Document Rzoo0DxMkxw05oqryqOeO2gk

AR 2aR6_ 3313 . 495 AR226- 3313 piv Supplement Number | --~ TRADE SECRET Study Tide H-25509: Repeated-Dose Dermal Toxicity 28-Day Study in Male Rats Supplement Number 1 TesT GUIDELINES: U.S. EPA Health Effects Test Guidelines OPPTS 870.3200 (1998) `OECD Guidelines for Testing of Chemicals Section 4: Health Effects, Number 410 (1981) AuTHOR: Carol Finlay, BA. --_ STUDY COMPLETED ON: August 4, 2003 `SUPPLEMENT NUMBER 1 COMPLETED ON: January 14, 2004 PERFORMING LABORATORY: E.L du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.0. Box 50 Newark, Delaware 19714-0050 LABORATORY PROJECT ID: DuPont-11763 --_ -- Peres Company Sanilized. Doss nol onntain Tema A) Company Sanitized. Doos nol contain TSCA CBI 2525-5D0a9y,SRy eMapleDoResesDaermtalTeody SupplemDeuntaNnu1m1b7er63 ~ QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 25509 DatesofInspections: Supplement Number 1: December 12,15, 2003 Dates Findings Reported to: Study Director: December 15,17, 2003 -- Management: December 15,17, 2003 RepoB rted by: T Qual`iWtyoAnsdsaurancellAuyditor 14-Tap.20d Date. --~ --_-- CompanySankized. Does not contain TSCA CBI 112505 pppnDostDe Toi ~ Sooips CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. sma, Lo foEa e y nw- my Issued by Study Director: fLianpd8ely dchlen. 1L4t Jadnentay - ~ CompanySaniized. DonotecontsainTSCACBI 216.2-5D5a0y9:StRuedpyeiantMeda:lDeoRsaetsDermal Toricty SupplemDeunptoNnutm-1b1e7r63| --~ TABLE OF CONTENTS Page QUALITY ASSURANCE STATEMENT craves 2 CERTIFICATION cscs 3 Bg REASON FOR SUPPLEMENT NUMBER Luvsosrsssssrssssasssmssssies APPENDIX A ANALYTICALREPORT mrss. --~ ampanySaniized. DossnotcontainTSCA CBI -- -- 21.52-5D5a0y9:StuRdeypeinatMeld-eDoRstesDermal Tosicty STUDY INFORMATION substance Tested: (NEN SimonsCotes: ge Submitters Notebook Number(s) {NY Haskell Number; 25509 SupplemDeuntpoNnto1b7631 Sponsor: E.L du Pont de Nemours and Company UWiSlAmi.ngton, Delaware 19898 ~~ Study Initiated/Completed: 22-Nov-2002/ (see report cover page) Eompany Sanitized. Doss not contain TSCA CBI 0 A A 2H-82-5D5a0y9:StRuedpyeiantMeadlDeoRsaetsDem Toxicity SupplemDenutPNounmtbe11r763 REASON FOR SUPPLEMENT NUMBER 1 `This supplement contains the resultsofthe analysesofplasma samples collected at terminal sacrifice and analyzed for the presence. oN, `Egpay Sanitized, Dhe otcos ntaln TSCA CBI rere ------------=--eee rep-- 2H-52D5a50y9S:tuRdeypeinatMeadl-eDoRsaetsDermal Toxicity `SupplemDeunPtoNntu-m1b1e7r631 -- SUMMARY `Aper28g-rdoauyp dweerrmealextpooxsiecdoldoegrymsatluldyyfworas6 hcoounrdsu/cdtaeydfowritah tmoatalleofC2rl8:CcDons(eScDu)tIivGeS dBaRysrattos.doTsaegnesratosf 0,5, 50, or 500 mg/kg/day H-25509. The groundtestmaterial was mixed with mineral oil, applied to the shaved, intact skinofthe rats, and covered with occlusive dressings for the durationofthe daily the conditionsofthe exposure. study, the All ratswere sacrificed at NOEL for toxicity was 50 the endofthe exposure period. mg/kg/day, based on decreased Under cholesterol at 500 mg/kg/day. ofIntahdedietxipoonstuoraespseersisodm.entWshfoolretobxliocoodlowgaysecnodlploeicnttesd,obnlosotdudwyadsacyol2l7ecatnedd rfeotraianneadlyfsoersaantaltyhseiesnodf total fluorine. The whole blood was analyzed by use ofa Wickbold torch combustion method and an ion selective electrode. The limitofdetection (LOD) for the method is 0.5 ppm (500 ppb). At the 28-day sacrifice, blood wasycoslleQ cted, cs entrifugcexdi,raacntdedplfraosmmaplreatsamianebdyfporrotein precipitation in acetonitrile. The compound was quantified by liquid chromafography/tandem mass spectrometry (LC/MS/MS) analysis using selected reaction monitoring (SRM), ~ sQtuaanndtairfdi.catTihoen lwoawserpelrifmiotromfedquuasnitnigtaetxitornac(tLeLdOcQal)ibfroartithoinssmteantdhaorddsisco1n0tapipnbi.ngReasnulitntsoerfntahlese `analyses are presented in this supplemental report One sample eachofthe stock mineral oil and stock dressing material used to occlude the test sample application was also analyzed for the presenceof total fluorine. The Wickbold torch combustion method was used for this analysis. 0T,h5e,l'f5f0f,lalnldev5e0i0smign/pklga/sdmaayw, erersepectiv61.e4 lpyp.b,T1h5e5.t5otpapl bf,lu1o3r1i5ne.9lepvpebl,s and in b 14176 ppb for dosages lood were 1075 ppb, of 1470 ppb, and 9316 ppb for dosages of 0, 50, 500 mg/kg/day, respectively. All total fluorine levels at mg/kg/day were below `mineral oil and 1760 ppb fluorine the limit of in the stock detection. There was bandage material. 500 ppbfluorinein the stock o`TfhEexryesguelntsorefptorhte).anTahlyesriessuolftisioiffftJhffearaenasluysmimsaorfitzoetadlinflTuaobrlinee 1in(btahseemdionenrAaplpoeilnddirexssAi,nTgambalteerIilal are in Table 1. The analysesoftotal fluorine were in the originalreport andhavebeen included in Table 1 for comparative purposes. The detailsofthe analysesFF conducted by Exygen Research, are reported in Appendix A. `which were _--mm---- Company Sanitized.Dossmot containTara ray Te B2H8:D-25D5ya0y9SS;tuuRdedypeoinaMtMeaidl-eeDRoRsaeetsDermal Toxicity -- TABLE | S`wSpuplpelemmDeeunPntoNNnutu-mm1bb1ee7r6r3]| MEASURED CONCENTRATION (ppb) Blood Analyses Dosage (mg/kg/day) WHOLE BLOOD FLUORINE* prasva (| MEAN SD. n _ MEAN SD. n 0 1075 5 <500* 50 1470 500 9316 Number of samples S.D. = Standard deviation * All values below limitofdetection. a LOD = 500 ppb b LLOQ=10ppb 7000 5 00 5 3086 5 S245 614 229 10 1555 255 10 13159 4823 10 14176 45340 10 --- --_~ SAMPLE ANALYSIS SAMPLE Mineral Oil Bandage Material TOTAL FLUORINE (ppb) 500 1760 --_-- `=CoRmpYanySaniizeeGd..DDoossnoOtrconitaein TsScCAaCBI 12.52-5D5a0y5:SRtepeiusntMdeadly-eDaoRsateDsermal Toxicity -- SupplDemuepnot nNtum11b7e6r3 Ps APPENDIX A Analytical Report --_ -_-- CompanySanhized.Dossnotcontain TSCACBI 2P 5.Day Sudyr inMleRats------ SupplemDeuntpounmebe11r763 STUDYTITLE 52505: RepssdDoseDecaToxsiy2DaySyin ile Rs. RRAETQAUIREMENTS Anyi Method Recurmts STUDY DIRECTOR Cari Flny ---- ANALPHY AST ECOI MPC LETA EDOLN --- 'BERFORMINGLABORATORY / TESTING FACILITY 3E05u0gReneReasaDive SPuhtonCeol1e8g,27P2A11066301 STUDY SPONSOR .1dsPoNret wesNeDFmEoo1o9ar7d4C0om0peUnSyAD3) PROJECT SYe:-- Dupon 1765 Towpage 72 To BompanySaniized. Doosnotcontain TSCA cer ZD218u.2-y5D5aS0y5u:SduyRdeiypneinaMtMaeadle-eDRoRasaessDem Toriciy SwSpuplpelemmeDennutNoNunummtbb1ee1r7r63|l GOODLABORATORYPRACTICE COMPLIANCESTATEMENT AEPAvTSC-- An(40-- CFRp-- ar:752-- )byE. xyfpoernDR"uFe-ss2at5r5,c09hw:.asReppeersfioerdm:eDdosinecDoemrpmlailanTcoeriwciitthy U25S- Facipaxl ExpRescue CaSrtuodlyFDiiraeecytor Dupont Vi5ck Rep onadyry `DSupopnosnotrReprsemaive pBud ln D1ue. bet 1003 Bu9e-0cr- 2003 Exypn Research Pez SC------------Lo-- mpoarinG y.Soano-- iotiizetG d.tD t.. sonioits . cioints sa. iin.T.So. CmAsCBi. I . 12.82-5D5a0y9:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity SuppleDmuePntoNnun1b1e7r631 QUALITYASSURANCESTATEMENT pcEhnxaytsgleedsnw,eR"er2sr5eea0vc5i'o,sweQRufaoelriptcyoendsubocotsacDceoraUdniiangtTsooeErxyygenResearch'sStandarlcdROpearating PrAoclefdiunrdiensg,swheerSrteapyrPrtoocth,e aSntdudaylDlsneptloartndG10omoaLnaabgiomresneyPraciceSanat us LoEfnesiinnd osDiieel DueRepoedtoDuetoRBeypmaos Pool| Mus SDuulsDReipoorerdaio msi SeovseManagemen 30 Sed osnams woe 2 mwDmaDan mmm wm ovis canons `Report Review SRARnweyiDincaaisRTepaalt om ome oom oan - a J Lid) LQuaai AsrnceAudie Daeotlaslo PP. --_-- [---- Pesan EompanySaniized. DossnotconTtsacaicanr Te RT Sapay - --A r CERTIFOIFCAUATHT ENI TICOITNY Tere,reAI p-- N mGoiTpe Smet Prien cmsrovaction gS0irgi i ge rt -- --~ -- nASLdie) 5bk iyDi ee =RAM pdt Moe 14. 6c t3 y SmeeResi, es E a- e Somes Jet . -- i CompanySanitized.Doestotcontain TSCA CBI ZD22y85-S5D0au9yb:SyRtmepuMienaidMteledye-RDoaRsaessDermalToricty SwSupplpelDemmueepnwtoNNnuutmm1bb1ee7r6r3l STUDYIDENTIFICATION 1.25509 RepetedDoseDermal Toiiy28.DaySrdy inMle Rats SPONSOR STUDY NUMBER: Duo11763 TYPRORSTUDY: SAMPLE MATRIX: TEST SUBSTANCE: Resitue RatPlan LJ sponsor: EP.L0.d8o0Pxo5n0t de Nemourssnd Company NePhwoaner:k(D00E2) 136957.154205550 --_ STUDY DIRECTOR CDourboonFtinley TESTING FACILITY: ANTIAMLEYTTAIBCLAEL: PASE Ex3S0yt3eg8 nRCeRoselesaleraergDcerhivJeest `AsAunenyaanlyyaiSTnermDiDnaaeei:on Dies o0t7ir31nm0a3 Aviva Report Compleion De: 1310x Bove Rant san r --e ------------AT-- H Com-- pany S-- anitize-- d. Does-- not con-- tain TS-- CA CBI A oiyRE eeo , 0 ~ sSeo--pp--t ---- [PROJECT PERSONNEL iThekstiy i Soier tmsc teHEyAelon re SO -~ oy er kets ikme me Totti Som mi I ~ -- - near {EupanySaniized. Do notecons tain TSCA CB ZD22u85.S5D0auy5d:SyRuempiMencsMatldye-eDRoRasaetssDermal Tricky SSuppplemlDeunptoNunutmb1e7tr63 TAOFB CONL TENE TS GQOUOALDILTAYBAOSRSAUTROARNYCEPSRTAACTTEIMCEECNOTM.PLIANCcESoTAmTEeMErNT Page ~~~" 2 60DESCORFAINALPYHTEAILMEOFRNOD rh] 62Prperionof SarssndForiesionSoon 11 ~ 66.65QDueesnciritpaisoonnAof0IdEmxeilne5AdOlprusnincgoCeorenroe-- enre ----13 8500 RCIESNIULTTROSEF.TC .HG.TEHDUARATTAMIMAYTcHSoArVYrEeTAFcFeEAcCeTEeNDcTrirCerGUoArELmIrTeSYOF 15 110RETENTION OFDATAANDSAMPLES _._crsorrrr 15 LIOFS TABT LES TableL SummaryoN (ng/mL)in RatPlasmaControl Page Samples.. 17 TTaebllee.. SSuummmmaarryyooffRReecsoivderFicosuOnfdQocEAR)EiRnRRatPIiansRmaaSEmlpaIsESSc eleee1189. `TableIV. SummaryofResidueFoundfol (ng/mL) inRe-ExtractedRat EyeResch Pron -- Aee es-------------- TEeom--pan-- y `San-- itized-- . Doe-- s not-- conta-- in TS-- CA CB--I Er ~ ~ | -- Sr EoaLr OI FFS IGUT RmEr-- Sa pt ne hoe pa ot es ore. PA of born 28 Port. Copp5 agea oifCeeA es-- ce l-- il -- ofA5 ti Sa LAIPSI TPOEFA NDICE ES eR----i. AppendiBx ob SN rota - nnn CompanySanitized. Doesnot containTSCACBI a 12550l 9 ReeDpeDec aTotit - Spe--ma-- S-- 1.0 SUMMARY re B-- xygen Reseparcohto(cEoclyDguePno)natn-a1l1y7z6e3ds(aAmpppleensdoixfAr)atupsliangsmtahfeo`rarnaelsytiidcualemsoetfhQoEdSN ellste rs tis 0 wih ot Bt themethodvalidationstudy EER . iting * Residuesof Qn thera plasmssumplesrangedfom 19:3 nga.to 26000 g/l. Theaveragerecovery standarddeviationfor SRB fortifiedratplasmasampleswas. Teciteof i isev st lesg id 20 OBJECTIVE Exygen using themethod GRENMN Determinationof(EN cuilcd "MethodofAnalysis for the Scr. byLC/MS/MS" -- 3.0 INTRODUCTION Ea ome emei A Neer220 wl tty dee `"aTnhailsyrteipcoalrmtedetthaoilds(thRe EresNultEs oEftheanalysisof atplasmasamples.for@MMsingthe `ThestudyDuPoatw-as1in1iti7st6edo3n Nov2e2,m20b02,ewhrenthestudydirector 1L h co eTmar!mBeec40s TEeSlTkeSsYdSTErMrenoyrcoamt4 ocriiend igs ST S ip onT nd hinoSy eotetyyolioreiioCccnomnsffrdntreosopccee Simo rsa CompanySaniized. Doss not contain Tsca car 2H8:2-5D5a0y9:StuRdeypeinatMeld-eDaRsesDermal Tosicty SupplemDeunptoNnutm1b1e7r631 50 REFERENCEMATERIAL TQoooewhear y52s00anrdmarQa roosret caieExivys ngeeenodn oS r <iE iEcygenonFebruary20,2003 from fTshiernaedviwaslsofroerdmaestiicoantefdointe recgeeascte amnadiahel csolnieststbeslow.as Toheesaly] ilk ExpenlovenNooy LoiNo. Purity (%) Expiration Date wo Thestructure of EES 1: t:incl sundad we given ErynReh ~ -YY Pam 10072 Company Sanitized. Dees not contain TSCA CBI 25Day Suda mie Ros---- SupDpenrt a1r17e63 - (my) 0 DESCORF AINALPYTITCALIMEOTHNOD 61Etraton Procedure 1 2 M2etcrvey0e1 tin aosLri .oFofarscepctoeh onovtilemk.tmpec mtndcweconensnit e00bs3s5 ort nt 5. fACrrioenediswoiinmrtane1L00nm.. 62Pretest ofStandards ndFutonSato ofspr00sfalibymormogcenys of rin `Thestock standardsolutionof@NFwaspreparedonMay21,2003, a aconcentration Sp I (ecotmaecntmedo eofe norMpauia rcoii hntyU)17 inBn 1m30e1t.Sh50anol41s .0bepTnhteoars1twodcok0s(te 0acondfosarspdssTfooolmurrtpirotoen sofnW2Eon hE.SpawAas _ gtennohenvtawmo 100 wac rev byaking 08 mo em 5mbAas1nen0teoor0,fsTytaeands.arMsdscoaontnatiniwonegs(nEe0Ed3twoiteh8inyteprennal.ae GMMRwasl preparedbyd dilutionof TEE ae De A 100 or fr othm ofeiEve1a0e.na0 tdy 5oes,sOnO01Mo:oir 8v100 001 wit TomecstiioTonhenSxasdaaancsSenpasctsS SadyoSgshcreossinaneidnsG,asn deunmbe edat Bupa netian ~~, --- CompanySenitized.Doesnotcontain TSCA CBI e H2-82-5D5a0y9:StuRdeypeinatMeadl-eDoRastes.Dermal Toxicity e SwSupplpleemmDeeunPtnoNNnuutm1mb7eb6ra3|l ~~ -- dodneysNScMzotohedfolliowinng(aTgthke:forlicaonofthe andar befor exactions FI orQifcuEton Von (I) SurnCploerw(lnly ) CBaair mrseieodn Solon Standard a ooorr 00 a01 250 --ol001 0 =10 owoal1 a01w00 sToelhuedtixootrnaahcedtodbneiatsgciountgistcnvhwevanos.lpieaored0by100mkiLnwi0t.5hsmcLoonfchee.T09h8s sooluttioGn wHesG iTbnhs osutfnorcdgkiestrtahtnerdrar(vd4sd+oltutsiCo)noachenalowftitnohwtx.freDpcorot.actuismotaonlefdascrandnsldtoaildaorrsetpwuierirtieisoooncrcnnan 63 Chromatography QoTufhtnehieitcLesOniQoonsnttainned)i thecsoncroml~p2sl0eimsnhiines.dcwobimyteasolpoyrssiigsrniifocgtaenesleehcctatroeysnprrgaapyteLiCosnMs(SI2sM0S%, 4 InstrumentSensitivity `T1h0ensgmialnlLestamount of ilinectedduringthechromatographic runwasequivaletto 5DescriptionofInstrumentaad Operating Conditions DaeActqPuailEseiStdciooenpxsenrLdaCipnMrgoSccoeInsMsdiiSntgicoownuespsleeepdehrtfeoodrmHbeeedloiswi:tngAPnacaklayrtdH1.PLsofstywsatremwsused. Dita MaIesfscSep:eci CSoomfputtwear: TPSCEeISoECXIlToEnuXSbApoPralLyo4en0mS0pp0erByeitLrioeouma=do3I5nl0rMoeadCuswctsiiuAtohnlnXH2aeysrte7se in PDeElSlaOspsiAemaOtX1V5ersion 12 Ege Reset Pe 2072 - CompanySanitized. DoosnotcontTSaCAiCnBI 2182-5D5a0y9:SRtepienauMteaddl-DRoaystesDermal Toric SuppleDmuepnontt-u1m1b7e6r3 mo HewetHHPPPQcVuatcuu(PmHuFD)peSgeisser1100 HPLCColas: GeneEsHCPPyCAoovlncueismnnCCtoohmrparrmoentm2o1gmmbx5g0myn,4.. CMooNbliulomenPPTahbeassmepi((s5A M2l3e7mtMCeaAlmmoniumAce inwater T3in smoe wBAo 1%w0oB0 Flow(m00l33/min) 0 . 7s 507 w 11@0000 00o33s w 9ss waaw " 00033 IconVols onsmonitor SL ~ NNeMegoavdievee Transi44t1i1o3n32M3o3n60i0tored 6QuanandEtxamapleiCalcoulatnion thFpUiexvkwceeoaminigechntrwiotnalagestnoimsfooentfhoserfsetpnllaesynntlclocleotnsrpsaeeciaaokmonsisoniavonfeedwwlserreennjtecectpdrabndky wohetihesegtLeoACmmMpoSyiSo.12i.Tn(hoger. ieefillovvinslgoeutseionnss:e)m.Thoresisconcern {wa Soretfr rieqgouesaoifnonnpa1wtiaesspssld)agecrsleteouitemedatbyhletahmaoAnusansntydfpsktwraef)powrnidoggi.npandnarLoebasiedncis Tore `EquatioIn; Analytefound (ppb) =(Anal Pakarea1S peakares)-itocsepid) xIScon. (agin) x DE EonSee roe 130172 - Company Saniized. Donotscontsain TSCA CB) 2H.52D5a50y9:SaRyepeaNteidtDoRsesDerma Toxic A SupplemDeunrtoenm.b1e1r763 Fe ocal l itedo piethtKn v csofely pei E---- toxin, Eestin 2was Bain oi Recovery(%)= fo tos o as wAhne kemcyt cootn00 a a a aoscen taion vin i0sc cse17lwois: spas sic Bg nBSS eoonem)tDD 1 ogD TLma ff=rreiend I Sk NN Domine 2 Soous que From quate --_ Analytefound (pp) = er [(2953-800/341447382] x64.71667x)1 - sets FTromerquation: Bg - 10ppb Neoy:eTls ayilclion vas deosnaigoid br and cis 7.0 EXPERIMENTAL DESIGN Eascghatnablyitikcals(ecewpasefoxraGctReEdRsEcoErEiRng c0o mesrhtosdQSoUENoIeIedceonsdidof a [SE -- `CompanySanitized. Dosnot containTSCA CBI -_-- 28H-D25a5y08S:tuRdyeinpMeleaRteseDedrm-alDTooxicsitey SupplemDeunrtoNnutn1b1e7r63 ---- cocnocneensrafioor,ifed10 vkenoywnG,olcdosnopnreio,ns,oovne flidelsdpsiampleex foified xap own 80RESULTS Touin hecontolrt lasssaps isedinTable. Plasmasampleswat 101% 4.58 iInndTiavbidluealIrLecoTvhereiaevseragepBerBceianttrhecolvaebroireasto+rysftoartnidfiaenddrdsetvipsltisonfsoarm@plEeRs Yarnedetthaeilreadt SItnUdiiSviodouafTl1rheesurpessouflostrst,fhoe6G0hRaelRrpeil-naatthceiroadpsplalamesspmwlaesseaamrpFleiosvaexregieiyvTefunoibcenoTTVam,bsleReTIiLrAtttoohef AR i her: psaspl range from 15.3 gf 026000ng. Awpicalcalibrationcurve tor QE Figures 1.5, end represcatativechromatograms are given in 9CIRCUTHMATSMAYTHAAVEANFFECCTEEDTSHE herar 0know cieatancesthrhaveafectdth uaity ngs of hedia. ~ 100 CONCLUSIONS The atplasmasamplesweresuccessfullyanalyzedsccordingto metho NE 11.0 RETOEFDN ATATANI DSAO MPLNES Wi1hnelybstnioucaolehiflpiponpogaeslrd.rt"seEdpxhtaaeclisltspcciooospgmeepns.leToc,hfiaaylsllldorpcgwiennailkpa,prew5urwdddteestlF,pwaiyeslr5SasmpoeeeibnyacBsoepgygc eofRReey secyh Researecsho'fsearcehivres fbortahecprodcoifvteyspeesepdoin40 CFR.Par793. Reson BeeReseach --_ - Pion Company Sanitized. Doesnot contain TSCA CBI 2285D5a0y9:StuRdeypeinatMeadl-eDoRastesDermal Toxicity _ SupplemDeunpteNnutm1b1e7r63| S-- E -- ~ Bon Research Piso -Y Company Sanitized. Does not contain TSCA CBI 2H6-2-5D5a0y5:StuRdeypeinatMeadl-eDoRastesDermal Toxicity --~ SupplemDenutpNounmtbe11r76|3 -- Table! SummaryoMitog/mL)inRatPlasma Control Samples SpIo"ns)or (-agi_ t) 1#177CCoonnttrrooll 707722223100083 <100 <100 --sw#1C 8 Conotrolm073m 103losi <t<1b o0p0 s -- Ergon Resch ~ - Pe i7072 Company Senitized. Does not contain TSCA CBI 2H-82-5D5a0y9:StuRdeypienatMeadl-eDoRsaetsDermal Toricity SuppleDmuePnotnNtum11b7e6|r3 -- Table. SSuammmplaersyof Recovof eri%e)isn Rat Plasma `SIp"on)sor #17 (LCSA)07722103 (oWgiEmSL 058 Amougnt/Fmor)tified 100 Rec8o)very 0 #616771L65s(MBaytr0ix7S2p2i)s 11202500 #17(LCS 4) 0772308 102 11000000 100 105 110028 066771(8L5os(M8a)toi7xrSzpii0)a 20170000 11000000 #18(LCSA)07/31/03 103 10 18050 108 --#1S8 (LoCS B)T073i 1/03SStQ 7e.t0 Mar0 10t0 iSpeah s7 ) ASVTEORDAEGVE:: 101 as RSD: 45 --_ Evy Resch ~ - Pugs 180172 LampanySanitzec. Doss not contain sc car H2-82-5D5a0y9S:tuRdeypeinstMeadl-eDRoastesDermal Toxicity --~ SupplemDeunPtoNntu-m1b17e6r13 `Table IIT. SSaummpmlaersyof Residue Found forWESMMng/mL) in Rat Plasma E Spo)nsor d rron wriaersieosup rier nmre " eaormioes sarin a7r5 a aswrnmm asass ws assmaaririirnn w4ir awsneaiirmnm wmnn pparaitn 44w aeecearrriiieoesss iiwo 220 ~~ eerriiieson sri 5=0 = aamrwiiiesv 2mn0 ho aarroiineens: i5Poo aarearirisioess 1o0S0 16100 aiaraorieoer Tsoiseo 2500 ccfaoerrrao 1Ta060000 12% --_-- pdioerss WtTehaeon Bryn Rese Page 90872 -- -YY CompanySanltized.Does not contain TSCA cB 2552-D5ay0S9dRy meiepRaesDerama tTosi --~ SupplemDeunPtoNnue1m1b763 ------ TableIV. `ESxutmrmacatreydoRfaRtePsliadsumeaFSoaumnpdlfeosrMESRng/mL)inRe Spo4nsor ries - asgaizn) cacraireiseosup eerier aasss sis ccaarriieess serio 37wss esserrirma errs s1a9z3 3 --st erirserarae4 s --~ Ege Ress ~~ - Pear EompanySaniized. Donotecontsain TSCA cBI 112a55y9S: Rue sDose Dp ematT.oi ~ Suplemfvrai.r oE-- Soh ~~ -_-- neato Lompany Sanitized.Dosnotcontain Tscacal 2H8:-2D55a0y9S:tuRdeypienatMeadl-eDoRsatesDermal Toxicity ~~ SupplemDeuntPoNunmtbe11r76|3 A-- Fa igure 1. Typical Calibration CurveforG -- -- ~ | | 5 i Ey Resar --_ - Paso LompanySaniized.Doesnetcontain TscA car SA 1 oopers s--ea _e--e E---- Er | TETrT e HCli ox 2: | [| Z | 3 3 | 3J | |: | IA opera menn - Sompany Sanitized. Donotecontsain TSCA OBI Eni ts: ti.1. | 28-Day Stu inMdalye Rats Supplement Numbe1r - ------- Figure 3. atogemapres Control Rat Plasma for B= | | | | | |}/ | H | i |3 |3 Ld ee)| tees Re ~~ Lompany Sanitized. Donote contsain TSCA Car A -_-- om SopplomentNumber] S-------- Figured. Ci hromatograM m Reprn esentin5gcC/onntr.oolfRC at Plas-- ma For-- tified rin | 1| 3 | eer. 3 r siti : | | of ee]| ~ =a i | | | | Exygen Research. ~ - Page 250f 72 CompanySanitized.Dossnotcontain TSCA CBI [5DrayeSy-- miehs Figure. VCihrtomSataoggraarmsor fmm SprDui pe ---- RatPlasmaSump for | |; | : || mo Ea: [I | ms rast ~~ Company Sanitized, Does not contain TSCA CBI = --_-- 218.-25D5a0y9:StuRdeye peinatMelde -eDoRsaetDse ermal Tosicty ~ SSpuplplmDemurepnNtoNnuutnm1b1ee7r6r3 ---- Study Protocol DuPont-11763 and Amendments and Deviation _ Lt --. ~ reman Company Sanitized. Does not contain TSCA car $Zo250S9tRyepmeaitedeDomsesDerm Trichy SopplDemuernsoen 1r1763 ~ -- mn Gow we . wan rm --_---- euem | ----m-- a -- : I-------- + ---- : rt ! | : | | mc cot, | | || i ||| i | ; ii| aw emo se se ne se se i i ExypenResearch Page 280f72 --_ - BompanySanitized.Dossnotcontain TscA car 1.2550: RepeatDeedrm-DToosisctey 28-Day Study in Male Rats Dupont11763 Supplement Number 1 --~ -- Ae EN WELL . nom rvs Ee Derr i T401308 CONTENTS i | Ee i i ommoeve : Ps |i RScPuOLNASOTROARNYDCTEoSTFnACeLIsTY =| i! 4 SMTaUADrTYmDetSsNw . oos, | I BAp my i || | D f .AP m PUI i E r Tos-- e n e brmo -- em--e --n-- --er -- --o-- --. i 1. lnC-- hien t -- rer a-- -- y ---- , -- i| K.Tot oe Perm A Lo rin | ~~ |||} M=.A P B;lpHmomenogyoi ---- l A --g -- E, t -- i;i _ RsseTucAoTrmSsTnOARsSomaYv t SaTORs a Ao GET,h | i sf ermmces. e r--i--n-- Tu | ---- TY |! | a || [-- Pesan CompanySanitized.Doesnotcontain TSCA CBI es -- E$2D:82uD5a5S0y9u:SbtuRydeynpienMMatiuel-eeDRRoaseesDsermal Tosicty SSupeppllemmeDenuntpNNoununtbb1ee7r6r3] rm -- WW GM . wan nun ems emapvenon : hetmbt cfmors erpaeree ieds rt i ; cance i:: p hehl meals sie E emsehremT emyE ettE of 250S 0 | ! [ srovsonwe TasTEAGLTY | fToRtypnby iPot e NemskCompt r :Wine oDi.Te | E Tht becr onc Hele Le Ho Bvormensi- i| Eesti, -- ; Ameee RDElGULATtOReYCOcMoPLnIAtNCcE le U82 Tic G0 ct i oe oe ea TL TT Cp Be rep i i | i _-- EEmome wa smn Ey Research more se. wm | Pes00072 --~ - Bompany Sanlized. Doesnot contain TscA car m5 ZD215.y.2D5Sa5ye09Sd:tyaReiypMentaiebdl-eeDRoRsaaesDserm Torii --_ SSuupppllDemmuepmntoNNnuutmm1bb1ee7r6r31 -- An ew ws i tn ens . wi sm . . sora Thsstody design is wefollows: : : i :i tmwza ooo kleonDesaa=i . i| pa | | sS Eoey( a B C TotE ty hi ! EE [A=eSyeoke 2 ay RYme Testdam,7, 14,27 }! ~~ arenassoars ua ! i | oben Th mime ote eoo.e kp ets tLn 1| | || frc S e a uo ism inm e e ee Te enm ii!| } . Bose . ------ -- - CompanySanitized. Doesnotcontain TSCACBI = 21D5..2yD5a5sy0uS9:tduyRyieanMipikeeeDRoaRsaeettDseermd Toi SSwupspllDeemueNpnutomnatbmbe1e1r7r6t31 ~ ---- M[nre r --sa . wa to . nite -- !, SmmrstwebtllnytBotnc(heobrortdp mensa s {| ; TiECovritohob LADa 5 tn. H 0A, n ti i | Aopr iokspknltsoe ny te tnS ybm p keymeme6 ii + Wim to istrhrotedmpcscn, - + SFSondipepmlnttlyodaddfimnpdbm ccrksereeesdifittrsmens | | = | i i S m F id n footsE eln pary ted byimSGom s eneec meeefoe et ppet li oinone 1ii4 PS i|| 0 iry meliiTtanerIDmeh BrtyeBiont i ; I, | Ca| tT ee dtimes--irie mm--ets--on,--in J i | | hcr tea veil tpcmwSinhapintbersysaofddeemiimi f a }i mmo ws sem merme wm sme : Boers pan ~ - Company Sanltized. Does not contain TSCA CBI 25509: RepDeoseaDetcaleTrdici:t. y 28-Day Study in Male Rats Duron 10s Suppl Li 1 ~~ ------ We Ge bE wa nm TT Er Torey intidempsihc tnd hety d ag Bet es eiteDytrss ; pE =t Y aa ee eie e Tra Bee || Began Are dingoyuomc 4sg ctionThebs,rt } i| : Tt A d one r E i iwetcahnR t fteererrE deBlayemE EST oseT e,kbe r T l Ee e ER, | y|| BrSa EE TR Thodayafer thodstdose,spprasimaely0.6-1 i aL.ofblood wascomlleicteedinstoEDTAthes | * Aepmanti Gonn --~ i i This,coAwT evESttyBgBBe et iA---- ee {i tAemeamswea igtht pepl ch lebtdittlgeye, hheiboaStss |{ LC e RSEn re Sn ee ||i j S{2e0idsiyta odyye)w hwioekag ti.Onaye,dEheipe i ivi i i A f7,rrgb we ma t oS -- tBony P- ii; : i _ Penorn -- Company Sanitized. Dossnotcontain TSCA Ct Es 12285D5a0y9:SuRdepyeiantaede-DoRsaeDsermalToxicity SupplemDeunrtoNntu-m1b1e7r65 ~ ------ Ana ew LL wim rv ER stein AdenineSe A2o 8p4p00s i0eHamottsogeypusekr n ricgkynT Triatto o m10rfkoefm ecir hboaSeetmmect ow, A7 amveo ads i 5EmrS ie e i eid,u fedielseortaSvied nmabe lbapt | } rE B Fhewe tdbemneedkoibe essdheppiethoaie ofofLmeda omSeesS covaererdwian lol kdoicee i i or | Comer vTeendmsefec h 5, ir0deTo ameotf t EE SISETAT ! TCTholpgmiepeorvit eiisepci siomteywiSyheiesp.AwnenecaGotarrepirt, carle . |{t i ~ :ii e i f tr n edm aamea i--t--y--HT l--t-- | 5 servi | Tor bw 4 ysdga . Tol stmt tebe 14 . SSSEeE agTtarooidoAdcculrTa rkEiwRemeeEiodaddivtyd-- byimincphge |:i i ee --i Exp Resach Prastorn: ~ Company Sanitzed. Doss notcontain TSCA C1 ---- EE -------------- P BoS ar---- snpee a snzmn ep---- n -- wm stu CER E EAREIp SEEEp t a Esmeere s s SE a E-- E ----T-- b--E ---- e--t EE C CS E EtEeTE eTmCER Re StStINeRERL CCi R EEeon=eStT eaaeaE m sEenai oRmeeEn ! ~ ( SS f i--S E --mS t etE e e E=E E EE E=STEtteE e SraLmEmE e mne !|| EsEEsEteemmmmmm, AteScrstionofthe dyfecesoccapitblogit, ions spiesforslctnd . - are aa. wn sj| psa ove am sm i ~ ompanySanitized.Does notcontain TSCA CBI eer eei efee et 211525a509S:tRyeipneeDRoasaestDeermdal Toy on Deira ~ -- L2G GM RSE 1/13 - oa wT Em ew | t| a I Heder ---- ; A, |! | ! oe odbloodcellconn SE 0d uldsbtionwidth T =ci riE i. me eE e SrmriA.tTtaeen || | Ema Ea ! prothrombintime iene S enti otmr,staw T t er Sf bpet, tfm | cmc | ! a a ---- Emme ee f| --_ i}bo mee ein bop Alkane phosphate ES prion globulin. | | | Hoe cholestersl = HM { ! +p= Tsonllovigsopwlr laeian: 4| [I E V=irbia i -- { Soe eco met siti | {REESE t eresvereeesmeatmeereeeemesmnill i wT a va mm i Eo Rens A ~ EE "EnptnySanitized.Does totcontain TSCACBI o1K4y25o50r5waRemopieaetlDnssesD"e T7 oit csopuepDureonm117-- ~ A------ maporemawesw ee n>un -- -- C -- iites sre : , Etetit ve o tt t e etyi [ S mnRe E i by= col oSiC edea sts An cT ed e ee _ E-rtee ipcT e tre ||! || E E TEa SEEEE: E ~~ | | | | 1 --_--,a -- nesran ~~ EompinySanitized.Doesnot contain Tsca car 12.2555a05:SRynevipeDRosaeesDeslTtoses SplemrenNnumbger rr -- mm, ! nP m er m wed . PY i ! B TE xblop gbeo r"ew 7tt 0 me p he i monda nt i oasttoehe nwtwe | . Dewi Ctoolmes `bodyweightontestday0),orsacifioedbydesign. wliboganpet |i; PE=EenEd = i e=Dmoame t nis |. f==. EC Eorm. Ji || Pa a EE phygland aButagr Misssllmarss. ! i i te --_--a ~ | E=_m-- mR een iee, | || AEmaEreREe EE -- er, |i | AT ssswilbelaced intheappropriateScion, I i [ SumE mihen teiTfet eeeodg Ratssacxifiondbydesignwill ave aSlowingorgsweighed:Ever, kidoeys,adrenal glands, |t |[R E t e ml de ee,Sear || s See mspa c tet ter tigee n oitte !i | | frr o eme tons AR issuescollectedSomrus is he ind contol odfrom ats tha aatnd. :i c-- m-------------- Dreams J rr Company Sanitized. DoesnotcontainTSCA CBI ------------ eee Zo1252D-5uD5ay0yS9SuuyRdieinnMpMaaleeetaRaattssDeerdmaDlTooxisciety swSsuplpleDemmuepenotonNmtu.bm1be1e7r61t3 ~ -- AAmnf iGeanr wse . wi num adie SeS saP me i ET pe Te. | | ;| rR r i totploascsondeem str etybdy myyGTveer, seof gseysrpt ! --~ : | | -_-- moe wm smn Bop Ress i a} mee we ss i P29 -- -_-- EompanySantizee. DassnotcontainTSCACBI 5252.5D5a0y9:SRteimpMyaaletRaesDder-mDTroicsitey SupplemDeuntPoNniu1r763 ~~ ---- Aw nw sa Em stammeaLsures maw nw em !| -- Sigatfcanoewillbejudgedat p <0.5. I ----:---- | ll al ey r------" f I! Weighs |Keon Walls eut| = i |I --EE EEE aes trait -- fer mary frac | 1 amatysisof |KeusalWali1st| - |; StEt SSt LITt eIm ItetLe oTL || E EE eti eE rem te eee serE tenriir caeenr .- Cpt geness,ttarmiBeri metsnt | |[I sBEary wo oussE-- zEG -- |i nd voidpotentialhealth hazards.To voidskiscontact, willbewornwhenbanding. ! ------a i meme wm sen mnme ma com BomRei Peto ~~ CompanySanitized. Does riot contain Tar. cnr a 281.D25a5y09S:uRdeypienatMea-lDeRosaesDermal Torisity SuppleDmuePnotntN1u7mb6e3r ~ CE An Gee Bee f0 ireevyent . wa nw Dowie : [Syyr-------- | AbLyte rt or pnd citctby ps bid i i LeboPfHBeevttbDyeer,e.woiyame,lefrmvepG hnr edf eeesdpHakeb. | |;: 21..OV EERCADTiSCA AiConotC iGboedCA aOPbBncetOr? PSciseta(r1 CiPXd32,9]0,54. sey| i | 3. `TeDoeerdbaSTotxesikBy(GiAUFGe-P19n8H)P.orEesAryo(2i4i)O,OeFofSPoEsSiS,PSiAdL,md i 45.DSp ogeNrX.vce SEtrm,ieT1C9i o4p1eippsSdtADn RovgsiiornA.mrbid feTeil. ain, 262. ~ i}| 6 7. S d SrAo o eRy3i(n.r i5s199)50To.oetAmSeooiffcbneomotetnoCnosreetFs sopkitmcAtisi}s. |i || 5.&SLSeaavsponi,51..8..O114i0,.Rob,VtME7.(059c35i.)StouynmsbodfUeensoicfv.ybeonnntPtloAslrtoyb(iptotnyd | 18So OWoRmdsCa,, eny5.0957.oSet Mod aon, 464md. DIaIsTs,CV.035,AAmbbeesmre ptos iosven ns || 3 1123KDtm,n,0S1W.tE1Lo5t6rd) VeMiol0kaSc58i35.gUktmickoecm o lofvec. 01351. iit | 14FRbeAoU.SdModfrRr Poh, 5 a. fe, i| i _--_-- } mmeme wm ems meme ma eww i Bop Recast san ~~ CompanySanitized.Doesnotcontain TSCACBI --_-- mm - _--m 2H-62-5D5a0y9S: uRepeiantMeadl-eDRoastesDermalToicty SupplemDeunptoNnuti1b1e7r631 ~ -- AER30ctoiwonweentry . naw nw dom 77v0 eusisee ws i i| vied sty Dir orocoL mmo: --Scme--te | !| Sins EreRgres cre i I PeAdt LonBs is A ra,rT e La [0| Aston PtctogyBaten PoF.HRen rege Ii}b ts TeSt Abt [------a Normbe2 rm ;f | trevor oe | | RE ~ fete | ClinicalPathologyEvaluations Decesber23, 2002 } ! SchdiodScifi Decamber23,2002 | | | LS -- i | mma am em meee wm om i Ben Rear Peo --~ CompanySanitized.DoesnotcontainTSCA cay - e mm- r --- 1252-5D5a0y9StRepuensMdtieldy-eDoRsaesDermal Tosi --_ mva arewteewntrem somgiba7in" saunas plemDeunrtanNu1s1b7e6r3 CE wan 1. ; being tieGolgi Ee | || --HepEfaER Bagegh. i | Petclog i | life ugar | | AmiePcie. Pw i hEe EE tsEt cere | | lefatak eps | B - | B | --_-- Bote re tsarn ~ Company Sanitized. Donotscontsain TscA cB: -------------- eee T12o55a09SRyepeatvieDoResDermal Torii pple DupNoan1i76r3 ~ EE [r TT e wa wn , re my , | ProvesAnodeNa | . i |i 1 SD mb70Fy Therote i ened flows (chesSdedy: . otday31 0 tind Finocine ii| ii 2TS aEge,SenctionI L.CClek!tPutT imonyESvyanT I,itaeco I 3meecwN Bltoc.e Reon The i mseda ainrc mig proc. | tangy EE agen | |i m' w gm sm sma ne don i | i !| J ~ -_-- Company Sanitized. Doesnot contain TSCA CE 2S51D1.2y55s0S5o,tdRyyempmedinalteDeorhsrss.Dse0 ms Toric rm OL GM SELL 1/10 sP wpleR nDeonnts um11m7e63r -- oan nm. | -- |-- |AE 1AiAas Plog pies PC.Ma VtPog. oe -- Ltt-- ft fn | yom oh i i I }! i ge = i 1 ER | {! _-- tb --~ i | i a J CawpanySanizeis. Dosnotcontain TSCA CB} D21b25y5Da5sy09wSyuRdimbeiupeDroRessetDsae0 rmta Teoxicdity sSwpekpDwpuerenotenum1te17r6t3 m2s0 omworus a . wan 1 wn ; re ems ! -- [ -- -- y | | EE -------- | :| Tp [ here-- s da-- d e bt,ds | Em pe te I al i i compueed 1 erie i - tla file 3. AH vo | | [J | _-- mmm a cm Bohs more mo. smn ----. ~~ -_-- [Company Sanitized. Doss not contain TSCA CBI H:25509: Eom 28-Day St RepestedDose Dermal are udy in Male Rats. Trichy Duponc11763 sSuuppplleemmenetnNNumubmere|l ia ---- ME2FB0o0trGatmmipwe . nauatiwnm. -; r---- | . rotAt vine Pi bed As pti | Theprotoolsmend slow: { 4JuckaenLaboratory, Decpwasc,NJ,08023" 4 [ Ress:Toid he mesd sof Scion Bioodsty oT | Late lan 3 ity i | | | |i EpaReus i --~ - | 1| i fo. | Ein Seized. ows not contein TSCAGE D21l285Do5a0Sy9u:SbRtenpeiuMantdiMedlc-yeDkosRseassDermalTocky P SSuuppllDemueepnotmnNtoa17bn631 iC --] MBE aM we -- wan nws A -- seem ottAmos | 1e. PoottfAtnt4ben s mim. ! . Heee:rTFeot cdonidnbe TemmcgsinsShebeetefi ; |j EIor RrIt RitsTers -- E-- | | Be:To rm do 6rpgBnd } --~ ; el=e fielles hurd3 || || | B | i --_---- Ee wo vem EpRah i i mre as ewe i Pesto i rm Company Saniized. Does not contain TSCA CBI Te -- 2285-5D0a9y:eStuRdeeypeinatMeadl-eDoRsaetDsermal Toxicity SSpulppelmDeemuenPnNtouNnmutmb1be1e7rr6t3 MEBE tcoometomsutsraa]yoe . new nw -- | i tim | | ; TRo he eofSA peoilsR msewilbopcibtlyipeed pe. ! | Co itt gayts { a i --_ | EE meme wa cm BoaReset i i meme wa em i Pan --_-- Company Sankized. Doss not contain TSCA CBI -- 2H-82-5D5a0y9:StuRdeypeinatMeadl-eDoRsatesDecal Toxicity rr E rr -- m SupplemDeunPtoNnutm1be7r63 ------ nae ; Protos!Amendment 7 ! | |; {EE [vreiLtnpE ,eTtpde--pg--.da--eenm:edPCiYn-- re | :! i Reed esDi,CS ppcGal | rm | | | i [ i == | | |i _--. Ege Recah i | Pesan ~~ -Y Company Sanltized. Does not contain Tse CAI 12.52.5D5a0y8:SuRdyeinpMieleaRatsD.eerdma-lTDoroisi ~ SupplDemuepntonNutm1b1e7r63| { x Exygen.. } i i I ) PN i F[o | [|I { | Po \ Prorteoccoo,lpoeenvaTON = | Out ofOcc STu ILr WTRs: e E en e s pe reA -- re| t| reste I \ --rrm ep ffdFReEdsEDlg, ycoome iiln ,. LA m - Ee \ - !| = \ seis 4 a free sree) sfates \= cremessats : i Xm i NE | Bypass : PgeSio2f ~~ Company Sanitized. Does not contain TSCA OBI -- r-- e ----t A H2-82D5a50y9:StRuedypeiantMeadl-eDoRsaetDsermal Toxicity SuSupppplloemmDeenuntotNnNu.um1mbb7ee6rr3|s ---- Analytical MethodSEEN "Method of Analysis for the Determination of EE Serum by LC/MS/MS" Erp Resch -_-- Pusss20072 Company Sanitized. Does not contain TSCA cay mmm en i | { |i t! b || ~ i| ih \ ms . { Mahoot Anis Denno SU, | \ smn \ \ ElyDior | \\ so, \\ a 5 teahrZT Bm on REE com Tre i |i} | I ESpN Foxconn AmosaTony ||i . so --_ rte n i a "| ad CompanySanitized. Does not contain TSCA CBI S25b255Dy5a0Sy9:SoRydeMpemineiederDosRsestDerm oxic ~. SSpuplelDnueeerroNnaib1e761r3 Yemen] | \ we ! Exygen. ! i ms . v crete rtss ase i | .| \ p---- : i | RT ! oe | ~ | tenw n fR r2o0r ec, mtsm i! | Foo oneomTor SrERsRE i || | Con] | i \ . p Kem ii ED Exygea Research Page S30f72 _ -_-- Company Sanitzed, Dootscontsain Tsc oe s 112559vRee pDoeeDnlt Txt -_-- -- ---- SupplementNumber] i [FS i Bk % on | ! = 7:4 Ad a, hha = | | ~ f i a preci = | | | || J, nts ren] rsa ~ Company Sanitized. Dossnotcontain TSCA CBI 216.2-5D5a0y9:StuRdeypienatMeadl-eDoRsaesDermal Tricity --_ SupplemDeuntPNounmtbe11r763| t | De e`TrOAnFCBOmNLTEeNETnS t., MAGEE SFRGVAL eee] ii ! ii LTf sIATBBOLEARORRFOCmYONAT TSEiNTS--p --------d ----IT--T---- i} ii | E2EEF-- r B-- Ai CM-- O-- UDS -- ---- ------ ---- -- i 32Sean h 53333.,.BPS aenm I STse Fer SA ) S31 SORT TT | | +sa3255m32pCRlS tummmamR e ana SrumR omSt a) as i -- i 34A.2SmS heivmaBami emrasI e ac I TI T IT I II A Bemuemon i}| 5.4q 355333CTNmoOowMrSamSiym nspigI GoiI I TI1} 44. PBA ErTo-- nec C-- onc --o --m ---- IIIT |{ i1 Lo. e5am 4C3,TRhR LUmVwomonLAm mrTAeESTIONS TS i Bogaert Enya Rese i resem | PamSSol 2 TT (Company Sanitized. Donotecontsain TSCA CBI -- TG TT ---- ZD21u82-5SD5ua0y9d:SytuiRdenypeMianatMeedl-ReDaoRstesDsermal Tori SuSuppppllemmeDenuntpioNNnuumtmb1be7er6r31t : LISTORTABLES f Tbe.Rooneyoff Foccsons Meni Sem. __1g i { | LISTOFFIGURES . ) Fpoees1.. lS meensicoe Aso tCrs CMoorneytS tn sn e sten meri Fie.. MR epeeenrreemp map CC 0o7S tSoneceGsRoCoial d | | 1 ! ! I Ps |: ; | i | Sorat Eppes i wie Pssst CompanySanitized. Does not contain TSCA cat tee D12D82yD55aS0y9o:SdtyuRdeiypinenaMtMealde-eDRRoasaesDsecl Toricty - 0SSwppplleemmeDenuntoNnNtuu.mm1b1be7e6r1r3l i 1 sueuey ! Ths pc eilemtdofmle SUM | FRO in cn smbyposi pestotn fn.mite |i EE RndT dR r : Tholowerlz ofquaaistion(LLOQ)forthismethodis10ppbsocQRin QSuitmoi petsingct lionsdssci | TSatnast iy ia ---- JiT R --T To T -- ] i | i P: mt Bose Reet --_ I j san | Peston: Company SanDoiesniotzconieain7d80.A ~ nr bosotae duere7 ssouempe : * Emma couonos ;1 eSsmc RII cesci i i Weg i | . | - "EE | { i ! i -- spats { | ven | rostorn Company Sanitized. Donots contsain TSCA rar B2Ho6-2-5uD5a0y9S:SutuRddyeyipnneMMaaelteeeRRdaet-DsDeromse Toriciy SuSupplpleDemmueePnmtoNnNuutmm1bb1ee7r6r13s i 3. CHEMICALSAND SUPPLIES i . 1. comasus i | SfMeamoaenalO myHGH amdee mSelSwe ne CDOEe OSe ii OE usiso Weg E Bie DBiiE ee vhaoion E i 22 saw a r ==| To | { | Somes Bygen Resch || i rr Passsan BompanySanttized. Does not contain TSCA car - 2He-82-e5D5a0y9S:tRuedpyeiantMeldDeaRsaetsDermal Toxicity ~~ suSpulppelmeemDenuntPtoNNnuutmm1bb1ee7r6r3t ! 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Bort [EN | BaymReseach Pa s00tn2 CompanySanitized.Doesnotcontain Tacs ~m1 T T Tee B2DH6-u2D5ya50yS9:SutRduedypyeiiantnaedMl:eaDoeRsaRetseDermal Toxicity --_ SwSupplpleDemmueepnntoNNnuutmm1b1be7r6e13r ERE es | j 35.Piss SeussLSFoRTEATO Sms !| An1 npmarliycedsnS nda foThs h psppdpsewepfpbet.ncnTE] ti i i 2 { Eo i Cm oeSio rone-T.t heL fine osn d n hswree eresnstM | i i 8SS RpleRkSne EcoInnIt .RaEraiSt ed pkicse seie ; | fTeheehteslesofhe dt ybvid mpm igre I| p-- | ! PGrae utGeao 25ca1Sk01538LoisryotS10ee0d,Coog.ered ~~ i T 0o" ak fr me ed 1 ons ii | 215P20a oP0oprtefosftitoneseQiciinetndod1o0i0ss.a35C.oM8 10olking i !{ [b ynyl D ar Ca, ma w ISLS | ! , Be a Se J 4fpPrea iopiepn's oiandcaS nit5o .pm Hoeo-- SEE a elon : | St370s10amwSh OtoCs NvO tsti i B Br ran resem!i Bigg Resah Preston {ESpany Sanizea.DosswotbontalnTSCA cai -YY H2525D5a0y9:StRuedypienatMede-DRosaesDermal Tosicty -- SupplemDeunptoNnucm1b1e7r631 ii{! oE mmnTsao RhkReT R eE e nf Sionallfocifcaonstandardsolutions a 8religeeatr(in125-6 LDPE !||! e 3oD5nr3ci.oCinotndte eetnSeinddnerosfE hreldoe fn hFcSiRnpie, i ! i C=oMncr.nOF SR Foribouion soVSmael)EmeoTf COGEoioRe.noEf . 1 ||i ooaaaE onr ET2m F0wIofuaorr 20 om | L r---- oven | i CI J -- |i 4 METHOD T4imoowvdabguaof 8 td i given iow,fledby 4ete ii | desciptiM onofeachsepo .NetoeBCon upinlea s) i ! La Pos T nt ie i | | Lona+ mums 1 | { prp-- Noserinsefo rn pis. 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Boos notcontin Tar - EgpanySanies.Doesmo contin TSCA O81 LLEe:SStoeettat ety ~ Dpiere | E--RE--Hor eeemt j i Mobile Phase = in | FT O=oE o%p jwm =nz | 1 5000 8 @ { i ipiIos: BB a 0 100 05 ~ ;( E E-- oeyree=uLaEE oFErtsEa tmEism 2 F 08R apEmE dieem8a ||; Ee RmaLn! | Iterpened trvughoct the may rn. i | i ote astamive LMSIMS symmaybosndcocedemonsnied 0be | Cl T bg eana | o Renmei s| S3EemmSnosoneenI sees a ne fl.Thistn ith weddg route matys SE --C; -oEr --rr |:|| 453. CallbrationProcedures i CompanySanitized, Does not contain TSCA CRI 1L425n565:TRaepDermTiot --_ sDus rr1765 ji|| m SfEEEEromEEerimb ene Em,hmaaro e semamenvss i ay be exclodedfromtheclient curve. However, hetolnumberof ;. SDEaRErsEEESETTRE me TER 1 Deelle () tocateuionces raced mtbo v RIAL prESTrRm, feo i yer Ee SttNesep me | ~ i f momr smmri. ||! i l| oa SEE EEEmEyEaSrEmEeaTTEm ERSTEILS TRE S, , i LL Ancat setofcalibnsonsandacdsshoskdbeinjectedatthe ofa t Sabcuion adi maybeinchoded atebeginningwd 2teendof5. Te ni xsec mtem | necessary, Gliathe samplesin sceooitile13 give &responsewithinte. J bo Po0rLifLiOcQai)oanrroeccoovnesriideesrfedulsiencegwpriatbhlie.n85t 115% 0 - 120%fox Jovelsat o I i S= omSaRtmtiisEeEi Lcpu ! 2Stipes whichnop reected(0, ga sone shues I Srv men I Someta -- ~ Company Sanhized, Does not contain Tsca ray E255e0.rReipseo!sDorm sity --- sop -- : } B El E mt e onsis i if{ 4E -6--AcGG cT arrulncsCairE esE E .ees: cer?E e" ce. !| i f E E EErymC g E emE ri e re ten retest 2Anyanalytepresentinmethodbak siboa eat 5.60 = owe then . |i | SEEECEERNER --_ |i; EhP T o EatinSar E fti eersifsrtict E cetl by ogmgm |i | E fe mme LL mma | { er ---- ; | sopropeat vegetokbe taken to aos sree opeason id | SJ Eso EBmammmermee The ciltriasatbepexfocmed as aystem suitability es,before | | EBS E Ex E t cotncR en cn cornI at sas meE im nogg | ! re somata wn | notions ~ -_-- `Company Sanitized. 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