Document ymjXGv39dbngxDLY26BDv54a2

" el CT EEomm Toy 2083W31s AR226-0566 PretHAG TCX111 Study Title Oral (Gavage) Pharmacokinetic Recovery Study of PFOS in Rats PROTOCOL. Author Lisa Clemen Date: - June 8, 1999 Performing Laboratory 3M Environmental Technology & Safety Services 3M Environmental Laboratory 935 Bush Avenue St. Paul, MN 55106 Laboratory Project Identification FACT-TOX-111 U2994 : ti SM EmvionmontlLars 609a52 Pago 1110 . Protocol #FACT-TOX-111 Study Identification Oral (Gavage) Pharmacokinetic Recovery Study of PFOS in Rats Test Material Sponsor Sponsor Representative Perfluorooctane sulfonic acid potassium salt (T-6295) 3M Toxicology Services - Medical Department 3M Center, Building 220-2E-02 St. Paul, MN 55144-1000 Marvin T. Case, D.V.M,, Ph.D. 3M Toxicology Services Telephone: 651-733-5180 Facsimile: 651-733-1773 Study Director : Kristen J. Hansen, Ph.D. 3M Environmental Technology and Safety Services Building 2-3E-09 651-778-6018 Study Location(s) In vivo Testing Facility Analytical Testing Laboratory Argus Research Laboratories, Inc. 905 Sheehy Drive, Building A `Horsham, PA 19044 3M Environmental Laboratory `Building 2-3E-09 935 Bush Avenue St. Paul, MN 55106 SERSE8 s sre IM EnvironmentalLaborstory 060953 Page 20110 . `Sub-Contract Laboratories Proposed Study Timetable S`Sttuuddyy ICnoimtipalteiotnioDnatDeate. Protocol #FACT-TOX-111 Advanced Bioanalytical Services, Inc. 15 Catherwood Road Ithaca, NY 14850 Battelle Memorial Institute 505 King Avenue Columbus Ohio 43201-2693 June 8, 1999 August 8, 2000 1. Sruoy Oral (gavage) pharmacokinetic recovery studyofpotassium perfluorooctane sulfonic acid (PFOS) in rats. 2. Purpose T(hPiFsOSan)aliyntiscpaelcistmuednysoisfdleisviergnaenddtsoedreutmeorfmirnaetsl.evTehlseoifnp-oltfaespsoirtuimopneorfftlhuiosrosotcutdaynewsauslfcoonnadtuected aatnAarlygzuesdRaetsAedavracnhcLeadboBriaotaonraileyst,isctauldSyer#v4i1c8e-s0,15I.nc.Alalndsealrlulmivsearmspalmepslweisllexbteraecxtterdacatnedd aannadlyzed at BLaatbtoerlalteoMreymaosrimaetlhIondstsitaurtee.deAvdedliotpieodnaalnadnvaallyisdeastemd.a.y Ibfe apdedriftioornmaeldaantalthyese3s MarEenpveirrfoonrmmeendtaaln amendment to this protocol will be written. 3. REGULATORY COMPLIANCE "ATdhmiisnsitsutrdaytwiiolnl,bGeocoodndLuacbtoerdationrayccProarcdtainccees wSitatnhdtahredsU,niFtineadlSRtuatlees2F1ooCdFaRn5d8D,rwuigth the exception twhialtl annoatlbyseicsoofntduhcetetde,stamnadteirsitahlemriexstpuornseibfiorlictoynocfetnhtreatSipoonn,ssoorl.ubility, homogeneity, and stability SENS" RE [2S Z[F8 4. QUALITY ASSURANCE Tsthuedy3cMonEdnuvcitr,odnamtean,taanldLfaibnoalrarteoprorytQtuoaldiettyerAmsisnueracnocmeplUinaintcweilwlitrhevGioeowdthLeabporortaotcoorly aPnradcatuidciet Standards and with 3M Environmental Laboratory Standard Operating Procedures. The QA Unt at the sub-contract laboratory will audit ther study conduct, data, and results report prior to submitting to the 3M Environmental Laboratory. 60954 IM Environmental Laboratory Page 30 10 . Protocol HFACT-TOX-111 5. TEST MATERIAL 5.1 Refer to Argus Research Laboratory protocol for study #418-015. 6. CONTROL MATRICES 6.1 IdentificationRatliver and serum, will be recorded in the raw data and and/or rabbit liver and serum included in the final report traceability numbers 6.2 Source Argus Research and/or Sigma Chemical 6.3 Physical Description Rat liver and serum, and/or rabbit liver and serum 6.4 Purity and Stability Not applicable 6.5 Storage Conditions Frozenat -20 C+10Cor-50C+10C 6.6 Reserve Matrix A portionofthe control matrix will be retained in the 3M archives for as years long as the quality of following the effective the preparation affords evaluation, but not dateof the final test rule (ifapplicable). longer than ten verification. 6.7 Dispositi regulation. on Matrices will be retain Certain matrices (feces, ed at the 3M Environmental urine, and blood) may be Laborato disposed ry per after GLP QAU 6.8 Safety Precautions Refer to MSDS for chemicals laboratory attire, and follow adequate precautions for used. Wear appropriate handling biological materials and `preparing samples for analysis. 7. REFERENCE MATERIAL 7.1 I(deqeunitviafliecnattliootns) Potassium perfluorooctanesulfonate (PFOS), lot #s 171, 215, or 217 7.2 Source 3M Specialty Chemicals LE 5] 2 of 2 gas g 7.3 Physical Description White powder 7.4 dPeutreirtmyinaend.d Stability Purity of PFOS is 99% or greater. Stability has not been 7.5 Storage Conditions Room temperature 7.6 RbeesreetravineedMaastelroinaglasAthreesqeuravleitsyaomfpltheefprroempaeraacthiobnaatfcfhorodfsPeFvOalSuautsieondi,nbtuhtinsotstluodnygewrill than ten years following the effective dateo. fthe final test rule(if applicable). 7.7 Disposition Unused reference material will be retained for use by the 3M `Environmental Laboratory and will be discarded when the qualityof preparation no longer affords evaluation. 060955 IM EnvironmentalLabarstory Page 40110 Protocol #FACT-TOX-A11 7.8 Safety PrecautionsRefer to MSDS for chemicals used. Wear appropriate laboratory attire, and follow adequate precautions for `handling biological materials and `preparing samples for analysis. 8. TEST SYSTEM `Rats wereusedas the test system and were maintainedanddosed as. described in Argus Research protocol beginnin #418-015. g 42 daysp The female rats will be given the rior to cohabitation until day 0 of test material or control once da presumed gestation. See table il 1 y for more dosage information. Table 1 Dosage Levels, Concentration, and Volumes Dosage Number of Dosage Concentration | Dosage volume. Group female rats mg mg/kg/day fo mg/kg/day fo mL/kg Us| F G z fjeoer s jJooem.TfF s || ED 1b kh 4/2249 9. SPECIMEN AND SAMPLE RECEIPT The 3M Environmental Laboratory will receive homogeneity samples and specimens ofthe following body tissues and fluids from the indicated points in the study. All specimens will be packed on dry ice for shipping. See table 2 for more specimen information. Body tissue/fluid Table 2 Specimen Information Collected Expected # of specimens Se --Dr amau ndPm up animals Urine and Fec--eDasm and Pup animals Tiv--Dearm and Pup animals Dam-Predose, Days 7, 14, 15,21, | 144 Dam and 22 Pup-Day 21 : - 24 Pup (pooled) Predose, Days 7, 15, 21, and 22 sDtaumd-yAt the terminationofthe Pup-Day21 120 Urine and 120 Feces 24 Dam 24 Pup (pooled) #4 RE Total numberof expected specimens: 456 | Total numberof test animals: 16 2 Total number of control animals: 8 060956 3M Environmental Laboratory Page 50 10 Protocol HEACT-TOX-111 Specimens sent to 3M Environmental Laboratories will be received and tracked according to applicable Standard Operating Procedures. 10. PREPARATORYMETHODS 10.1 FFlAuCoTrMoc-h1e.mi1c,alExSturrafcatcitoannotfPfortoamsLsiiveurmfPoerrAfnlauloyrsooicstUasneisnuglfHoPnLaCt-eEolrecOtthreorspArnaiyo/nMiacss Spectrometry 10.2 FElTuSo-r8o-c4h.e1r,niEcxatlraCcotimopnooufnPdostafsrsoimumSePreurfmluoorrOotohcetranFelsuuildfofnoartAenoarlyOstihserUsing HPLCElectrospray/Mass Spectrometry 10.3 pIfroptroecpoalrawtiolrybmeewtrhiottdesn.othAenrytdheavnitahtoisoenslifsrteodmatbhoevsee mareethuosedds,wainllabmeenddocmuemnetnttoetdhiasnd included with the study data. 10.4 Iifnacnlauldyestehseiarrmeestuhbocdosntarnadctceodpiteosootfheeraclahbomreatthoroidesw,ilalnbaemaetntdamcheendttowitlhlisbeprwortiotctoeln.to 11. ANALYTICAL METHODS 11.1 FACT-M-2.1, AnalysisofFluorochemicals in Liver Extracts Using HPLCElectrospray/Mass Spectrometry 11.2 EinTSS-e8r-u5.m1o,rAOntahleyrsiFsloufidPEoxttarsascitsumUsPeirnfgluHoPrLoCo-cEtlaneecsturlofsopnrataey/oMraOstsheSrpeFclturoormoecthreymicals 11.3 pIrfoatnoaclyotliwcailllmbeethworidtsteont.heArntyhadnetvhiaotsieolnisstferdoambothveesearmeeutsheodd,sanwiallmebneddmoecnutmetnottehidsand included with the study data. 11.4 Iifnacnlauldyestehseiarrmeestuhbo-cdosnatrnadctceodpiteosootfhcearclhabmoreatthoroidesw,ilalnbaemaetntdamcheendttwotihllisbeprwortiotctoeln. to sR Ne shesxe 12. DATA QUALITY OBJECTIVES Tinhdeicnautomrbsearreofinscpliukedse/dduipnltihceataensa,lyutsiecaolfmseutrhroodgsa.tes,Inanadddiitnifoonr,mtahteiofnololnowoitnhgercrdiatteariqauwailliltybe met: 12.1 Linearity #2098 122 Limits of detection/ quantitation 12.2.1 Method Detection Limit (MDL) for PFOS a) Sem: L75ppb b) Liver: 15ppb 00957 3M Environmental Laboratory Page 601 10 Protocol #FACT-TOX-111 12.2.2 Limit of Quantitation (LOQ) -- Equal to the lowest acceptable standard in the calibration curve 12.3 Duplicate acceptable precision < 30% for the method 12.4 Spike acceptable recoveries 70% - 130% 12.5 cUosnefiromfactoornyfimretmhaotdo.ryImfaectohnofidrsmatIonrdyetmeertmhinoadtiessuasmepdl,easnwailmlebnedmree-natnatloytzheids using a protocol wil be written. 12.6 Demonstration of specificity Chromatographic retention time, mass spectral daughter ion characterization. 13..5UB-CONTRACTED ANALYSIS 13.1 All analyses as detailed in this protocol will be performed at 3M Environmental Laboratories, Building 2-3E-09, 935 Bush Avenue, St. Paul, MN 55106, at Advanced `Bioanalytical Services, Inc., 15 Catherwood Road, Ithaca, NY 14850, or at Battelle `Memorial Institute, 505King Avenue, Columbus, Ohio 43201-2693. 13.2 An amendment to this protocol will be wriit f at naleysn es are performed at laboratories other than the 3M Environmental Laboratories, Advanced Bioanalytical Services, Inc., or Battelle Memorial Institute. 14. STATISTICAL ANALYSIS Averages and standard deviations will be calculated. `The statistical methods that will be used are. described below: 14.1 Data transformations and analysis Data will be reported as the concentration (weight/weight or weight/vol)of PFOS or `metabolite per tissue or fluid. 14.2 Statistical analysis Statistics used may include regression analysis. of cwointcheinnteraatcihodnossoevegrrotupi.meI, fanndecsetsasnadrayr,dsdiemvpilaetisotnatsisctailccaulltaetsetsd, fsourcthheascoSntcuednetnrta'tsitontsest, may be applied to evaluate statistical difference. 15.RePORT oo IS EIS A report containing all Laboratory. If analyses the are resultsofthe study will sub-contracted to other be prepared laboratories, by the 3M Environmental each laboratory will prepare a TLaPboRrataonrdysruebpmoirtt.itEtaocthhere3poMrtEwnivlilroinncmleundtea,lbuLtanbootrabteorlyimfiotreidntcol,usthieonfionltlhowein3gM,Ewnhviernonmental applicable: E151 Name and addressofthe facility performing the study $$ 15.2 Dates upon which the study was initiated and completed 00953 IM Environmental Laboratory Page 701 10 Protocol #FACT-TOX-111 15.3 A statementofcompliance by the Study Director addressing any exceptions to Good Laboratory Practice Standards 15.4 Objectives and procedures as stated in the approved protocol, including any changes in the original protocol 15.5 Tsthreentgetsht,spuubrsittya,ncaendidcenotmipfoiscaittiioonnboyrnoatmheer,acphpermoipcraialtaebschtarraaccttserniusmtibcesr, iofrpcroodveidneudmbbeyr, the Sponsor 15.6 Stability and the solubilityofthe test substances under the conditions of administration, if provided by the Sponsor 15.7 A descriptionofthe methods used to conduct the test(s) 15.8 A description ofthe test system 15.9 A descriptionofany circumstances that may have affected the quality or the integrity ofthe data 15.10 The nameofthe Study Director and the namesofother scientists, professionals, and supervisory personnel involved in the study 15.11 dAatdae,scarsiputmimonaorfythanedtarnaanlsyfsoirsmoafttiohnes,ancaallyctuilcaatliocnhse,moirstorpeyrdaattiao,nasnpderafsotramteedmeonntotfhethe conclusions drawn from the analyses 15.12 Statistical methods used to evaluate the data,ifapplicable 15.13 The signed and dated reportsofeach of the individual scientists or other professionals involved in the study,ifapplicable 15.14 The location where raw data and the final report are to be stored 15.15 AinsspteactteimoennstapnrdepaaurdietdsbwyetrheemQaudael,itaynAdstshueradantceesUonfitanlyisftiinngditnhgesdraetpeosrttheadttsotuthdey Study Director and Management IcfhiatnigsensewcielslsabreymtaodmeakinetchoerrfeocrtmioonfsaonraamddeintdiomnesnttoiasrseupeodrbtyaftheerSitthuadsybDeireenctaocrc.epTtheed, the amendment will clearly identify the part of the report that is being amended, the reasonsforthe amendment, andwill be signed by the Study Director. Eg| g EINE" S SP5e2 16.LOCATION OF RaW DATA, RECORDS, AND FINAL REPORT Original data, or copies thereof, will be available at the 3M Environmental Laboratory to tfahceilfiitnaatle raeupdoirtts iosfctohmeplsettueddy,daulrlionrgigitisnaplropgarpeesrsdaantad,bienfcolruediancgcetphtoasneceiotfetmshelisftiendalberelpoowr,t.wiWlhlebne breytariengeudlaitniotnh,eaanrdchsisveessotfabl3iMsheEdnvbiyro3nMmeEnntvailroLanbmoernattaolrLyfaobroaratolreaystStapnedrairoddoOfpteriamteinags specified Procedures 00959 3M Environmental Laboratory Page 8 of 10 . Protocol #FACT-TOX-111 16.1 Tsthuedyf/oplrloojweicntgarrcahwivdeastaacacnodrdriecnogrtdos will be retained in 3M Environmental tLhaebostruadtyorfyolSdtearnidnatrhdeOperating Procedures: 16.1.1 Approved protocol and amendments 16.1.2 Study correspondence 16.1.3 Shipping records 16.1.4 Raw daa 16.1.5 Approved final report (original signed copy) 16.1.6 Electronic copies of data 16.2 Tthheeafroclhlivoewsinagccsourppdoirntgitnog3reMcoErndvsiwriolnlmbeentraeltaLianbedorsaetpoarryatSetlaynfdraormd tOhpeersattuidnygfolder in Procedures: 16.2.1 Training records 16.2.2 Calibration records 16.2.3 Instrument maintenance logs 16.2.4 Standard Operating Procedures, Equipment Procedures, and Methods 17. SPECIMEN RETENTION ``pSepreicoidmoefnsimwiellasbespmeaciinftieadinbeydirnegtuhleat3ioMn EornvaisrloonnmgenatsatlheLaqbuaolriattyoorfytshpeepcriempeanraatricohnivaefsffoorrdsa eapvpalliucaatbiloen),,bauntdnoats lesotnagbelristhheadn btyen3yMearEsnvfiorlolnomwienngtatlheLeafbfoercattioverydaStteaonfdtahrdeOfpinearlatteisntgruPlreoc(eifdures. 18. PROTOCOL AMENDMENTS AND DEVIATIONS PDilraencnteodrcahnadngtheesStpootnhseorp'rostRoecporleswielnltabteivien.thAemefonrdmmeofntwsriwtitleln baemecnondsmiednetrsedsaisgnpeadrtboyftthheeStudy ipnrtohtoecoflinaalndrewpiolrtl.bAenayttoatchheerd cthoatnhgeefsinwailllprboetoicnolt.heAlflorcmhoafngwersitttoetnhedpervioattoicoonls,wsililgnbeedibnyditchaeted Study Director and filed with the raw data 19. ATTACHMENTS _|.T 19.1 Attachment A Preparatory and analytical methods l R: #58Ss g 3M Environmental Laboratory e360 Page gol 10 PTT 20. SIGNATURES Mewes 7G in T. Case, D.V.M., Ph.D., Sponsor Representative 7fungore Date A -- tenJ. Hansen, Ph.D., 3M Environmental Laboratory Study Director ~ Date n5N 28 3 hf2 i Enonmena Lay 00961 Seon seers - Study Title Oral (Gavage) Pharmacokinetic Recovery Studyof PFOS in Rats. PROTOCOL AMENDMENT NO. 1 Amendment Date: August 12, 1999 Performing Laboratory 3M Environmental Technology & Safety Services 3M Environmental Laboratory 935 Bush Avenue St. Paul, MN 55106 5: $ # S sss g Laboratory Project Identification ET&SS FACT-TOX111 LIRN U299%4 3M Environmental Laboratory CCessz Protoc`oAlmFeAnCdTm-enTtOXN1o.111 This amendment modifies the following portion(s) of the protocol: 1. PROTOCOL READS: Section 10.0 and 11.0 list the following methods to use for extraction and analysis: FFlAuCoTr-oMch-e1m.i1cal"ESxutrrfaaccttiaonntoffrPoomtLaisvseirumfoPreArnfalluyorsoioscUtsaniensgulHfPoLnCa-tEeloerctOrthoesrprAanyi/oMnaiscs Spectrometry" FACT-M-2.1 "Analysisof Fluorochemicals in Liver Extracts Using HPLC-Electrospray/Mass Spectrometry" AMENDTO READ: Theextractionand analytical methods FACT-M-1.1 and FACT-M-2.1, respectively, were updated on 07/22/99 to: ECToSm-p8o-u6n.0ds"EfxrtormacLtiivoenorffoProAtnaaslsyisuims PUesrifnlguoHrPoLoCct-aEnleescutlrfoonsaptreaoyr/MOatshserSpFelcutorroomcehtermyi"cal 'CEoTmS-p8o-u7n.0ds"AinnaLliyvseirs EoxftrPaocttasssUisuimngPeHrPfLlCuo-rEoloeccttarnoessuplrfaoyn/aMtaesosrSOptehcetrroFmleutorryo"chemical RweErAeSuOpNd:atTehdeoenxt0r7a/c2t2i/on99antod EaTnaSl-y8t-i6c.al0 maentdhEoTdSs-8F-A7C.T0-.M-ThLe.s1eamnedthFoAdCsT-wMe-re2.u1p,darteesdpetcotirveepllya,ce tethheeer)x,trPacOtAioAn saonldveMnotneotehsytlearcewteartee wrietmhoaveddiffferroemnttehxetsrtacatnidoanrdsomlivxe,ntanMdTMB5E56(mweatshyalddteerdttbouttyhle standard mix. The analytical method was updated to include linear regression with 1/x weighting and a few minor changes in the HPLC 1100 instrument parameters. S| Ei IS 35: 2. PotRhOerTOlaCbOorLatRoEriAeDsSa:nSaemcetniodnme1n0.t4wainlldb1e1.w4ristttateen tthoaitnicfltuhdeeatnhaelsyesmesetahroedssu.b-contracted to AMEND TO READ: The extraction and analytical methods to follow at Advanced Bioanalytical Services will be attachedto the protocol. The extraction and analytical method to follow at Battelle Memorial Institute is: "Method for Analysisof Perfluorooctane Sulfonate (PFOS) in Rat Sera-by LC/MS/MS, Version}io Oliv Reason: The analytical methods at the sub-contract laboratorieswere not included in the original protocol. 0 @ue alg bw 9127199 060963 IM Environmental Laboratory ProtocTorloFrAimCerTtInOoN1 3. PROTOCOL READS: Section 12.2.1 b) lists liver method detection limit as 15 ppb. AMEND TO READ: The liver method detection limit is 8.50 ppb (ng/g). REASON: The validation supporting methods ETS-8-6.0 and ETS-8-7.0 included a lower `method detection limit for PFOS. Amendment Approval Manes TG in Case, D.V.M., Ph.D., Sponsor Representative (Qhosg ud1995 Date Kris J. Hansen, Ph.D., Study Director Datt Ny BRE #= 3M Environmental Laboratory 00964 Study Title Oral (Gavage) Pharmacokinetic Recovery Study ofPFOS in Rats PROTOCOL AMENDMENT NO. 2 Amendment Date: September 30, 1999 Performing Laboratory 3M Environmental Technology& Safety Services 3M Environmental Laboratory 935 Bush Avenue St. Paul, MN 55106 aE Laboratory Project Identification ET&SS FACT-TOX111 LIRN U2994 gk T=i 3M Environmental Laboratory : 10965 Protoc`oAlmFeAnCdTm-eTntOXN1o.112 This amendment modifies the following portion(s) of the protocol: 1. PROTOCOL READS: pSeercftliuoonr2ooscttaatneesstuhlefosntautdey(isPFdOesSi)gninedsptoecdiemteenrsmionfellievverelasondfspeortaasinsirautms. AMEND TO READ: `The study is designed to determine levels ofpotassium perfluorooctanesulfonate (PFOS) in specimens of liver, sera, and urine in rats. Reason: The urine analytical methods were validated and approved after approvalofthe original protocol. . be 1Re Ss fs g 2. PROTOCOL READS: Section 10.0 and 11.0 list the following methods to use for extraction and analysis: ETS-8-4.1 "ExtractionofPotassium Perfluorooctanesulfonate or Other Fluorochemical CEToSm-p8o-u6n.0ds"EfxrtoramcStieornuomffPoortAansasliyusmisPeUrsfilnugorHoPoLctCa-nEelseucltfronoastperaoyr/OMtahsesr SFpleucotrroocmheetmriyc"al Compounds from Liver for Analysis Using HPLC-Electrospray/Mass Spectrometry" C[EoTmSp-8o-u5n.1ds"AinnaSlyesriusmofExPtortacatsssiUusminPgerHfPlLuCor-oEolcetcatnreosuslpfroanya/tMeaosrsOStpheecrtFrloumoertorcyh"emical - ETS-8-7.0 "Analysisof Potassium Perfluorooctanesulfonate or Other Fluorochemical Compounds in Liver Extracts Using HPLC-Electrospray/Mass Spectrometry" AMEND TO READ:: ETS-8-4.1 "ExtractionofPotassium Perfluorooctanesulfonate or Other Fluorochemical CEToSm-p8o-u6.n0ds"EfxrtormacSteiornuomffPoortAansasliyusmisPeUrsfilnugorHoPoLctCa-nEelseucltfronoastperaoyr/OMtahsesr SFpleucotrroocmheetmriyc"al Compounds from Liver for Analysis Using HPLC-Electrospray/Mass Spectrometry" [CEoTmSp-8o-u9n6d.0s "fErxotmraUcrtiinoen ofofrPAontaalsyssiiusmUPseirnfgluHoPrLooCc-tEalneecsturlfoosnpartaeyo/rMaOstsheSrpeFclturoormocehtermyi/cMaalss Spectrometry" [ETS-8-5.1 "Analysisof Potassium Perfluorooctanesulfonate or Other Fluorochemical Compounds in Serum Extracts Using HPLC-Electrospray/Mass Spectrometry" [CEoTmSp-8o-u7n.0ds"AinnaLliyvseirsoEfxtProacttasssUisuimngPeHrPfLlCu-oEroloeccttarnoessuplrfaoyn/aMtaesosrSOptehcetrroFmleutorryo"chemical [ETS-8-97.0 "Analysis of Potassium Perfluorooctanesulfonate or Other Fluorochemical Compounds in Urine Extracts Using HPLC-Electrospray/Mass Spectrometry/Mass Spectrometry" "REASON: The extraction and analytical methods ETS-8-96.0 and ETS-8-97.0, were approved. after approvalof the original protocol. 60966 3M Environmental Laboratory Protoc`oAlmFeAnCdTm-eTntOXN1o.112 3. PSeRcOtTioOnC6O.L1 RliEstAsDcSo:ntrol matrices as rat liver and serum or rabbit liver and serum. Source Argus and/or Sigma Chemical. AaCnoMdnE/torNroDlraTmtaOutrRriiEnceAe.Ds:SidoeunrtcifeicAartgiuosn,rSatiigvmearCahnedmiscearlu,m,LarambpbiirteliBvieorlaognidcaslesr,umB,iohluogmiacnaluSrpienceialty Corp. and/or Golden West Biologicals. RAEdAdiStOiNon:ofcontrol urinBs specifications. 4. SPeRcOtiToOnC1O2L.2R.1EAaD)Sli:sts sera method detectionlimitas 1.75 ppb and b) lists iver method detection limit as 15 ppb. AThMeEmNeDthToOdRdEeAtDe:ction limits for all compounds and matrices will be taken from the methods used for extraction and analysis. TRSthEaeAtSmeOmeeNtnh:todwadsetaedcdtieodntloiamiltlsowlifstoerdasrube-scpoenctirfaicctetdo atnhael3ysMesEnavndi/roornmreenvitsaeldLmaebtohroadtsor.y. =|RR g oBft Eo g 3M EnvironmentalLaboratory 400099687 ProtocAomleFnAdCmTe-nTtOXN1o.112 5. PROTOCOL READS: Section 16 states that the original data, or copies thereof,willbe available at the 3M EancvceiprtoannmceenotfatlhLeabfoinraaltroerpyortto. fWachileintatteheaufdiintaslorfetphoret sits ucdoympdluertiendg,itasllproorgigriensasl apnadpebrefdoartea., idantcal,udaipnpgr:oavpepdrfoivneald rperpootrotc,oelleacntdroanmiecncdompeinetsos,fdsattuad,ytrcaoirnriensgproencdoerndcse,, csahliipbpriatnigonrerceocrodrsd,s,raw. instrument maintenance logs and standard operating procedures, equipment procedures, and `methods will be retained in the archivesofthe 3M Environmental Laboratory. ASeMcEtiNoDn T16O sRtEaAteDs:that the original data, or copies thereof, will be available at the 3M aEcncveiprtoannmceentofatlhLeabfoinraaltrorpyortto.fWachileintatteheaufdiintasl orefptohretsistucdoympdluertiendg,itasllproroiggriensaslapnadpbeerfdoartea, diantcal,udaipnpgr:oavpepdrfoivneadl rperpootrotc,oalnadndelaecmternodnimcenctopsi,essotufddyactoarwrielslpboendreentcaei,nesdhiipnptihnegarrecchoirvdess,orfaw . tihnest3rMumeEnntvimraoinnmteenntaanlceLalboogsr,atsotrayn.daArldlocpoerrrateisnpgonpdrioncgedturraeisn,inegqrueicpomrdesn,tcparloicberdatuiroens,reacnodrds, `methods will be retained in the archivesofthe facility performing cach analysis. REASON: Clarificationofthe dispositionofarchived records ifanalyses are performed ata subs contract laboratory. 6. PROTOCOL READS: Section 17 states that specimens will be maintained in the 3M Environmental Laboratory specimen archives. AMEND TO READ: `Specimens wil be maintained in the 3M Environmental Laboratory specimen archives. All SLapbeocriamteonrsysuepntontocsoumbp-lceotnitoranoctfalanbaolryastiosriaensdwislulbbmeisrseitounronfetdhteo tshueb-3cMontErnavcitrolanbmoernattaolry(s) foirniaglinraelpocrhta.inTohfecussptecoidmyenasndwirlelcobredrsoeftsutmoerdawgiethcotnhdeitfioolnlsowwihnigledoactutmheenstuabt-icoonn:trtahcet fsaicginlietdy. REASON: Clarificationof the dispositionofspecimens and documentation for analyses performed by a sub-contract laboratory. 2 Bd5 3M Environmental Laboratory Ce3G8 Amendment Approval Protoc"olAmFeAnCdTm-enTtOXNo1.112 I/O Marvin Case, D.V.M., Ph.D., Sponsor Representative Lhe bh Kristen J. Hansen, Ph.D., Study Director Date' 5 out 1799 Date RE Eg 53 3M Environmental Laboratory 00969 : v Study Title Analytical Laboratory Report on the Determinationofthe Presence and Concentration of Potassium Perfluorooctanesulfonate (CAS Number 2759-39-3) in the Serum, Liver, and Urine of Crl:CDBR VAF/Plus Rats Exposed to PFOS Via Gavage PROTOCOL AMENDMENT NO. 3 Amendment Date: 20 January 2000 sEh RE ] s PeS 2 3M EnviroUnrmiennetaAlnTaleycsheosology and SFalfueotryinSeerAnvailcyetsical Chemistry Team B9u3i5ldBiunsgh2A3v6e-n0u9e St Paul, MN 55106 Performing Laboratories PerforLmiivnergALnaalbyosresatories B5a0t5teKlliengMeAmvoerniuea.l Insitute Columbus, OH 43201-2693 AdvancedSBeiroaunmalAyntaiclaylseSesrvices, I1n5c.Catherwood Road Ihaca, NY 14850 Laboratory Project Identification ET&SS LRN-U2994 FACT TOX-111 Argus Study: 418-015 3M Medical Department Study: T-6295.14 `3M Environmental Laboratory 00970 APmreontdocmoelntLRNNu-mU2b9e93r4 This amendment modifies the following portion(s) of the protocol: 1. PROTOCOL The study READS: director for the present study was identified in the protocol as Kristen J. Hansen, Ph.D. AMEND TO READ: The role of study director for the present study was reassigned to Marvin T. Case, DH.aVn.sMe.n,,Phh.aDs.,beaesnofre2a0ssJiagnnueadryto2t0h0e0.roTleheofpPrreivnicoiuplsesAtnuadlyytdiicraelctIonrv,esKtriigsatteonr.J. Reason: The role of study director was reassigned in an effort to ensure compliance with Good Laboratory Practice Standards that outline study personnel requirements (refer to 21 CFRPart 58). 2. ProTOCOL READS: The sponsor for the present study was identified as Marvin T. Case, D.V.M., Ph.D. AMEND TO READ: The role of sponsor for the present study was reassigned to John L. Butenhoff, Ph.D., as of 20 January 2000. Reason: To ensure that the study director does not also carry the duties of study sponsor, the sponsor role was reassigned. In this manner, personnel responsibilities and workload are more evenly balanced. Ei Ps = 3M Environmental Laboratory 00971 APmreontdocmoelnLtRNNu-Um2b9e93r4 Amendment Approval Plan 1. Butardirf John L. Butenhoff, Ph.D., Sponsor Representative February 10, zoo Date bite for Kristen J. Hansen, Ph.D., Outgoing Study Director 11 = Foto ~ 2000. Date Marvin T. Case, D.V.M., Ph.D., Incoming Study Director Date %g am Environmental Laboratory 030972 Study Title Oral (Gavage) Pharmacokinetic Recovery Study of PFOS in Rats PROTOCOL AMENDMENT NO. 4 Amendment Date: 20 April 2000 Performing Laboratories Laboratory Project Identification ET&SS LRN-U2994 FACT TOX-111 Argus Study: 418-015 3M Medical Department Study: T-6295.14 3M Environmental Laboratory C0097, 0973 APmreontodcmoelnLtRNNu-mUb2e9r944 This amendment modifies the following portion(s) of the protocol: 1. PROTOCOL READS: The amended section 2.0 text states that this study is designed to determine PFOS in specimensofrat liver, serum, and urine. AMEND TO This study READ: is designed to determine PFOS in specimensof rat liver, serum, feces, and urine. REASON: The analysis of fecal tissue for the target chemical and/or its analytes was added to the scope owfertehensottuvdaylifdoaltleodwianngdtahpepirsosvueadncperoifotrhtoepprroottooccooll.apFpercoevsale.xtraction and analytical methods 2. PROTOCOL READS: The amended section 6.0 lists rat or rabbit liver, serum, and urine. A`AMddE:NrDatToOr RraEbAbDit:feces with a physical description of rat or rabbit feces. REASON: Analysis of fecal tissue for the target chemical and/or its analytes was added to the scope of the study following the issuance of the original protocol. 3. PROTOCOL READS: Section 13.1 lists all ofthe laboratories that will be conducting analyses for this study. AMEND TO READ: `Add: Centre Analytical Laboratories, Inc., 3048 Research Drive, State College, PA 16801 REASON: Feces analyses were added to the scopeofthis study. The sub-contract laboratory performing analyses was not in the original protocol. 4. o 5]? Bl PSeRcOtiToOnCsO1L0.R4EaAnDdS1:1.4 state that if the analyses are sub-coniracted to other laboratories an `amendment wil be written to include these methods. AMEND TO READ: The feces extraction and analytical methodused by Centre Analytical Laboratories will be; 00M-023-003 (Revision 2), "DeterminationofFluorochemical Residues in Monkey/Rat Feces by LC/MS/MS." REASON: The sub-conuact laboratory performing feces analyses was added to the scopeofthis study; this method was not validated and approved prior to protocol approval. 3M Environmental Laboratory. 000974 APmreontdocmoelnLtANNu-mUb2e9r944 This amendment modifies the following portion(s) of the protocol: 1. PROTOCOL READS: The amended section 2.0 text sates that this study is designed to determine PFOS in specimens of rat liver, serum, and urine. AMEND TO READ: TRheiasssotnud:y is designed to determine PFOS in specimens of rat liver, serum, feces, and urine. The analysis of fecal tissue for the target chemical and/or its analytes was added to the scope of the study following the issuance of the protocol. Feces extraction and analytical methods were not validated and approved prior to protocol approval. 2. PROTOCOL READS: `The amended section 6.0 lists rat or rabbit liver, serum, and urine. AMEND TO READ: `Add: rat or rabbit feces with a physical description of rat or rabbit feces. REASON: Analysis of fecal tissue for the target chemical and/or its analytes was added to the scope of the study following the issuance of the original protocol. 3. 4. 5] SSE. Protocol READS: Section 13.1 lists all of the laboratories that will be conducting analyses for this study. AMEND TO READ: `Add: Centre Analytical Laboratories, Inc., 3048 Research Drive, State College, PA 16801 Reason: Feces analyses were added to the scopeof this study. The sub-contract laboratory performing analyses was not in the original protocol. ProTocoL Reads: Sections 10.4 and 11.4 state that if the analyses are sub-contracted to other laboratories an aAmMeEnNdDmeTnOtRwEilAlD:be written to include these methods. The feces extraction and analytical method used by Centre Analytical Laboratories will be; (00M-023-003 (Revision 2), "Determination of Fluorochemical Residues in Monkey/Rat Feces by LC/MS/MS." REASON: The sub-contract laboratory performing feces analyses was added to the scope of this study; this method was not validated and approved prior to protocol approval. =lag g 3M Environmental Laboratory 0975 AmPernotdomcoelntLANNu-mUb2e9r944 Amendment Approval Pom 2. it) John L. Butenhoff, Ph.D., Sponsor Representative Apr! 1% zo oo Date Mgnt Marvin T. Case, D.V.M., Ph.D., Study Director 1 Mp reso Date E32 5g i 3M Environmental Laboratory 0096