Document jyNYz8drj0rabJ1XX9dKZBGpR
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3M MEDICAL DEPARTMENT, CORPORATE TOXICOLOGY
Protocol for Study No. T-6316.17, T-6295.21, T-7132.3; ST-41
Derivatives.
"STthiusdsytuOdbjyeicstdievsei:gnedtogeneratespecimensforthe3M EnvironmentalLaboratory FluorineAnalytical Chemistry Teamtousefor developmentandvalidation amethodof feces metabolite analysis.
Research Client:
3M Specialty Chemicals Division 3M Center, Building 236
Saint Paul, MN 55144
Sponsor:
3M Specialty Chemicals Division 3M Center, Building 236
Saint Paul, MN 55144
Study Location:
3M Strategic Toxicology Laboratory 3SaMintCePnatuelr,,MBuNil5d5in1g44270-3S-06 room SB314
StudyDirector: ~~ Andrew M. Seacat, Ph.D.
3
Toxicology Specialist
3M Medical Dept. /Corporate Toxicology
3M Center, Building 220-202
Saint Paul, MN 55144
Ph.: 651-575-3161 FAX: 651-733-1773
Study Taxicologist:
DAdevaannncaeLdueRbekseera,rcMhSToxicologist 3M Medical Dept. / Corporate Toxicology 3M Center, Building 220-2E-02 Saint Paul, MN 55144
Ph: 651-737-1374 FAX: 651-733-1773
ProposeIdn-SLtiufdeyStTairmtelDiantee:: Monday November 22, 1999 In-Life End Date: Wednesday November 24, 1999
Regulatory Compliance:
Tphisrstoudaytnwdiclollabscesipfoeirefdlaorsmea"dCilnatshseB3MStSutdrya"taesgiecxpTloaxiinceodliongyTLOabXoSraOtPor0y9u5n0d,erStardateefgiinced Toxicology Lab GLP Program Procedure.
000146
T316.17; T2952; T-7132.3; ST-41
Test Material: Dan Hakes, Product Responsibility Liaison 3M Chemicals Division, has previously furnisheIddehnitgihf-ipcuartiitoynN:-EtFOSE, PFOS and PFOSA to the Strategic Toxicology Lab.
Name:
N-EtFOSE: Narrow Range N-Ethyl pPeFrOfSl:uoPreorofcltuaonreosoucltfaonneamSiudlofoentihcanAocli,d,FMP-o3t9as2s3i.um Salt; CAS # P2F79O5S-A3:93Perfluorooctanesulfonamide
`Molecular Formula:
N-PEFtOFS:OSCEi:F/C08SF01;7KS"O2N(CH2CH3)CH2CH20H
* PFOSA: CiF17SO;NH,
Lot Number:
* N-EtFOSE: Lots 30035, 30037, 30039 mixed andanalyzedas
one sample.
* PFOS: Lot #217 * PFOSA: L-10009
Parity:
*
*
NEtFOSE: 98 % as determined byGC, GC/MS, "F-NMR, H-NMR
and DSC techniques (1).
PFOS: >99%as determined by "*F-NMR(2).
PFAOnSaAly:sisby GCM determinedthatthestaringmaterial wasover
99% pure (3).
Qualitativeandquantitativecompositionalresultsthatwere derived
tfhraotmtthheecsoimnpgolseittriiaoln'wHa/s'*6F5-.N8M%RCcFr3os(sC-Fin2t)exgr-aSt0io2n-aNnHa2lys(iNsorremvaelaled
h`amionn)o,me1t8h.y7l%bCraFn3c(hC)F,21)1x.-2C%F((CCFF33))2-C(FC-E(2C)Fy2-)Sx0-2S-0N2H-2N(HI2nternal
b(rIasonpcrho)paylndbr0a.n2ch8)%, (3C.F5s%)C:CxCFF2yx)+y1--SCOF7(-CNFH3()t--SB0u2t-ylNHb2ran(cAhl)p(h4a).
HPLC/MS characterizationofthePFOSA sample revealed 9,600
ppmofPFOS,
CoF15S0:NHs,
1,100
6,600
ppppmmooffCC;yFF11scSHO,SNOH:;N,H,51204p,p00m0
opfp
m
of
cConuceFnHtrSatOioNnsHo,fs1e,v2e0r0alpoptmhoerfaCm,idFe1s5.HBzaSsOeNdoHn; tahnedsluomweorfthe
impurities,thepurity ofthe PFOSAsamplewouldbeapproximately
96 % (5).
000147
2
T3617, T-6295.21; T-71323; ST41
SSttaobrialgitey:CoDnodciutmieonntsa:tion will be kept on file. `CTheasrtamcatteerriisatliwcisl:l be stored tightly sealed at room temperature. tIhnefotremsatmtaitoenroianslywnitlhebseiksempettohnodfsil,e.compositionorothercharacteristics that define
AnimalsS;pecies: Rat Strain: Sprague Dawley Source: Harlan AWegiegahttiantitiinaittiioantioofnotrfetartemaetnmte:nt: NumberGRaOndUsPex1:: cont1r2olm,alne=s3
`GROUP 2: N-Et FOSE, n=3
GGRROOUUPP 34:: PPFFOOSS,A,r=n3=3 Identification: unique tail mark
a9p-p1r1owxiemeaktsely
200-2503
Husbandry: `Housing: aAllllorwatfsowriclollbleecitniodnoifvuiridnuehaaonludsleyfdeicensw.irebottom metaboclagiesstmo Diet/Water: `HTaerkllaadn,TMeakdliasdoLnM,-W4I8,5anMdotuaspew/aRtaetrSwtielrlibizeapbrloevDiidete,dtsuopaplllireadtsbaydHlairbliantum throughout the study.
EnviroEnnmveinrto:nmentalcontrolsfortheanimalroom willbeset tomaintain a
temperatureof 72 + 3F, `of roomairperhourand
ah1u2mihdoiutyrolifg3ht0/-d7a0r%kc,ycamlei.nimumof
10
exchanges
DoseandDosing Procedures:
MethodAollfraadtmswiinlilsbtreadtoisoend/vDioasoeraprlegpaavraagteioonn:dayzeroofthestudyusing a vroelceuimveeoafsi5ngmlled4o0s0inmggs/uksgpdeonssieoonf/ kN-gEbtoFdOySweEi,grhatts. iRnagtrsoiunpg3rwilol2ruewcipelilve. asingle 100 mg/kgdoseof PFOSandratsingroup 4willreceive asingle mg1/00mmLg)/akngdd PFOo oSf(Ps 2F%O;SeA20.mUgn/imfLo)rwmisllubseppreepnarsoeifdioNn-n2Est%FTwOeSeEn(88%0; 80 using a 15-m tissue grinder. Re-suspensionof PFOS and N-EtFOSE seoalcihdssawmipllbeeipsedrrawfn-ourpwimintethhdSessytrrionkgeesfoofrthdoestiinsgs.uegrinderpestelbefore
000148
3
T3617T6295.21; T7123;ST41
!
fPorFmOiSngAa(n2e%m;ul2s0imogn/imn2L)%wiTllwbeeenpr8e0patroedafbiynadlicsosnocelnvtirinangtiaocnoetfon1e,%then
bay pcumepi2tn%goTthwneeeeemnul8,s0i.onRthreough-thessyroiufngPeFsiOmSmpAedsioealtiedlsnywibleslfboreeipedorsofionrgn.med
gAsinaglteov5ramta ls i/kngg grbooue dpy1weoingdhatydzoesreoooffvethhiecslteuwdiyl.lTbewaodomifntihsetreartesdwviilaloral
receive 2% Tween 80and 1willreceive amixtureof 1%acetone/2%
`Tween80.
ObservofaAtniimaolsn: Clinicaf`liEnaOdcbihsnaegnrsviwamitalillowbnieslr:lebceorodbesde.rvAedddidtaiiolnyaflofrimnodritnaglsiwtiylalnbdermoercboirddietdyaasntdhneoytaarbele
observed.
BodyWEeaicghhtasn:imalwillbe weighedimmediatelypriortotreatment and immedpriioratoetutheanlasiya.
Freque`nOcnyecaonndtrNoulamnbdeornoefAPnFiOmSalAsr:atwillbesacrificedonday 1post dose. All remaining animals will be sacrificed on day 2-post dose.
SpecimenCollection &Analysis: Methodof Specimen Collection: aUnridntewaondpofsetcdeoswsie.llTbheecionlilteicatlevdoflruommeeoafcuhrmienteawbiolllbiesmreccaogredoedn,dtahyessoidnees `owfattehreuarnidntehceolfliencatlvioonlaupmpearoaftuursiwneiwliblelbwearsehceodrwdeidt.h 5D-a1il0ymfiedceeisowneiizgehdt wAinilmbaelrs wielbceefouotrhreanaicdzheadenbimydaCl,O;andgrossnecropsy performed. During ntercarnosfpesryr,edbltooobdl(oxod6cmoil)lewcitlilobnteucbolelsewcittehdovuitatanhteiacboadgoumliannta.lBaolrotoadasnadmples `tweilmlpbeeraatlulroew,eadndttochleoctlfootrwiaplelbrieodspuonfd1o5 wtnoi3n0maicnenuttreisfautgeraotom1100x gfor anSmdincuetnetsr.ifTuhgeedsaegrauimnwaitl2l0b0e0trxangsfteorrreemdotvoelaabneylreedm1a.i5nmiingmriecdrobfluogoedcteulbless. Eseapcarhasteeralsabaemlpeldepwoillylptrhoepnybleendeivmideidintcot2uarbleiqauo nodtfsr,ftorzaenusifnedrgrreyditecoe.a One a`lainaqluyositsw.iElabcehuisveedrfwoirllmbeteaebxocliisteedanaanldywsiesiagnhdetdh.eTohtehleirvfeor rwiblilobcehfelmiacsahl frreomzoevneidnalniqdusitdonrietdraogten~.7A0sCmfaolrlsmeecttaiboonli(taepapnraolxyismias.teTlhy e3 rgreammas)iwnildwlebielr:l sbacersitfoirceeddaotnd-7a0y2C-fpoorsbtidooscewhilelmbaeineacxlcyaisislse.d,Kweiighdefdrnaonmdeafnliyamsahsflrsozenin liquid nitrogen forfuture biochemicalanalysis.
000149
4
T3617, T29521; T-1132.3; ST41
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Specimen Handling:
`Allurineandfecesandtheserumandliverformetaboliteanalysis wil be
temporarily stored at -70Cinthe Strategic Toxicology Laboratory. For
analysis,thesesampleswillbepackedindry iceandshipped to:
Kr3iMEsHannsevn,Pih.Dr.Tecohnonlogmyaned SnafettySearvilces 9St3.5PaBuuls,hMANven5u5e1333331
`Telephone No.: 651-778-6081, FacsimileNo.: 651-778-6176.
AtlhlekSitdrnaetyegsipceTcimoenxsanidltachbefrooermblaiionocdheergmoifcyaslearnualmyasnisd.Tlihveersweilslpbeecikmeepntsin willbestoart-7e0dC.
`The mumber,type,anddateofspecimenstobegeneratedforanalysisareas follows:
TN a == re TABLE 1 -SpecimensforEnvironmentLaalb
Environmental [Urine
112
Two
5|
LabSpecimens [Fees ~~ lip
[10
[2 |
sm
To
The
Ti|
five
To
Two
Tn|
StrategicTaxLab[Sew
[2
[0
Tn |
Specimens fiT ve oo To|
[Koogs 1
Two
Tio]
DataAnalysis: Allresultswillbeprovidedforinclusioninthefina report.
Responsibilities: cDoelalencntainLguienb-lkfeersapnedcAimnednrse,pweSrefaocramtinwgitlhbeenreecsrpoopnssiiebslaenfodrcoldloescitnigtngheaanndimsaelnsd,ing
tissue specifomranealnysiss. Andrew reviewbeSfeoarceatafwiinlalldrreapfotratfiisniaslsrueepdo.rtandensurethereportreceivesappropriate 3M
000150
s
Signatures:
TG3UGIT, T29521; T1323; STL
Dr. Andrew Seacat
Senior ResearchToxicologist
Study Director
Date
f
Llesacg outs_ufousra Deanna J. Luebker, Advanced Toxicologist Study Toxicologist
Date
000151
6
T3167; T629521; T-71323; ST41
Ph
References:
1.
PayfTerw,oR.YeCaharrFaecetedriinzgatSitoundyo.f FSMM-3D92An3a,lyMtiixctaulrReeoqfuLesotts#5320408395., 816, 6/23/97. 3MSMDLabBuilding 236-2B-11.
30037 & 30039 for Analytical Report #
2. KestL Sepre,ca tTr.osFb clou/poyrSooMRceMhqDer um-ei2sc3taa 6l#-I25s3t Bo0-m3e01.r1oD,3iDsMetrrcSiepbmeuy cbtiieaorlntby1y,A1Fd9h-97eN.sMivRe&SspCechtermoisccaolpsy.Analytical 3. Payf5e9r,42R6.. GReCp/oMrSta9n/a2l4y/s9i9s. o3fMPFSOAS&AC(LLa-1b0B0u0i9l)d.inSgA23&6C-2ABn-a1l1y.tical Request No.
4. SLKpaeebsctoterrrao,tscoTor./pyCyhSReMemMqiDuc-ea2sl3tC6#-h529aB4r-21a61.c,3tSMeeSrpptieoeczmfibaaPeltFrtOyi2SA5oA,dn,h1e9Ls9-i91v.0e0s0&9C,hbeymi1cHalansdAn1a9lyFt-iNcMalR_
5. CD1o5er8Rp4o.oorRasetqFe.uAeCnshatalry#atciAtc-ea1rl5iT1zea2ct5ih4on,noolRfoegPpyoFrCOteSn1tA0e/rS7,/aB9mu9pi,llaedsni,ndgTLe-2t70t11e3-r21a-2d19d(,eLnC-d1Au0Tm00Ct9o)--raenpdorTtN1-0A/-14/99, Chromatography Group.
000152
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