.1 Name of Auditor: Kari Rambo TThhiesfsitnuddiynghsawsbereeerneipnosrpteecdtteod tbhyetshteudQyuadliirteyctAosrsaunrdanmcaenaUgneimtaesnti.ndicated in the following table. Inspection Dates Eom To -- Phase 10/1395 10/1995 Final Report Date Inspection Reported to Management SwdyDirector 101965 10/1995 A ~2 QAU Auditor bp55 Date 03823 1 000060 9.4 Key Personnel Involved in theStudy 03824 000061 3M Environmental Laboratory Key Personnel - Thermal extraction followed by analysis using Orion ion analyzer: Jim Johnson Deb Wright Rich Youngblom Deann Plummer Analysisofliver extracts using electrospray mass spectrometry: Jim Johnson Dave Christenson `Thermal analyzer weixtthrafcotniosnelfeocltilvoeweedlebcytraondael:ysis using Skalar segmented flow Jim Johnson Deb Wright "Rich Youngblom Deann Plummer Documentation and Reporting: Jim Johnson Rich Youngblom Quality Assurance Unit: CGyanltehViaanWeBbusekrirk Kari Rambo 03825 00006: 9.11 Data 03826 000063 9.11.1 Summary and raw data; ug F* in whole liver as determined by thermal extraction followed by analysis using Orion ionanalyzer. G03827 000063 SuAmMmDaTr-y01o0f4C9o5m.b1u,stHiWonID6a3t2a9--1L3i6ver As Referenced in Final Report section 6.0 DATA ANALYSIS `Total ug Fluoride in Whole Liver Mean per Dose Group Control Group ug 15.1 10 mg/kg dose (T6053) 12.7 50 mg/kg dose (T6053) 25.5 125 mg/kg dose (T603) 17.7 250 mg/kg dose (T6053) 34.7 03828 000065 FC99 PK n ilvveerrssppkkse3312 lilvvveererrssspppkkc211s2326-6-121 lIieverrsblpaknk2-s132 FaF258285566.-21 FF5522885576..13 FF5s22885s77.23 FFs522806611..12 FFs522886621..13 FFse228s6620..32 lliivveerrbbiikk 21 lfiivveerrssppkk 21 FF5s22886633-21 SFPaK26838-313 SSPPKKe12362-1 SP 1262 PAPctMuFal- % oy iniver WW) 8986%% 016.7080 9819%% 84% 22.1066 418 83% 0a3d1e4 00127520 00.115600 00.115902 00.311810 00233%7 0022119 00345192 so4%% 0182547 00452063 95% 00034905 8%1%% 0197162 w% 218 ApvpermaFg-e inliver bulimveerd Wlhiovelre TotwahloFl-ein weight ver (WW) (0g.r1a2m2s4) (grams) (ug) 0.1499 00..11236227 00..1142622 00.114%99 778 ots 0011328833 777788 154 0164 O012481 777744 127 0011408368. 8767.41 02 0011316958 68611 255 022 oossss 778055 177 00.113085 795 00.11117597 00.11168687 785 041 00112362 778855 347 00..11559235 00..1131933 RPT136LXLS Dosage (mag) 0 10 50 125 250 03s29 Page1 000066 9u.s1i1n.g2elSeucmtrmoasrpryayanmdasrsawsdpaetcat;roamneatlryysi.s of liver extracts This data, although supportive, in the opinionofthe Study Director is not required to reach the conclusion stated in dFeitnaaill.Report Section 6.0, and therefore is not discussed in 03830 000067 HWig 6326-136 PrTsowetaoaycs:oelrNsum;ber: RweRsSapqoueanrseedFVaacltuoer: Amount: oAuva!iyss LWAnaBatBroAam:SeEnt:Fie: TSfiogaelsecDRoesae invsave(Fr0u0s9)Pharmacokinet a1Us0r0sEi.s05 aoniees Fo0A4n0D0s05VTAG 2000EncrospMasy. Coan,A-p\egs DAllstbheesnei4n2 wazlas loCmorraa [[1o0rmogopAz:g j[sooromugzisa: == [[easrooumpso:ng Ped Ton Coun Foss sie Exaact DBaoloern Consuegngesaton tose ' ois Toouf9Trras--ToRFTCIbmbope werTmaeT Trae oor2 Fas sm toon ' 008% 77408 000s Fast 7s vee ' coms sera 000s Paz ame we 1 oan mew ean Fass ae ver ' om sia oot T{shahlecoatuccrlodlnacsbeet.nlhieBrrcYaetsouuulnittwtahpaoflrstiactnmahgiloatcsnhuctnlea7aci]atclemicgbau.tyloTauntoseiwidnncgcaotopnnhpccleeeysnirttnrragaanftldoioaronnrmsduIiclnuahrt8vhe.4eeSsIsantnnaMddnemdatuarhrldodtdcclAuiruMneOegTtsb-yhre.445trh,e0ias-eueil1otb3rm7eye5rr4e45as,oTafihseeeas4ef5woamrstuotsyeddI,n 03821 00006 o Hom hporas 2 li a, BY Crema) 83 $2s 33 = EF EE roay N 699 rl em spre aLIE The16 ts Syston aoa an wor 2g 1915 ona 2303 3778 | A240 gros 2 apa saan SEO 100 E10E ero rs ages 2003 sspggs a7 dT A 143357 aeen A lse8 Goo 20a ioe doc dag zd a age | apap doo oe m Anz 1% (reaqy g8 58> 3eg 33 SFialmemsioesncose cn - ye #4 100 we Lie. 4 . LADUE Tho 1SrDaste systen 06/04/1995 60:14 WE aggre ae A me Mig a \ on . 2 WE2 ug3 wwo ERR SE { | 2g sE [Saami7% con Le - ae LOB:E- Tho15BbuiteeSynsto,n ug 1600 apre HE arson anise ag Pr - Cb ow | . a Row al om) am 135 urs dy 135674 i3 fe : 5&& HE appa lef ba Tage | A AA | em "oa oe a ER 8 Lo SE I 0 Bete Stn ows maa loo wap igEgigeRS. a 3330 , Aisi bes] 02 em 3I \ om 57 a \3A an \ V mm A as\ ve oF Egg & am m JF I eg es & ae Kiel | Iso a5 mSeaJ n aa\a seme" Itr soSeesya < g z g3 Be coy 12038 - oEAT pera SIO, Pata ten si rsa age Ee J wy we Ge ; La 2 L i 33x7 sae A I He ju az7981 4 \ Clobisy - A R 388722 "E . MetOhpSoeadrmapCtl:oeDrLCLIV Run date 06-23-1995 09:19:00 version: 16 StraiPgrhitntLeidneonFi0t6-2f3o-r1c9e9d5 tAhTro0u9g:h19Or:i1g3in. Component #:1 A-7 187849 127117 67871 + 7 8 1.2 1.6 AMOUNT Tow LEVEL AMOUNT EXTAERRNECAAoLmpoSnTeAnNtDARD1 CA=LIBRATION 21 3 01..82000000 1.6000 12677101771 1870439 4 4.0000 388722 Y= SLOPE + X 4+ INTERCEPT AmouAnrtea = R squared 1=.0091.89E8-2045E+0*4 = 0.9816 + AArmeouant ++ 00..00000000BE++0000 Lies fue 4 HLA 03837 000079 9.11.3 Summary and raw data; ug F* in whole liver as determined by thermal Skalar segmented flow extraction followed by analysisusing analyzer with ion selective electrode. This data, although supportive, in the opinionofthe Study Director is not required to reach the conclusion stated in Final Report detail. Section 6.0, and therefore is not discussed in 03838 000075; RE: 6329-136 LIVER SAMPLES AMDT 82495.1 Date of Analysis: 4-6-95 Analyst: DDW rales Qa) The samples are burned in the Dohrman at 950 C using between 8.1 and 8.2 grams of the liver. The gas is collected in 1.0 mL of 1:1 TISAB/Milli-Q waterthen an additional 2 mL of 1:1 TISAB/Milli-Q is added to allow for sufficient volumeforSkalar analysis. The samples are then analyzed on a Skalar Segmented Flow Analyzer using the lon Specific Electrode (ISE) Method. TsIySsAtBebmu.ffTehreissaamdpdleedtthoeneagcohessatmhprlouegahsaithepraotceedemdisxitnhgrocuogilh the before the potential between the ion selective electrode and the reference electrode is measured. The signal is amplified and related to the fluoride concentration. The instrument was calibrated in the ranges of 8.815 - 8.15 ppm and 8.15 - 1.58 ppm fluoride. The standard curve for the high range was plotted using the inverse logarithm option. The standard curve for the low range is linear. All standards and samples were then calculated by the Skalar softwareusing these curves. All results below 8.8081 ppm appear on the raw data as #.###4#4, A quality control standard was analyzed every 18 samples to check for accuracy and drift. Raw data is taken from the appropriate calibrated range of the Skalar printout and summarized on an Excel spreadsheet. The sfiunbaslerqeuseunlttsdairluetiaodnjsu.sted for the collection volume and any Qt Que 03839 00007; Pods `S-AoDsmpTLiaIAaVtRoYEso.R1FS BESTCOPY AVAILABLE mGionwt mewee leGowe:s BFmaamm2a EGomH s mas Tuas bciGoodiwieg BmEmAIaT metGoriowosmne mFTuaEe0isl oonw 0Jo sohmee 3ww Tmemw 03% ow GoSnem J30o% hoownee 1i0m on nfpaiea 2 ow ew Tm n E3 Aoohwes w ow wm 0 HE Now 200 oolwss M ow w pnBmaaseo B woow w aoommm 03Jb oohmeme ooonmn ax Bnwean 0o8w ow g 2 p 3! 3g8 Poet z5# m seroion outersous aun Peoee srs pA suDIEA R 30061 BESTCOPYCOPYAVA AVAILABLE DPP Coote shee io ems imoe omom os wm SoSDoooosmmSmmoonwoormyoaooamoaew owem WB oF ooorms t eoope oomn I} me FWF RE omEe vo rrmee Ane5 om B0 onoem ooaw noeenm ow 5BBoo ra o3h% haanns oooisn % BBBooodooimmn Boom oi1n onnen iw me Wwwm Books owes 8F5 EaEn FEOe 8 w8o uw BNoohnme 00 ome o0pB emmE Wo poe ww 253FI moahy $5 wma 52 0 5Booomoem Bowe loow mnawe ow ISah himeaem =5 oBooomme 1 om om " Paget $i.3r i2aE5iEf as as o5 gmts2 seus F P33E E me B FFAI e FnaoA on OoTwT oaooann BBNPE OuoMmmS oi0en nnwewaeoow& om anos am am ou now ol 2 oo amos on mw we -Wa N0Nn oaaowmmm DDLooo > S40. dedo e is iinct,Dig msfo edn DOV 2g 33 sg N == Page2 1995-04-06 16:07 OutPut of : 950406C1 Softwar:e version 6.1 c1990,93 Operator : bow Date of the Analysis : 1995-04-06 13:33 Analysis Pile Name : C:\SKALAR\DATA\950406Ct CPlauloirbirdaetio1.n5order = Inverse Logarithm slope i 8 = nasser Result = 10l [ -- x-] a x1 5 == = cSclooorrprreeeccottfeeddtvvheaalleuulseecootffrottdhheee aaiz == 20 = -00..0000000903 1.24069 CFalluiobrriadteio1n order = 2 Correlation : r = 0.99926 Result = a2 % x* +a1 * x + a0 aazi== a0 = o00l.lo00o00200s02z05 sampler TyNupmeber i+ r5A1000 WSaasmhple TTiimmee Ar Tine :: 15200 sseecc.. 1. sec. sTaPkeeciaulp needle Height +: : SNoinnegle 70 mm. Diluter ddniielleuudttliieoonnHeiVFgoahlctutmoer ;: ; 8100 2.5 mm ml. DRieslaumtpiioan runs :ii1 RUesperrocfeisle :: No . mr ow uot HOE csaomnpcleentration alas 02495. C328 1 03843 000050 5 1995-04-06 16:07 output of : ssososc Fluoride 1.5 DesSPcyiasgottnhleaomlnruhmtubynepbreer {t|. v0Dee3sbubbled lRaieutsatmTephlreesnota |i4No0o0s Waiinsdoouwtpsuveent o0re 5512 ssstttaaannndddaaarrrddd |: : IIIgggnnnooorrreee 5Si 6 ssSTttaaannndddaaarrrddd ||| IIggnnooorrreaeso 85597 sasTtnaanndddaaarrrad i|i 10o..i3800e00 OD5ri1dm0eern'sS:iToannTdasv: reaPrsPsi Loga1r3i0t0hm PstetraaikxgtgeshrVaavlLeu'iemit |||: P15o00t00n0tepSsuec HNsoata'asrutrailgownnoiornredeow ||| 17G5o2..0 SS4eecs FiRfoelrgtmeeunrtearatiois n i| tNoo output anaes Fluoride L DSPoaictgohntaolnrumtbypeer i|: Deebubblea alRSetyssuattmoepnlesumbor i| NN0oo Waaiiin)dooTwhurteevspennoutlta:|| o04e0s9s 03844 000081 1993-04-06 16:07 output of : 950406c1 55s32i ssstttaaannnddadarerd|rd: 000..l00018%5 68S5i ssstTtaaannndddaaerr|ir|da 000.1.1102%%0 558987 SSStTTaaannndddaaarrrddd ::: IIIoggnnnooorrreee DO5ri1dm0eern"sS:iToann3da: rapp| Ignore PEsetraaikrstg`esrvhaaplLeu'iemit :i:1P85o00i00ntepSduec Mosnetaah'srutreiiggwnnioonrrdeeow :[G1o73.50 SSeecc FfBioolmgtmaeinriearatio+ nchit:iNcrdoo outpace ibeed FFlluuoorridiedLe1.5 Poonn PosTyp 1dent Dil Weight Ch Result Dl Cor. Valu Time iw Initial Wash FI Tracer 1 1 1.000 1.000 3s3 o10.o.408o597 1o 1 o 22000 25278305 6s 215 2a Drift 1 1.000 s3s1aa.bs3i0sa8 00 23z33e00e 25990oo 10)olpp 3 ow Wash 1 1.000 s3 o0o.0s57 o 1 o0 3000 629 . 4 SL standard 1 1.000 d3 o0.0i64 o1 de4p 34s0 77%3s $52 Stamdaaz 1 1.000 s3 o0b.0s7 10 110023 402`5 912 6 8 standard 1 1.000 s3 od0e.e0r8 o1 a2;11 s125110%80 7os4 standar4d 1 1.000 [3 E0X.0T5 I1 313 616 1261 85 standards 1 1.000 E3 X0T.E12R0 1 40s 708 1436 o 56 standaras 1 1.000 t3 oi0s.o5z4 01 a4937 sod01%612 03845 1087 standar7d 1 1.000 3 0.287 1 63 1178 1786 " Hose standards 4 0.2868 1 1.000 3 0.605 0 863 o 0000s 1 1387 1726 1962 1 12 89 Sundards 13830 Standard 10 1a Drift 5 ow Wash 1 ou E251 1 ou esmse2 1 BLANK Iu ses 2 uw 2051-2 2 ou 28573 Zw P2061 uw P2082 uw P206-3 2 uw ses 2% a Drift 27 w Vash ou ES2062:2 2 uw Es2062:3 ou LIVER BIRD Bou LIVER BIKZ 32 uw LIVERSPKI 33 u LIVER SPK 2 1 1.000 3EE12X00 1 H20R83 2402 2136 1 1.000 3dr1o.a48r8 01 2a2m5e6 26160 2312 1 1.000 d3 u1d.e58s2 o1o 2733772s 2660 2ums 1 1.000 d3 o0s.e05s7 o 1 o0 206C57 277 3 1.000 3do0n.i8z9 o 3 aa4 aa5z%ene 3 1.000 3so0o21s2 3oess 4000 3%00%8 1 1.000 3sol0d.s0s8s8 01 z2o0es 5157 a%ter 3 1.000 3Go0l.s3 3o 2592 6000 3360 3 1.000 3fo0i.l37s3 o3o a3s%s eas73%836 3 1.000 3so0d.0708 30 1165 32003%67 3 1.000 3Po0l.7e8 o3o 115 32083%869 3 1.000 3Po0.i18 03 14s 352TE 40ss 3 1.000 3so0.0z01 03 774s sa0442%3s 3 1.000 3so0d.s8 03 33s ass0M aan 1 1.000 E 3 1.R555 E1 2H34H5 2657 4ser 1 1.000 3so0o.z05s7 o 1 o0 31574%78 3 1.000 d3 o0s.i1838 o 3 z20 3400d%ea 3 1000 P 3 0E8RC3 H2E7 3S3 ] sto 3 1.000 3 oes 3 33 a0 sas 3 1.000 4 0.0113 3To0lems 0 53 33 0 0 2341 320RsGas o3s16 3 1.000 B3 o0d.2s5 o3 i1s30 4965s%637 000083 3 1.000 3 0.265 3 208 512 5807 % 3u 35 u 36 u 37 wu 8a 39 w 0u au 42 ou 43 a "ow WE Iw FS2863-1 FS2863-2 S2863-3 SPK 63-1 Drift Wash SPK 63-2 SPK126-1 SPK 126-2 Drift Wash Runout Wash Tues 3 1.000 34000.22076 3 1.000 43 0.00.225030 3 1.000 3to00.220s0 3 1.000 43 0.00.28629 1 1.000 341.10.586%3 1 1.000 43 0.00.002597 3 1.000 3$0M3u5lt7i 3 1.000 3 multi 40.3518 3 1.000 43 0.M3u5l0t6i 1 1.000 43 1017.57464 1 1.000 43 0.00.002557 1 1.000 13 0.00.002507 ou we wy 03 a8s4 384o5o085 03 esss 384o6p153 03 7722 36806%336 03 221155 512o6p510 01 22335584 26440 66s0 10 0o 288To 68610 30 M 1G00220 13600 71030 3M1018 1388 7260 | 0 1018 0 oo 03M 999922 13920 7344op 01 22333366 2752o7o558 01 o0 448To 7743 1 o 0140o5 8o033 (mky t WK ql\as - 03847 00005 a [ert cre of sve Fieri 15 ---- ; 1 own = Hl ! Co / | |l]Lo o] // aI i I| | / [1| | |gH # Hy | I |IIl Lo | ed [ | /J | / iI | 1|| //// !I| 1| 5 |i | LoJ| 0o.0c5750t8 0 eOrrder t: InmverseeLosraritshnWeeasoried omsascirwaiuws ooms|| ||| atibation cure of 5500801 Fluride L || 25270708 | {| 1| Al s/i|dG0asas !] a | | / 00008 i| / ow | Ph | /// 1I [| [o || /// [] iPl CoLo -he 1| lBnow" || | E| E rt + 2 room | |] | I~ | |so PEWTOT NH7e0 IR Ur -- meA -- | | iy [ [] Ll | ] LEH Lil ii fom i Hib wfpon Hh Hi whi Poto | | | |goasas |Iose or Ho ` |i | 10 Hh eqiH Hi hoi vod LL esr [pA ati te ee | |lo egiy EE Fe r toE dota ofa0T1 Flcride 15 I| ~ || |Io || / ll || |Ue ) 7]i I || | |[3i ro ||| IIi l:[| lLo]odIt | i i| |L !Hl anne Hi IIPo ll n ib . RARE iI |] |eE) VElReEaTTama TI [idJoos [o | 000087 Esc=Exit i Fi=Help | Crtl-P-Edit peaks | WV