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Study Title: Acute Inhalation Toxicokinetic StudyofPerfluoroctanesulfony! Fluoride (POSF) T-7098.4
`Test Number (sample): T-7098.4 (Perfluoroctanesulfonyl Fluoride (POSF) Laboratory Project Identification: ~~ ST64
IInn--LLiiffee ICnoimtpialteitonioDnatDea:te: 55//11/42/0200101
Research Client:
3M Specialty Materials Division 3M Center Building 236
Saint Paul, MN 55133-3220
Testing Laboratory: ~ 3M Strategic Toxicology Laboratory
3M Center Building 270-SB-181 Saint Paul, MN 55133-3220
Study Director:
Study Toxicologist:
TAanxdircoelwogMi.stSeSapcecaita,lPihst.D.
3M Medical Department/Toxicology Services
3M Center Building 220-2E-02 Saint Paul, MN 55133-3220
TPoosmtmDioectYovreatltReeTsueranrecrh, FPeh.lDl.ow
3M Medical Department/Toxicology Services 3M Center Building 220-2E-02
`Saint Paul, MN 55133-3220
=
=5E 33S2aa = 35
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7Fi.n7a0l9R8e4poArctuteInhalation Toxicokinetic Study ofPerflucroctanesifony] Fluoride (POSE)
Summary:
controlA(anr-aocnultye)iannhadla3tmioanletorxaitcsokeixnpeotsiecdsctroepeenrfwlausorcoocntdaunecstueldfounsyi]ngfl3uomraildee (raPtOsSfFor) ata `rneocmoivnearlycpoenrcieondtraantdiosnhoofwe1d00n0opcplimnicfaol4rpahtohuorlso.gyA.ll animals gained weightduringthe
on day O1,ndeayan6imaanld(dNa=y1)14peprostti-meexppoosiunrte.frAolml tahneimPaOlSsF-ttolreeraatteedd tahneim4a-lhsouwraisnhsaaclraitfiiocned ethxepolsivuerre, alunndgsg,abilnaedddweeri,gkhitd.nOerygaanndwberiagihntrsevweearleednonromsailgnainfdichainsttofliongdiicnagls.evaluation of
at8.6,9P.e3raflnudor5o.0ocptpanmeosufldfaoynsate1,(6FaOnSd)1w4apsosftoduonsde,inretshpeecsteirvuelmy.frTohmeepaecrhceanntiamgaelo(fN=1) inhaled POSF represented by these serum PFOS concentrations were 0.18%, 0.23%, and 0.10%, respectively.
total POCSoFncilnuhsailoend:fTohuinssdtausdPyFdOeSmoinnstsreartuemsctohlaltetchteerdeowvaesr a14smdaaylsl.pReerscuelnttsagseh(o<w0t.h5a%t) of tahbesroerbweadsfnroomsitgnhiefliucnagn,tacnhdanmgeetianbPoFlOiSzitenodsePrFuOmS,cownhciecnthriastpironesoevterintismeer.umPOfSorFgrceaantebre than 14 days.
1 Study Objective:
inhalati"oTnhoisfspteurfdlyuworaosctdaonneesutlofoensyt!alblfilsuhotroixdiec(oPkOiSneFt)i.cTpahreamgeotalesrosfdtathaiosntuadnyawcuetre:e to test t`hmeetcaobomlpiosmu,ndanvdiatoinuhsaelatthieorneisnulrtassasata 1g0u0i0dapnpcem ffoorra4 1h3ouwresfeokridnihsatlraitbiuotnisotnudayn.d
IL Test Articles: A. Identification:
TM Name 0983 POSF
Structure CiFnSOF
MW (g/mole) Density (g/ml)
502
169
B. Purity and Stability: Responsibilityofresearch client. This POSF sample was lab,
fNrMacRtioannadte'd'aFn-dNaMcRidS/wpaetcetrrowsacsohpeyd.waCshecmoincdaulctcehdarbayct3erMizSapteicoinoalftyCyAFdh1e7sSiOvZeFsb&y 'H-
CprhoedmuicctaalnsdAntaolcyhtaircaaclteLraibzoeraatsomray!nSyMimDputroitdyefceormmpionneetnhtespuarsiptoyossfibtlhee. nTohmeinsaalmple was found 10 be a high purity form ofthe nominal POSF product (1).
C. Handling and Storage: Upon receipt, the test article was stored tightly sealed at room temperature.
2
F7i0pa9l8R.e4porAtcuic Inhalation ToxicokineicStyofPerioroctanesulfosylForide (POSE)
--- D. rDeistpuomseidtitoontohferTeessetarMcathcerliiaeln:taAfntyerrceommapilneitnigounonfutsehdepsotrutdiyo.nofthe test article was
DL Test System:
liter glaMssaleexrpaotssuwreerceheaxmpboesre(d3troattess/tchcaommbpeor/ucnodmpionauinrdf)o.rT4hehofulroswf-otrhroonueghdaaytmionsaph1e3re
f`wlaoswigenngearta3t,e0d Lb/ymmiinxiinntgo ttehset cchoammpboeurnadnfdreoxmhaaussytreidngtehrpouumghpainvteonta.sTthreeasmyorifnfgreesfhloswir
ratewas calculatedbasedonthe Ideal Gas Law equation:
(ot concentration)(MW)/(24.79L)
x
(1/10
pg)x
(airflow
rate)
x
(1/density)
x
(1000
Given:
`Target MW =
cgo/nmcoelnetration
(ppm)
|
24.79L:Thevolumeofone moleofan ideal
`conversion factor: (1 gram)/(1 x 10%1g)
gas
at
25
C
and
I
atmosphere
(760
mm
Hg)
aieflow rate: (min) -.-
density: (mLig)
conversion factor: 1000 limL
airflow`rTahtee twaerrgeetccaolnccuelnattreadtuisoinnsogftheeacIdheatlesGtacsomLpaowunadn,dtahreespyrroivnigdeedflionwtrhaetfeoalnldowtihneg
table:
Dose Group
c
Syringe Flow Rate Airflow Rate
Treated: POSE (1p0p0m0) (3W0min)
(2W0Um-i3n)0
Toxicokinetic group
Control:Aironly
20-30
FourierSTtraanndsafrodrtmarIgneftrcaornecdeSnptercattiroonmseftorry (eFaTcIhRc)o.mCphoaumnbderwaeirrewparsepmaorneidtaonrdeadnbaylyFzTeIdRby nforeconccentetroamstaiionsntsaoaifnatreslteycveolmopfoautnldeaasntd1o0x0y0gpepnm(.2C).onAtirrofllaowniwmaaslsinwcerreaeesexdpowsheedntoroom raiartsuunsdeedr ienqtuhiivsaslteuntdychwaemrbeearlscoonudsietdifoonrstahsetchoentPrOoSlFgrdoouspeignrtohuepliamniitmtalse.oTfhsePOctoSnFtrol (T-7098.3) conducted at the same time.
LARC pArnoitmocaolls#we2r0e0h0a-n0d0l6e8d.iTnheacdcaoyordfadncoesiwnigthwaansadneismiaglnuatseadgdeparyozteorcooolftahpeprsotvueddy.by Body weights were determined immediately prior to dosing and immediately prior to
3
2Fi.n7a0l9R8e.porAtcute Inhalation ToxicokineticStudyofPrflucrocancsfonyl Fluoride (POSF)
euthanasia. At the terminationofthe study, all animals were humanely euthanized by
CO; asphyxiation and necropsies were performed.
Blood serum was collected from one animal/time point of the toxicokinetic group
sacrificed at
PFOS levels
day1, day 6, and
by high-pressure
at day
liquid
14 post exposure for PFOS analysis. Analysis
chromatography/tandem electrospray mass
of
spectroscopy (HPLC-MS/MS) was performed according to published methods (3).
ext`rSaeanrudmcqufatrnotmeiftihdeedrabtysLacCr/ifMiSce/dMdSabyasoneedpoonstadPoFseOS(Asnimtala#cRnu0r1vd4e6ea8xt)rrwacatsdediniftriaolmly
urine collected from the limit toxicity study in rats (T-7098.3). This was done to get an. estiomfsaetruem PFOS leovndeal yonse post-dose assuming an equal extraction of
uuqrusiaenndetiPifnFiaOendSyagcsaatildncsuctluaratviseotnaasnn,ddbsauretdricutumirsvPieFnOecxSltu.rdSaecedtrehudermfefrfroomormsceotrmhupimls,eatanenindmeastlshew(raTesaflboarlteeetr4h)ei.xstdraatcatewdasanndot
Lungs, liver, and bladder were collected at sacrifice. A portionof each tissue was rimemmeadiinaitneglsyecftiixoendsiwneare10pl%acfeodrmdailrienctsloyliunttioonprfooprysluebnseeqtuuebenst fhiilslteodlwogiitchallieqvuailduantiitorno.geTnhe for possible future evaluationofPOSF metabolites levels.
IV. Results and Discussion:
TestAtmosphere
The POSF atmosphere generated in the exposure chamber, measured continuously
for four hours by FTIR, averaged 932 + 93 ppm for the toxicokinetic group (4). The
ctahhveeartmaobgxeeircmocekoiannsceuetnritecrdagtrciooounnpc..enTthraetaiiornfilnowthweacshianmcbreerasweadsfr9o3m%2of1t0h3elittaerrsg/etmicnouncteensttroataidojnufsotr
ControlGroup:
during tThhee4thhrreaer-coonntlryolexgproosuuprem.aTleheraatvsehraadgenoboaddyvewresiegchltinwiacasl 3o7b8s:erv1at2igoanst ntoheted
initiation of the study. The control group gained an average of 22 g (5.5%)of body `weight during the 14 day study period. Liver weights averaged 14.1% 1.0 g and the average liver to body weight ratio was 0.035 (Table1).
Necropsy findings and the histopathology report by Dr. Elden Lamprecht, 3M Surgicaland Histopathology Services, is found in Appendix 1. All ra lungs (both control
and treated groups) had mild to moderate congestion of alveoli with occasional `extravasation of blood around arterioles and bronchioles. This is possibly an agonal change associated with CO; euthanasia. It was noted that someofthe lungs were not
.
Fi7d0a9l8R.e4poArtce Inhaluion Toricokinetc StudyofPerluorocancsufonyl Fluoride (POS)
`cwheallngienssuifnfllauendg.sOatnhderutrhinaanrytbhleasdedaerrtiifnactasl,thhirseteoloofgtihcael caonnatlryosliss.revealed no significant
PTOSoxicokineGtroiupc:
the in-li`fTehephtahsreeeoPfOthSeFragtrs.ouAlplmaanliemraaltss gsahionweeddweniogahdtvdeurrsiencglitnhiecasltuodbys.erAvtatnieocnrsopdusryi,nngo alibvneorrwmeailghgtrso.sHsiosbtsoelrovgiactailonasnawleyrseismiandeo.neoLfivtehreweaingihmtaslswerreeveeaqlueidvathlaetntonteo tmhaecrcoonstcrooplic cfhorcounsiocfaitneldeucrtaatsiiosn a(cnodllwaapssendotalcvoenolsii)dewraesdptroebseenctoimnpotuhnedl-urneglalotbeed..TThheercehawnegreeanpopeared significant changes in the bladder.
seruAmtfnoreceraocphsyifnodirvciaducahlaanniimmaall,t(hTearbelew3a)s. aPesrmfallulorpoeorccteannteasguelfoofnaPtOeS(FPFmOeSa)suwraesd finoutnhde
idnosteh,erseespreucmtifverloym. eTahceh apenricmeanlt(agNe=1o)f aitnh8a.l6e,d9.P3OaSnFdr5e.p0rpespemntoefddbayysth1e,s6e saenrdum14PpFoOstS
csoenrcuemntPrFatOiSoncsownceernetr0a.t1i8o%n,s 0w.e2r3e%a,taonrdne0a.r10t%he,irreaspppeacrteinvtelpye.aTkhecosnecdeanttarastuigognessftotrhtahtethe
ffiorlstlowweienkg wfeoellko.wAilngtheoxupgohsutrheeraenids tnhoesntaPtFisOtiScablepgoawnetroicnltehaer fprreosmentthestsuedryu,mthoevedrattaheare
consistent with a plasma elimination half-life of "`C following of ["*CIFC-95 (mean dose 4.2 mg/kg) to male rats of 7.5 days
single (5).
oral
administration
`analyzeRd afot#r PRFOO1S4.6T8hweacsalscauclraitfiiocenodfosnedrauym1PpFosOtSdwoases abnadsesderoanwuarsinceolPlFeOctSedsatannddard couvrevret,iames,sucmolilnegcteeqduaolnedxatyrasct1,io6n, (aFnidgu1r4ep1o)s.tT-hxepaomsuoruentwoafsP25F.O9S0 +in1s.e10rupmpamve(rTaagbelde 4). eSxetrruacmtferdofmrtohmissearnuimm.alThweasdaltaatedreerxvtirvaecdtefdraonmtdhqeuaPnFtiOfSiedstaagnadianrsdt causrtvaend(asrhdowcunrivnetable 4c)omepxltertaecnteesdsf.rom urine wasnotused in any calculations, but it is included here for
greater `tThhains 1to0x0i0copkpinmetiincasntuidnyhacloantifoinrmleimditeatrolxyicfiitnydsitngusdyooffaPPOOSSFF(46-).hoIunrtrhaetlLiCmisto sdtuurdayt,iornaotsftwheeresteuxdpyo.sTehdetcoo1n0c0e0ntprpatmioPnOoSfFPfoFrOfSoutrhahtouwrass.. Afloluanndiimnatlhsessuerrvuivmedonthdeay 01.30p1o%stodfothseeinwhaasle4d.5d7os+e.0o.f70POpSpFm. T(hN=e3a)vewrhaigceharmeopurenstenotfePdFaOppSroixnitmhaetdealyy-0o.n1e0% 0ov.e0r3n%igohnt tuhreinienwhaalsed3d.o0s8e+of1.6P0OpSpFm(6()N.=T3h)usw,hithcehdraetparefsreonmtetdheapPpOrSoxFimliamtietltyes0t.a0n5d&the dsuaptpaofrrtotmhethseatmoexiccoonkcilnuesliiocntse.st presented herein are in agreement with each other and
s
5.70984 AcuteInhalation ToxicokineicStdyof esluoroctaneulfony| lside (POSF)
FirhkReport
V. Conclusion: inhaled"fTohiusndsatusdPyFdOemSoinstsreartuemsctohlaltetchteeredowvaesra1s4mdaalyls.peRrecseunlttasgseh(o<w0t.h5a%t)othfetroetawlaPs0OS0E significant change in POSF in serum concentration over time.
6
FiT-a7t09R8e.p4oAncute Inhalation Tosicokintc StudyofPerfuoroctanesulfony! Fluoride (POSF)
VI. References: 1. SKepsetcnterro,scTo.pCy.he3mMicSaplecCihaalrtayctMeartiezraitailosn &ofMPaOnuSfFac(tFuMr-i3n2g7D0i)vibsyio"nHA-nNalMyRti&calF-NMR
Laboratory. Request No. 6370. May 15, 2001 2. Modified EPA Method 320. Pace Analytical. 3. HSpaencsiefnic,,KQ.uJa.,ntCilteamtievne,CLh.aAr.a,ctEelrliezfastoin,onMoEf.OragnadniJcohFnlsuoonr,ocHh.em.ic(a2l0s01i)nCBioomlpogoiucnald
Matrices. Environ Sci and Tech., 35, 766-770. 4. GLaubtozrkaotwo,ryT.RePqOueSsFtANnoi.maEOl1-E0x6p4o8s.ur3eMTeEsTtAR&eSpoSrtF.iePladcAenaAlnyatliyctailcaSlerSveircveicseasn,dInc. 3M
Technologies. 5. Joroahlnsdoosne,.J.PDr.ojaenctdONboe.r8,9R00E31.01290709,.RAibkseorrLpatbioornatoofriFeCs,-9In5c.-,1St4i.CnParualt,s afMtNer.a single: 6. SPeerdfaltu,ooAc.taannedsuTlufmoenyrl,FTl.uo(r2i0d0e1)(PAcOuStFe) ITn-h7a0l9a8t.i3o.n Limit Toxicity Study of
7
Tr pm 7098. AcuteIbalaton Tosicokineic StdofPerflucrocaneslfony Farid (POSP)
VI._Signature Page
`Authors: J
< p EAs Tommie Yvette Tumer, Ph.D,
Date 7 /
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Appendix1
HistopathologyResults Necropsy 5/3/01
All rats lungshavegeneralized mildto`moderatecongestionofalveoli with
`poocscsaisbiloynaalneaxgtroanvaalscahtiaonngeofasbsloocoidataerdowuintdhaCrtOe2rioeluetshaannadsibar.onSchoimoelelsu.nTghsiwseirse not
well insufflated.
Animal #
Control RO1462:
Nosignificant changes in lung and bladder.
`NTooxsiicgonkiifniectainct
RO1468:
changes in
lung
and
bladder.
"Toxicokinetic RO1471:
One macroscopic focusofatelectasis (collapsed alveoli) is present in one. lung
lobe. The change was chronic in duration. No significant change is present is bladder.
`Toxicokinetic RO1472: No significant changes inlungand bladder.
T-7098.4 Acute Inhalation Toxicokinetic StudyofPerlucoctnesulfony) Fluoride (POSF) 18 Final Report
Appendix 2 SerumPFOS
To: AndrewSeacaUS-Corporate/SM/US@3M-Corporate "3Tommie TuJmoehrn/LU.SB-Cuotrpeonrahtoef/3tM//UUSS-Corpor@a3tMe-C/o3rpMoIraUtSe `PSauuelLTiaednear/kUaS-/CUorSp-orCaoter/p3MoUrS @a@3t3M-eMC-/oCr3oprMopor/raUatteSe Ka`tDehaynnTahJo.mLpussobnk/eUrS/-USC-oCroproproartaet/e3/M3UWSUS @3M-Corporate `Subject: PFOS Levels from rats exposed to POSF via inhalation T-7098.3
Andrew and Tommie:
The 1 to following
1r0e0sueltss tarie mbfaoasrettdheeonsetrhuemrlaetvseelrsuomf
PFOS being
dwilausterdig1h:t1o0n0tparrigoertt.o
eTxhteraction.
`The The
eExAtrwacatsiotnrawnassfecrarrerditeod
aouctleatanpHpo3l.y0pruospiynlgenaesitnugbleeasnhdakbeloowunt
iton
dEtrhyynlesAscetuastien.g
naintdro7g5en%g1as0.mTmheamremsounltiauntmraecseitdautee.waOsf rtehi-sdissosloultvieodn i2n01u0l0uwle.roef i2nj5e%ctaecdetoonntiotr8ile
`fBleotwasrialtCe1w8asremvaeirnsteadipnehdasaet 0H.P5LmiCimcionl.umAng(r5a0dixe2ntmfml,owofmiaccertoonnitpraritliecwleassizues)e.dTthoe
l`aucteteontihtreilceoomvpeoru5n.d5smionfuitnetse.resRtesttaurtritnnog winiittihal1o5p%eraacteitoonnailtrpialreaamnedteernsdainndg wciothlu6m5n%
`equillration requires and additional 2.5 minutes for a run time cycle of 8.0 minutes
por run.
T3.h0ekMVSpowtaenstioaplearpaptleidedinothteheElseocutrrcoeS.prTahyenmeegtathiovde uisoneidzawtaiosnamnodMeSwMitSh maectohnosdtant involving the transition ofthefollowing ions:
Compound Q:2 Offset Voltage
Base Peak
MS/MS lon
60 volts Internal Standard (PFHS) 299 amu
80amu
60 volts PFOS
499 amu
80amu
Tcahlecuclaaptiilolnasrywheeraetebrawsaeds
ohneltdheatMaSc/oMnsStiaonnt
r3a0t0iodnsegbreetewseCe.n
All the
qcuoanmtpiotautnidveof
interest
((PPFbO)S1)0.a2n5d0 tnhge/imnLte(mpapbl)s.taAndqauarddr(aPtiFcHSc)u.rvTehfiet wsatasnduasreddcwuirtvhethreansgteadndfarrodmv5aluneg./mL.
weighted 1/X . This curve fit produced an R squared value of 0.9935.
1 e--
= Fai EaSoa T;7098.4. Acute InhalationToxicokinetic.StudyofPerfluooctanesaifo | Fluoride(POSF) 19
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