Document Qg91obqpGNmJx525QD46J48yR
L226" 1725
reper
Final Report
T-6295.28: Analysis of Liver Enzymes, Glycogen, and Perfluorooctane Sulfonate (PFOS) Concentration in
Samples from T-6295.25: One-Generation Reproduction Study of PFOS -- Mevalonic Acid/Cholesterol challenge and NOEL Investigation in
Rats.
Study Location:
Southern Research Institute (SRI),
P.0.
Box 55305, 2000
Birmingham, AL
Ninth Ave South
35255-5305
Study Monitors:
3M
John L. Butenhoff, Ph.D., CIH, DABT,
Medical Dept. / Corporate Toxicology &
Staff Scientist
Regulatory Services
3M CSeanitnterPaBuuli,ldMiNng 5252104-42E-02
Ph.: 651-733-1962, FAX: 651-733-1773
&
Deanna J. Luebker, M.S., Senior Toxicologist
3M Medical Dept. / Corporate Toxicology & Regulatory Services
-
3M Center, Building 220-2E-02
Saint Paul, MN 55144
Ph: 651-737-1374 FAX: 651-733-1773
Sponsored by 3M Specialty Chemicals Division
3M Center Bldg 236
St. Paul, MN 55144
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Page 1 of 13
Study Objective
Final6R2e9p5o2r8t
a(hmGeo6PuoDnb)tj,eocfmtaiglvlieyccooefgntezhniysmaesn,tduadPynFdwOaUSDsPit-nogllmiuevceaursrsuoprneeocstiyhmleetarncastnicsvofiletlyreaocstfeegd(lfuUrcDooPmseGP-T6F)-OpSahnodtsrptehoaattdeeedtdreaerthmdyidnreotgheenase
pups.
ams and their
Methods Summary
d1Te:2th.aei1li.en6d,-iiofnret2ph.oe0rftmiignoa/nlkorgfepPhoeirrstflosutrourdtohyoact(tTsa-tn6ued2y9S.5u.l2fB5ro)ineifwclayAs,cifpdee,mrafPlooertmareasdtssiawut meArrSegaludtso(srPeedFsOewaSir)tchhfo0lr.a04b,o2r0ad4ta,oyr0si.e8ps,ria1n0d, is 1gm0eastdteialntiigvoewnriydthaaynudn(tGarlDel)artee2dm1aboirrneilenadcgetradtmaiamolnsedswa,eyrthe(rLaoDlu)lgoh4.wceodSnetfloiecrlitmtetddammastwinegre(asamcarixfiicmeudnonofG1D4 2d1ayjsu)s,tapnrodiror gLrDoSuplsivweerrseamapnlaelyszferdoimn dtahenscuarrnedntpusptusdy(.pooDleetdaiblys alintdteerrr)e,siaunlnttdshesoaf0c.rt0ih,fei0cP.e4Rd,Ow1S.i6t,ahnaatnhldeyis2ri.sp0uamprges/ioknngclLduDodsee5d, mainenadtshDeuarTie-lde6y2u9s(5i1.n92g656C)afiCunlsa;linrpgerpetochrietp.iatnaGttlhiyronoc.noegTerhneeawgetanwsto.acnyUatlDoysPzoGeldTic,inemnpazulypimcessea,nmpzmlyaemlsei,conealnnydzbyGym6etPhaeDnmdaecGttih6voPidtDy,owfwerReeo.e NasAsDayPe:d stpoeNctAroDpPhoHtoamte3tr4i0canlml.y bTyhestmaincdarrodsolmitaelraUtuDrePmGeTthaosdssayfoflollolwoiwnegdtthheecroendvuecrtsiioonnofo4f. re bniettrwoepehnentorleaatte4d0a5ndnmconatnrdolalasnoimuaslesd asntadnadnaardlylzietdertatoudreetmeertmhiondes.staAtlilstriecsaulltdsifwfeerreencceosmpusairnegdthe students T-test
Results
(RG0e6.d4Pu,cD1t.i6o,nasndin2a.v0emrga/gkege),nzbyumtethaecsteivrietdyuwcetiroensobwseerreveodnliyn sFtOatsiastmipclalelsy astiganlifdiocasnetgirnotuhpes0a.n4aalnydzed bv1ue.t6remthgoi/sbksregerddvuoecstdeiiognnrtwohauepsFs1oanmlsypamlspetlsate(iscTaaaltbllyaellsi1mganaintfdeimcFaainlgtudirnoeste1h)e.gr2Ro.e0udpumscgta/inkoagnlsydzoiesnde,avg(er0r.o4au,gpe1s.e6a,nmzpaylnedmse2(.a0Tcatmibgvli/etkyg1), and Figure 2).
NMaolistcatEisntzicyamlley significant differencesortrends in enzyme activity were observed in the FO or FI samples (Table 1 and Figures 3 and 4).
bSUtuaDttPiascGttiiTcvailtlyyisnigtnhiefi2c.a0ntmgi/nkcrgeadsoesseignraocutpivsitaympwleersedoibdsenrovteddififnerFOfr0o.m4caonndtr1o.l6(dtoasbleeg1roaunpd sFaimgpurlees tg5)hr.eouR1pe.sd6uaacnntadiloy2nz.se0dim,ng(a/0vk.e4g,rad1go.es6,eeangnzrdoyum2p.e0saamcmgt/pivkliget)sy,(wbTeuartbeltehoibs1searrendvduecdFtiiignounrtehwea6)sF.1osnalympslteatsicaatllalylsmiagtniefrincaalntdoinse
Page20f 13
FinTa6l2R9ep5o2r8t
Glyeogen
IInnccrreeaasseeswainsFsItaltiivcearllgylsyicgongifeincacnotntaetntthewe2r.0e
observed at the mg/kg maternal
d1.o6seanldev2e.l0omngl/yk(gTadbolsee
levels. This 1 and Figure
7.
Discussion
pwGrhloiydccuhocgGeeGnfrPseDteogrllaeugvceeolsdsei.asrceaTsmheaertcykopeneddlTiyati(roGenSdDul-ce1aeadds),otroaalabsbsonenoktrn,moaiwlmnlpyaaislraivrnoggenoarGmidoeeruskntetr'sosyodifinsggelatyshcee,ogliiesveari'cnsontadbiiltiitoyntion aphnyyrdpuomvgealttyaecbeiomnliitach,epiebnrlctoruoerdab.saetWidiodtnehspooeucntcduaercnotchneattioncnuaonfautcs,omeetxaobgoelniosums, asonudrcinecorfeagsleudcolseev,elsseovferleacnhtyatpeogahlneydclievmeri,a paanliemaklisdnbeyosm, waintdhdGifSfDu-se1avaicnucolluadteiosnmaolflhbeopdaytmospciyrztoeemsainswdietehfmeatlcaaliragoteuitaocmno,omuesn.etvesrOoebflsyegrelvnyalctaoirgogenensdaapnaddlieesmiaivnlelrs, amounts of lipid
PpIenFrOtthuSerbecauxtrpirooesnnutroefs.tguldRyyec,douGgce6tnPiosDntosarciatngievaivsteiyrmaianlgdaergeolnyzctyhoamgteewnahclitecivvheiltosycwcweuerrrseewaoinbtashleyGrzvSeeDdd-tTionadFemOtaeayrnmodicnFceIuirfsuapon
ll dose suggest
tlheavtelPsFaOnaSlymzaedy.
Although act to down
nroetgualllatreedaucctitviiotnys
owfetrheissteantzisytmieca.llyInscirgneiafsiecdanFtI,
thesaemrpelsousltsat liver
msgiglgy/nckiofgigcelanenvtecloantattnehdneta2nw.a0osvmegarla/slkolgoidbnoscsereeravsleeedvewilan,stahoiwbsisdseteruvdryea.dnogvAeelrotnhcoocnuotgnrhcoeltn.htirsaitnicornesasweaswaosbsoenrlvyedstaattitsthieca1l.l6y
moMtaaalrlikceTr3eonafznTyd3mTea4catnliedovneUloDsnPolbGisvTeerr,avcewtdaivsiintuysnecwrheuarmnegsieandvm.epsltTeihsgiasftreiodndmtioctahgteaeiTsn-t6ih2ants9,i5g.ahl2tt5ihnsottuougdhdye.scirgMenaailsfieiccsainentnzdfryeecmereea,nad uinnalfefveecltsedo.f fUreDePanGdTtloteavlelTs3whearveeinbveeesntiogbasteerdvteod,dettheeramcitnieoinfofinTc3reaosnedthgelluicvuerroanpipdeaatrisontoanbed. ases tdehxeeccrrheeytapisooetnhieonsftiThsy4rtohaaintddUhToD3rPmmGoanTyeaoclcetcvievulirst.yupiTsohnienPcrrFeesOauSsletsedxoupfpootshnuirsPeaFnaOanlSdysebixesp,oraselustrpeho.onusigbhluenfcolreatrh,e doobsneortvseudpport
Conclusions
zoTachtceuarnrrdeisunmlgotusinsoeafnptihumipsaslsstbuoedrxynpoitnsodeiPdcRattOoeSPtRheOaxtSp.poesreTtdhuirdsbaammtiasoynanrodeflgsaltheyodcuoltdgoetbnheesttdhoeercarfgeoeacuspserdoocfveifsausbteiulsrietmyaionyvbesbseetrivged in UReDsuPlGtsTaalcstoivsiutgyg,easlttTho3ugachtiuvnictlyeairn,tihsemloisvetrliiskneloyt anlottetrheed cuapuosnePoFfOdeScreexapsoesdurTe3aannddtTha4t ilenvcaertleisaosnesd. observed in PFOS exposed animals.
Page3of 13
List of Figures:
Table 1: Individual Data
Figure 1: FO Glucose-6-Phosphate Dehydrogenase Activity Figure 2: FI Glucose-6-Phosphate Dehydrogenase Activity Figure 3: FO Malic Enzyme Activity Figure 4: FI Malic Enzyme Activity Figure 5: FO UDP-glucuronosyltransferase Activity Figure 6: FI UDP-glucuronosyltransferase Activity Figure 7: FI Liver Glycogen
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Signatures: Prepared By:
Deanna Luebker, 1 Study Monitor
Reviewed By:
Qh. Bilotirstf
John Butenhoff,
`Study Monitor
Ph.D.,
DABT,
CIH
A AA42
Dan Hakes Sponsor Representative
FiT.m62R9e5p.o2r8t
"sas.
Date
otfoxfeooy
Date
01/23/07
Date
Page 13 of 13
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