Document K6NRgmV8RvEozZe9rmv3KpKQ0
AR126-033| ,
3M MEDICAL DEPARTMENT, CORPORATE TOXICOLOGY
Protocol for Study No. T-6316.17, T-6295.21, T-7132.3; ST-41
Derivatives.
Study Objective: TFhliusosritnuedAyniasldyetsiciaglnCehdtemoigsetnreyraTteeasmpetcoiumseenfsofrodretvheelo3pMmeEnntviarnodnvmaelnitdaatliLoanbaormaettohroyd of feces metabolite analysis
Research Client:
3M Specialty Chemicals Division 3SaMintCePnatuelr,,MBuNil5d5in1g44236
Sponsor:
3M Specialty Chemicals Division
3M Center, Building 236
Saint Paul, MN 55144
Study Location:
3M Strategic Toxicology Laboratory S3aMintCePnatuelr,,MBuNil5d5in1g44270-3S-06 room SB314
StudyDirector: AndrewM. Seacat, Ph.D.
3ToMxiMceodliocgaylSDpeepcti.ali/sCtorporate Toxicology
3M Center, Building 20-26-02
Saint Paul, MN 55144
Ph.: 651-575-3161 FAX: 651-733-1773
Study Taxicologist.
Deanna Lucbker, MS 3AdMvaMnedciecdaRleDseepatr.ch/ CToorxipcoorlaotgeisTtoxicology 3M Center, Building 220-2E-02
Saint Paul, MN 55144
Ph: 651-737-1374 FAX: 651-733-1773
ProposeIdnS-tLiufdeyStTairmtelDiantee:: Monday November 22, 1999 In-Life End Date: Wednesday November 24, 1999
`pTrhoitsosctouldyawnidlcllbasespiefirefdoarsmaed"iCnltahseBs3SMtuSdtyr"ataesgiecxTpolaxiinceodloingyTLOabXoSrOatPo0r9yu5n0d,eSrtraadteegfiicn:ed
.
Toxicology Lab GLP Program Procedure.
005962
T6316.17; T6295.21; T-71323; ST-41
TestMaterial: fDuernniHsahkedesh,igPhr-opduuricttyRNe-spEotnFsiObSiEl,ityPFLiOaSisaonnd3PMFCOhSeAmitcoaltsheDiSvtirsaitoeng,ichTasoxpirceovlioougsylLyab.
Identification: Name: N-EtFOSE: Narrow Range N-Ethyl PpeFrOfSl:uoPreorofcltuaonreosoucltfaonneamSiudlofoentihcanAocli,d,FMP-o3t9as2s3i.um Salt; CAS # P27F9O5S-A3:9-P3erfluorooctanesulfonamide
Molecular Formula;
*
NPF-OESt:FOCSiEF:iC08SFO1;7KS"02N(CH2CH3)CH2CH20H
PFOSA: CiFisSONH,
Lot Number: * `oNn-eEstaFmOpSlEe.: Lots 30035, 30037, 30039mixed and analyzed as PFOS: Lot #217
+ PFOSA: L-10009
Parity:
aNnEdtDFSOCSEt:ech9n8iq%ueass(1d),etermbiynGeCd, GC/MS, "F-NMR, "H-NMR PPFFOOSS:A:>99% as determined by 'F-NMR (2). AnalysisbyGCMSdeterminedthatthestaringmaterialwasover * Qu9a9li%taptuirvee(a3)n.dquaniitativecomposition resultsthatwerederived
tfhraotmtthheecsoimnpgolseittriiaoln'wHa/s*6F5-.N8M%RCcFr3os(sC-Fin2t)exgr-aStOio2n-aNnHa2ly(siNsorremvaelaled c`hmaoinno),me1t8h.y7l%bCraFn3c(hC)F,21)1x.-2C%F((CCFF33))2-C(FC~F(2C)Fy2-)Sx0-2S-0N2H-2N(HI2nternal b(rIasnopcrho)paylndbr0a.n2ch8)%, (3C.F5:%)C:xCFC2Fx2+)1--SCOF7(-CNFH3)(-tS-B0u2t-ylNHb2ra(nAclhp)h4a). * p HPLOCpf/MPSFmOcSh,ar1a,ct1e0r0ipzaptmioonoffC;tFh1esPSFO;ONSHA,,sa5m1p0lpeprmevoeafled 9,600 C`CuoFF1ssSHOS:NOHNs,H,6,610,020p0ppmpofmoCfoCFiFg1H5SHO:;SNOH;,NH2;4,a0n0d0lpopwmerof i`mpcuriotiens,cthee opnufrsitetvyerorfatalhottehPeiFr OaomSinAdesssa.mBpalseewdoounltdhbeeaspupmrooxfitmhaetely 96% (5).
005963 2
.
T3167; T2952 T1323; ST
Stability: Documentation will be kept on file. TSetsotrmaagteerCioanldwiitlilobness:toredtightlysealedat room temperature.
Characteristics: tIhnefotremstatmiaotneroinalswyinltlhebseiskempetthoondsfi,le.`compositionorother characteristics that define
Animals:
Species:
Strain:
Rat
Sprague Dawley
Source:
Harlan
A`Wgeeigahttiantitiinaittiioantioofnotrfetartemaetnmte:nt:
Number and sex: 12 males
`GROUP 1: control, n=3
`GROUP 2: N-Et FOSE, n=3
GROUP 3: PFOS, n=3
`GROUP 4: PFOSA, n=3
Identification: unique tail mark
a9p-p1r1owxiemeaktsely 200-250g
`Husbandry:
Housing: All ratswillbeindividuallyhousedinwirebottom metabolismcagesto allow for collection of urine and feces.
Diet/Water: Harlan Teklad LM-485 Mouse/Rat Sterilizable Diet, supplied by Harlan `Tekdad, Madison, WI, and tapwaterwill be provided to allratsadlibitum throughout the study.
Environment: Environmentalcontrolsforthe animal roomwillbeset tomaintain a temperatoufr7e2 + 3F, humiofd3i 0-t 70y %, aminimumof 10exchanges ofroomairperhourand a12hourlight/darkcycle.
Dose and Dosing Procedures:
Methodofadministration/Dose preparation:
Avlollruamtesowifll5bmelddoosseidngvsiuasopreanlsgiaovnag/kegobnoddayywzeeirgohotf.tRhaetsstiundygusrinog2uawipl
receive asingle400mg/kgdoseof N-EtFOSE,ratsingrou3pwillreceive
a1s0i0ngmlge1/k0g0dmogs/ekogfdPoFsOeSoAf.PFUOniSafonrdmrsautsspienngsiroonuspof4
willreceive
N-Et FOSE
asingle
(8%; 80
mg/mL)andPFOS (2%; 20mg/mL) willbepreparedin 2% Tween 80
using a 15-mltissue grinder. Re-suspeonfsPiFoOnS and N-EtFOSE
solidswilbl eperformedwith Sstrokesofthetissuegrinderpestelbefore
`eachsample is drawn-up inthe syringe for dosing.
005964
3
ee
T3617 T629521; T7032; ST41
`
foPrFmOiSnAga(n2e%m;u2l0sm ion ig n 2%w/ ilTlwbem eepnr8eL 0ptaroe) dabfyinadlcoincsenstroaitlnioavnceiotofnneg1%, then
Abacyseiptnognluee,$52mm%tiphT/ekwieegmebinnosd8i0ygo.wneRtiehg-rhsotuusdgpohesnteshoiesofynroviefhnigPcelFiemOwmiSelAldbisaeotlaieddlmsyiwnbiielslftoberereepddevorsifinogr.med
graecveaigveet2o%raTtwseienngro8u0apn1don1 wdialylzreecreoiovfetahmeisxttuudrye.ofTw1o%oafctehteornaet/s2w%ialoral
Tween 80.
ObservofaAtniimaolsn:
ClinicaElaOcbhsearnviamtailownisl:lbeobserveddailyformortality andmorbidityand notable
findingswillberecorded. observed.
Additional
findingswillberecorded
as
theyare
Body Weights:
Eiacmh amnimealdpwriiliolrbateowetuetiehgahneladsiiymam.ediatelypriortotreatmentand
Freque`nOcnyecaonndtrNoulamnbdeornoefPAnFiOmSaAlrsa:twillbesacrificedonday 1postdose. All
remaininganimalswil besacrificedonday2-postdose.
SpecimenCollection & Analysis: MethodUorifnSepaencdifmeecensCwoillllebcteicoonl:lectedfromeachmetabolismcage ondaysone oafntdhtewuoripnoesctodlloescet.ioTnhaepipnairtaitaulvsowliullmbeeofwausrihneedwwiiltlbhe5r-e1c0ormdledde,itohneizseiddes w`iwlaltbeerarndethecfifnooalrvreoalcudhmaeneoifmadulr.inewilberecorded.Dailyfeces weight Anneicmroaplssyw,ibllloboedeu(txh6amnii)zewdibllybeCcOo;lalnecdtgerdovisastnheceraobpdsoympinearlfoaromretda.aDnudring wtirlalbnsefaelrlrotewoeddbtlooocdloctoflolrecatpioenrtiuobdeosfwi1t5htoout30anmtiincuotageuslaatntr.oBolmood samples tmemipneurtaetsu.rTeh,aensdetrhuecmlvoiltlwbileltrbeansspfuernrdedotwonliabnealceedn1t.r5ifmulgemaitcr1of1u0g0extgufboers Eaancdhcesnetrraisfuagmepdlaegwaiilnlatthe2n0b0e0dixvgitdoedrienmtoov2eaalniqyuroetms,atirnainnsgfreerrdebdlotoodacells saelpiaquroattewillalbbeeleudspeodlfyporrompeytlaebnoelmiitceraonfaliyisgiestaunbdeatnhdeoftrhoezrefnoirnbdiroycihceem.icOanle analysis. Eachliverwillbe excised andweighed. Theliverwillbeflash rferomzoevneidnalinqduisdtonrietdroagten~.7A0sCmfaolrlsmeecttaiboonli(taepapnraolxyisimsa.teTlyhe3 grreammsa)iwnildlwebilrel sbaecrsitfoirceeddaotn-d7a0y2C-fpoorsbtidoocsheemwiiclableaenaxlcyissise.d,Kweiighdedfrnaonmdeafnlyaismhasflrsozenin liquidnitrogenforfuturebiochemical analysis.
005965 *
T316.1% T2952); T1323; ST41
,
Specimen Handling:
Atlelmuproiranreialnydsfteocreedsaant d-t7h0esCienrtuhmeanStdraltievgeirfc oTromxeitcaobloolgiyteLaanbaolryastiosryw.illFboer
analysis,thesesampleswil bepackedindry iceandshipped to:
KrisHansen, Ph.D.
3MEnvironmental Technology andSafetyServices 935 Bush Avenue
St. Paul, MN 55133-3331
`Telephone No.: 651-778-6081, Facsimile No.651-778-6176.
AthlelSktirdanteeygsipceTcoixmiecnolsoagnydltahbefroermbaiioncdheermiocfaslearnaulmyasinsd.lTihveersweislplbeceikmeepntsin will be storedat -70C.
Tfhoellmouwsm:ber, type,anddateofspecimenstobe generatedforanalysisareas
TABLE 1 Specimens for EnvironmentLalb
`Specimen.
Emvironmental Urine LebSpecimens [Fews
1[T 1122-- 30 Tio15[] 2]
[sem [ve
T1T o2 o ToT, Ti]
StrategicTacLab[Sem Specimens [ve
7[T 2 o TyoT] 1, |
[Kio
7
Tio
Tio]
DataAnalysis: Allesuitswillbeprovidedforinclusionin the finalreport.
ResDcpoeolnalsneicbntiailniLgtiiunee-sbl:kifeersapnedciAmnednrse,pweSrefaocramtinwgiltlhbeenreecsrpoopsniseisblaefnodrcdololseicntgitnghaeanndimsaelndsi,ng AtinsdsureeswSpeaecactwifiolmrladenraaflntysaisfsi.nalreportandensurethereportreceivesappropriate 3M reviewbefore afinalreportis issued.
005966
s
Signatures:
Dr. Andrew Seacat Senior Research Toxicologist Study Director
Deanna J. Luebker, Advanced Toxicologist Study Toxicologist
TAG T9521 TAY, STL
Date
/
9
Date
005967
T4316.17 T6295.21; T7123; ST41
,
References:
1. PayfTerw,oRY.eCahrarFaecetedriinzgatSitoudnyo.fFSMM-3D92A3na,lyMtiixctaulrReeoqfuLeostts#5320408395., 3A0na0l3y7ti&cal30R0e3p9orftor# 816, 6/23/97. 3M`SMDLab Building236-2B-11.
2. KestSapeerc,tTr.osFcuoopryoRcehqeumeisctal#I5s3o0m3e0.r D3isMtrSipbeuctiiaolntbyyAd"hFes-iNvMesR&SpCehctermoisccaolpsy.Analytical Labo/SrMMaD-2t36o-2Br-1y1, December 1, 1997.
3. Payf5e9r,42R6.GRCep/oMrSt 9a/n2a4l/ys9i9s. o3fMPFSOAS&AC(LLa-1b0B0u0i9l)d.inSgA23&6C-2ABn-a1l1y.tical Request No.
4. SpKeescttnreors,cTo.pCyhReemqiuceasltCh#a5r9ac4t2e6r,iz3aMtioSnpoecfiPalFtOySAAd,hesLi-v1es00&0Ch9bey,mi1cHaalnsdAn1a9lyFt-iNcMalR. Laborator/y SMMD-236-2B-11,September 25, 1999.
S. DeRoos F. CharacterizationofPFOSA Samples, T-7132-1 (L-10009) and TN-ACC1oh5r8rp4o.omraRatetoqegurAenasaptlhy#ytiAGc-ra1ol5uT1pe2.c5h4n.olRoegpyorCten1t0e/r7,/B99u,ialdnidnLge2t0te1r.1a2d9d,eCndAuTmCto--report 10/14/99.
005968
7