Document NEmjQxXk64nXavyLjG9856YZV
EERIE Corporate Occupadonsl Medicine 3M Cer Building 220-3W.05 51733 906 Fox
nRa96-0YTY
aM 6O.ccAunpaEtpiiodneamlioElxopgoiscurIenvteostPiegraftliuoonroofocRteapnrooidcuAcctiidve Hormones in Men with
"This published paper by Olsen et al (J Occup Env Med 1998;40:614-622) further examined the observation initially reported by Gilliland in his doctoral thesis that serum PFOA levels (as measured by total organic fluorine) may be associated with reproductive hormone changes. In 1993 and 1995, the luorochemical medical surveillance program had 111 and 80 male production workers (Cottage Grove, MN) voluntarily participate. Unlike the 1990 program which analyzed for serum total organic fluorine, serum PFOA was measured in 1993 and 1995 by mass spectrometry methods. Serum PFOA levels were then compared to several reproductive hormones. Serum PFOA was not significantly associated with estradiolo testosterone. A 10% increase in mean estradiol levels was observed among employees who had the highest levels of serum PFOA although this association was confounded by body mass index. Neither was PFOA consistently associated with anyof the other measured hormones
03467
614
Epidemiologic Study of Perflucrooctanoic Acid + Olsen et al
An Epidemiologic Investigation of Reproductive Hormones in Men with Occupational Exposure to Perfluorooctanoic Acid
Geary W. Olsen, DVM, PhD Frank D. Gilliland, MD, PhD
rthdou)ghvafsludorieden(iineodrngaunimionibcluoo-d years ago."* the presence o
JMeicahneMl.e MBu.rrBiusr,lMewP,HMS
fgaunoircinesaitne awacosvalfiernsttlyrebpoourtnedd ori-n
Jack S. Mandel, PhD
Jeffrey H. Mandel, MD
CLed,Fy..peCrOfLloHuo)yroaoscstauabnsmceaiqjcuoeranctcildoym(piPodFneOentAni,t-
Pefluorooctanoic acid (PFOA), a potent synthetic surfactant used in ou S677 rB41Ic fuorine fac:
dionsdeu-srterliaatledapipnlcirceaatsieosns,inishaeppaetrico,xipsaonmcerperaotliicfearcationrart,hatanhadsLreeysudlitgedceilnl iginesnpaotinet applbiceations. uracpiidlydviiesd
easdternadoimoalsleivenlslatbhorroautgorhytaheniimnadlusc.tiIonnoafddhietpiaotn,icPaFrOomAatianscereaacsteivditsy.muImn
sociates. in. aqueous solution to PFOA
p1r9o9d3ucatniodn1w9o9r5k,erwse, croesnpdeucctitveedlyt,woacnrdosss-pseceicftiicoanlalyl smteuadsieusroefd 1t1he1irasnedr8um0 oriTtnslaalbtosr,atioraybasnoirmbaelds,byPFinOgAestaicoind;,
SPuFcOhAaninefrfeelctatoicocnutrossienvehruamlraenpsr.odPuFctOiAvewhaosrmnootnessign0idfeitcaenrtmliynaeswshoecitahteerd ainnhdaliastinoont,meotrabdoelrizmeadl *~e'x*pPosFuOrAeiTMs
wmietahneessttrraaddiioolol rletveeslstowsatseroobneseirnveeditahmeroynegare'mspsltouydeye.s Awho10ha%ditnhcerheiagsheeisnt adinsdtrliibvuetredofprmiamlaerirlaytsianndthethepllaisvemra,
levelsof serum PFOA, although this association was confounded by Plasma. and kidney in female rats
body mass index. Neither was PFOA consistently associated with the ~The major touteof elimination is via
tohtahte,r
imneatshuisrepdrohdourcmtoinoens.setOtuinrg,
retshuelrtes
wperroevimdoe
sriegansiofniacbalnet
assurance
hormonal
~
\Tin
We
0d
is 8
feces. In the female
tenfoldgreter real
rat,
exc
changes associated with PFOA at the serum levels measured. Limita- fonie Comet ae
tsuibojnesctosfexthpiosseidnvaetstthiegahtiigohnestinlcelveuldse, aitnsdctrhoessl-osweecrtlieovneallsodefssiegnr,umtPhFe OfeAw 1H5EtOhAoseuroifnafreymeaxlcerertaiteon rates similar
lmaebaosruarteodr,y acnoimmpaalrestdudiweis,th those levels reported to cause effets in
Peroxisome. profiferators. like PFOA. are a diverse class of chemi-
cparlosliftehraatticonauasendheepnaztiycmepeirnodxucitsioomne.
liver hyperplasia. and. in some in-
e15FneNniioAe.biedrlptDaepg1u1es5r,G2l2=nCCuyoempsnanCyd.on1.sDPgrosa.ani.onf .EehBnor Oerfrrv,idWniodnDgOrceUawnpsvioBeouenrsesy,Dur
aSAnNdCESm:ichee.ga!tSo*carTcwiono-gyeenaersisfeiendaitnsg studies in Ce:CD BR (CD) ats at 3
A SE Pr in Nes s. icGyofaMni,nnDisV.NSPRe. pO.riam. 01a1.nSa0n-05 8. TmaLxiVmuS m amEountSoLf 3S00CpSartsPpEer
Cionp7es Oy Am6n14an53Co0l0es of Occpstonl 4 Envisamensl Mediine
daednecneomoafspanacnrdeasanaciinnacrrecaesledadeinncci--
03468
JOEM Volume 40, Number 7, July 1998
mas' and Leydig cell adeno
2mnasd."thus tPheFOiAnduicstinoont ofmutthaegseenitcu'nmoonrgsenomloosxtic.limkeelcyhaoncicsumrss stuhcrhougahs
oxidative stress.
celTl oaddeetneormmaisnewewrheetthheer rtehseultLeoyfdiagn endocrine.relted mechanism. Cook Weittahl"upga1v0agSOedmCg/Dkgraosf faomrm1o4ndiauyms Gperrefalsueorionoctsaenroautme.esAuadsiigonlifiacnadnt dien.acbrseearsveedi.n Ttheesteossttreardoinoel ilnecvreelassewmearye be due fo an induction of hepatic SareormuamtatseestaostcertoneilTvehveeildsetcmriyegah.ste bien t1h7e.arlepshual hoyfdrroexdyupcreodgecsoincvreornseion(1o7f hHiPb)ititoonanodfrotshteenCe-di1o7n2e0(vilayasthee einn.. uznyambel)e. (H0owreevpleirc,atBeitehgeelneetgaatli'veweterse. tos'tCeDrornaesasfseodci1a0ti0onp.pm PFOA fora cmraexasiemduemsuroafdio1l3 bwuetenkost tsehsotowsetderoinnewleevreelsf.ou3n*d EalmevoantgedCeDstrraadsiolfeldev3e0l0s ppm durinag 2-year bioassay, with
and hormones of a priori interest
rdersautlitc)edianssaopcoisaittioinve wniotnhlineesatrra(dqiuoal-. lpaocstiitnivaendliTneSaHr.asasnodcinaetgiaotnisvweintohnlpirno:.
ear (square roof) associations with
freAe omrorbaoluintdy stetsutdoystoefreomnep.l"oyees in the chemical division, which inicnlgusd,edftohuendPFnOoA spirgondiufcitciaonntlbyuilidn.mcroeraasleidtycaruaset-ospefcoirfitchesrtanmdaarldeizeodr dfeeamtahlse efmrpolmoyeperso.stTatheecraencewre,recfoomu-r pared with 1.97 expected (95% con. Ofindleyncoeneinetmeprvlaolye(eClh),ad 0w.o55r-k4e.d59d)i.. irnegcst.lyAinn tahsesoPcFiaOtAiopnrobdeutcwteieonnPbuFiOldA. ecxopnossiudreeredandbioplroogsitcaaellycanpclearusiwbalse wbahsiecdhosnhtohweeadniamsasolcaiantdiohnusmbaentdwaetean, PFTOhAe apnudrproesperoodfuctthiivse rheopromrotneiss. to sdeecstciroinb! tshteudrieessulftrsomfrtohme stawmoecrpolsasn-t
that were done in 1993 and 1995.
Methods
65
Sixty-eight employees participated
siinstbeodthoyfearas.meTdhiecaslurvqeuielsltainocnenaciorne-: pmuelamsounraermyentfunocftihoeni:ghts,tawnediagrhdt.. bainod-
chemical and urinalysis tests: PFOA
adsestaeyrsm.ination: and several hormone PFAOAthAenmamloysspirsay mass spectrophosteorummyPaFssOaAy wlaesveulssedinto d1e9t9e3rmainnde wa19s950.1708T0hepormaingne 1o9f93saenrdum01P0F1O1A5 ppm in 1995. The upper limit of wdehteercetaisontheirne w1a9s93nowuapsper80limpitpmo.f hdiegthelcyticoonrreilnate1d99a5.monLgevtehles68weemr-e p(lro=yee9s1,stPudi=ed 0i0n00119)9,3 Tahnedre1w9a95s salesroumhifglhuorcionrerellaetvieoln mbeeatswuereend wtoittahl sthuere1d9i9n0 1st9u9d3y(r a=nd.7t2h,ePPF=O0A.0m0e0a1-, 8n4=, P94=su0b.j0e0c0t1s), nand= i6n31s9u9b5jec(ts)=. "bTehceasuesfeinodfintghse weestriemnaottedun1e8x-petcot2ed4, month, alflfe of PFOA in hu-
and follicle-stimulating hormone
(FTShHe)?3M Company has conducted
medical surveillance of employees
e5iln1sv.o0ol0fvpesdpemriu)nmiPnoFrpgOraoAndiucpcrtfoildouunocrteiinmoepn(l.1o.yLe0eev0s--- uweesre(0100.1-t0o.5103-foplpd mgreraetpeorrttehdanfvraolm-
human sera?" Since PFOA could be
apSnoetcetenintodinoaallcrsietnxuepdyomsoaudmrueolnag1toowro,PrFkeOarAscrwowisatssh-
omCoelnnduescnetgreadugmeidnflui1onr9i9Pn0eF.O3lAevAermsporonsdgoucdtii1ou1nm5,
5rb1ai2np7gheepdnpymfl:rsotmaenx0dtar1ar0cdt2di6eovnpiaptmimoen(tm[heSaoDnd]"==) 68 ppm). I hadbeenestimated that
80%-90%of human total serum flu:
oArdijnuestilnevgelsforconpsoitsetnetdialofcoPvFarOiAat.e's
PFOA production atthisplant be-
giasnprinod1u9c4e7.d PbyFanOaewAlheci,ttreocphoewmdiecral,
process.' The productsofthis elec-
ptorrrooildnyausticestdcecdlolemfprieonauecndtdiosbn,yawritethhehigtshhtleayretfnildnu-gsmattaegreiaplr.ocPersosd:uicstoiloantiinngvoalnvdescoanvfeorutr-.
ing the chemical to a salt slurry,
dcgorrenyavitenergsttitnhlgicktaehkleiev.soloaudnrrdyfoptraocekaxapgsioansltgu.rceTakhete,o
PFOA occurred in the drying area.
Subject Selection
apterGhfeionsremrpealdlantb.mieedTninhcieaarllelywsfeuorrrveeeiml1lp11alnocymeeaelises employees in 1993 and 80 male em-
ployees in 1995 who participated in
minegd.icaanld ssuerrvuemilPlaFncOeA. dheotremrmoinneatiteosnt.-
HOTMOne Assays
theSeUrniuvmerssaitmyploefsMwiennreesoatnaa'lsyzEenddboy-
crinology Laboratory (Minneapolis,
eEMrlNeen)vceenorhLotahrbemoorEnantedoosrcyrwienr(eeTaaSrsczsaianeyane,cde:CRcAeofr)-(tiDsoHl,EAdeSh)y.droeesptiraanddirolo,steFrSonHe, sul1f7aat-e
hydroxyprogesterone (17-HP). free
pmterosontloaescttei(rno.TnSetH,h)ytrotoaainldd-tsetssitemoxusltaehtrioonnreg,mohLonHre.:
SSbiHyndBiGonfgwMegrileombsaulnoiaunlysz(seSdHEBanGtd)to.hceriUAnlrolilvoebgruy-t
rLeasbCcooerrnatcitseoorlyp.owlaarsizaastsioany.ediumsmiunngoaasfsuaoy(Abbott TDx. North Chicago. IL).
Radioimmunoassays (RIA) were
Musoendicaf,or CAD)H.EAevSira(diPoalnte(xm.odSiafinetda
02469
616
Epidemiologic Study of Perfluorooctancic Acid + Olsen et al
Pantex). 17-HP (modified CIS) and
smi
En ra
CmiRn"ed Foweigesrqueirmwndidsers:
wLHi.ngFaSHmiacnrodpaprrtoilcalceinenwzeyrmeeaiamymeud
nteoramsisnaeyd(uAsbibnogtta cmhoe.miuTmSiHnewsacsendcee.
JiumamnunCoampeitsriacno,assCaAy).(NiScHhoBlsG, wSaasn
assessed via a radioimmunoassaay f-
tetironch(rEonmdaotcorgirnaephiScciseanmcpeleRePfUeRrfeinccae:
Lcaablocrualtaotreyd).3sBotoutnald t(eesstioosstieerroonnee Wleasss fwreeree tuessteodstefroorneb.othTh1e99s3amaendas1s9a9y5s analyses.
comparing parameter estimates, using Results
dear i . Serum PFOA levels were not
sho ekSly el ver aaed LLTT LS
byshesASSyem SCS EIS TES Whingeesdbiedtnweoetn tehexamtiwnoe ehxoarmmionnee 1L16L 03 and 1D 995 dL t, resEpectCive,ly.
i(0eofP"FPFOOA.A(aapppprrooxiimmaaitellyy wtwoo 1er5e0theFfoll0owin0g: a5ge C(22,14()0:)
omens Sincehe sie rhe in hormones,Sincetheresufolrttshe
both years were similar to those ob-
Tog DueoS (13, 12, suadiol Cigarettes (0S, .11); cortisol (07.
(12,15); FSH (=.12, --.13); 17-HP
riepsaulqt ffoorrthaellenetmiprelosywedeys, aornelyprteh-e ((0141.,30=).;04L);H (S=H.0B6G, 1(3=).;07p,rola0c3t)i;n
senyeq below,
bound testosterone (01, 02); free
Ju
Semel Lh. Data Analysis Simandpsalied analyses, anal
Cytsoimsieloafaiovnalricaonewcffeeics(iteAnoNtsOn,VAawn)de. oPrwedaeirnrsaorony
value associations between PFOA
BME[:
[3
.
.
puoatiefnitieadlancaolnyfsoeusn,deimnpglovyaereasbwese.redFiocr WFFR
pvoidme.d i1n1t-o<1f0ouprpPmF.O1A0-ca<t3e0gorpipems,: 0a-n1d foA
230 ppm in odertocetrmine ifan
ee
elefvfeelcst. eFxoisrtemdulaitvatrhiesblhiegheevsatlusateirounm, LEWE
PalFcOohAo.l augsee,. baonddy cmaasrseitndeuxse(BwMeIr)e,
e19t95o.
etxinaumoiunsevdaraisabbleost.h Acaltceoghoorlicuasleanwdacsoann-- rs
--
adlryizneksdapselredsasyt.hwandn| odrninrkepesrpdaoytn.ost1-he3e
.
equesitionsnaireiieterm. cCiagmareettoe uste wa8s. fofer ct, . .
inotnesdmwaietrh.PFReOgAreesnitoenredm3adea scownetirne i Lo Sel.
uous variable. usinglinear.square,and
saqsusaurree rotohtattraansssfoocrimaattiioonnssinwoerrdeerntoot imiossned.ofTheesrpaodsisoilb.lefnroenlitneesatrosatseroocnie-,
ES
wpe :
aNnodnlbioneuanrd dtoesset-orsetesrpoonnesweasreelvaatliuoantsehidp.s were examined by model fit and BY
Tew % sw srox=ippe) mw ww wom ilFii. 1r. pScmnfuo poamolfnseesu c1s99r33(0 y195l5. by perforce cid (PFOA, in prs per
03470
JOEM + Volume 40, Number 7 July 1658
or
us
highest cago for boi sears
nein
Second. the =30-ppm PFOA cate
- Ie
.
1| | hgDi oeiryetShiaaedleeotmhmneoyarPouoFsnngOcegrstccoTapmlreeotadponencoemi-in
i
I
=uL.LTe.
.
.
mcw19eee9r5en.nngFoDorEunrOStehNi,3nlme0eevaeparnsodemstGrPcadEiuiOoleNflryevooberel:..s
edf .e
SoPonFteOesA 0hvademtesagnFhonrhatnlhrlhweeveolnro
5
rr SGndonimnePisib nveentlso haewterschso aiPboFneOenA
or
he 230ppm PFOA group 1 btn
os
er abr for cots. HERS, years. No significant associations
ad
FSH, LH, and SHBG (data not
Ny
2.
i. PELL
x
.
Hi
.
.
iT: O..
.
.
Setsn ss oyOr9 .iq Coowomomom
Ra TT"
TMTM
hctsP)sossesro1 a(nn0de92 0re sacnadtTerSpHos(0f5o,r EcsnoauarnSai ieeeeanseaoerwviTeogeeensiofnoner iE PRONae tooidcxnscooantsmmaeoTnnes any hormoosne aond conlhy one=in11090965,: eP= n003dK ai=LSe06Ta).oTohnoimfsr1eo9sfT8u1lwnt08idw8am.,s Tran I fogs, ht boo ves
Tw1eo9rm9e9p2(0o6reFngOA.miofofIdTePtecainodn 8i0n odfiTteaeblmeasn1edpviroevdinodvesaatntodhne,smoaeeinnm,nhmgeps: aSmhaoa2r3n0beymfsoo(.mu0Sehcvle1-f1T0PeE1O0c.A<ac3rm.. oeftvhee semp1l0oypeoems woirthesserrumpPaFtOeA. eFepaovtgenedlotihnoebnbeoerteahvanryvseeoaodrrfss.btyreFewroPnmooFsOTwaAarbnltpedyos.1f. age ence he owes snd
T sihaoAwhsny).ecxo opmecitnedn wiTesosgtBrsadM. i7ol(13w50a9s3. rB e% 0909o 13Cnda=nes epa s<tooe roonledowtoiu:hs
Ta2bprolvidees mean estradiol and
SBfreMeeInatoensddtoasgtteea,ronareespveTaclotueievseclmys.tprlaItotiefsieheosdubliydn s1o9T9m5ebwaaidthnBdsVenIrounm2i3Pn5,FOrAelleivoenlssi=y3s0.
S er (sT py oeA DD king into account potential con-
noentedwiehnPsaEOneexwpcaeewpnsforo1fs7asf4ce81:rm Ahgeai1n,99fhiaes aysnuepsccimaGpiioaynenswatdsisdsehcpeoons: cheaBpeeecasuste sa pyrimwaireywhhyeporesPsEOoNf itontceefanserhdi.opn cweutrneapeiascn adeescnroepinoerd dmmoad.elPsTMFOwithwaosur no1n993sgamncdan19l9y5 i(astsGeooscoonidavetres odvnwsintohf.seba Trouu(omnodrnestouwraoton dieonolro.wofnrne)e between PFOA 57d roeun monk
03471
o18
EpideStmudyiofoPerlfluocrogoctianoclcAcid + Olseetanl
TABL1E Mean, Median,
Standard
Deviation
(SD)
of
Mean
and
Range
Values by Serum PFOA Levels, and Year of Dat1a99C3olDlaecttaion"
PFOA (ppm) PFoOmAc"om) 101--<<1300
2%
Mean Medan SO o3u3s4t 204070 022117 016120600 G1a5d4s0 234301% F-25925, = 00001
Ageobcrt)
as 0 92
101--<<1300
3328 w3o5 7472
=
F=32637,p = 001328 14
Alcoohsotl Grnksiday)
04
03 0s
101--<<1300
o0r9
0057 00s7
230
F=03095.p-000 07 08
BMo-g<tm)
200 2s az
110--<<1300
220081 238 2158
=
F218605. =01924 16
Gigoacettes (cigaretiewday) 26
00 75
101--<<1300
6205
0000 17015
2%
Fe15206.p=02 00 100
Est0rasditol om) 1-<10
556407 5500 1w2s0
10=-%0<30
652488 200 1864
Fe054,p = 086
17:o4c8t(r/c)
1068 1060 M9
101-<<t300
1s27092 1108555 a2t8s4
=)
Fe1125655.p =02120 668
Proloa-c<ttin (ug) 1-<10
8I2
8800 3458
1203-<30
175s00 s7os sozs
ound testosterone (n/a) Fa37.p =001
1-o-<<1t0
029877 5s1o3z7 11678820
102-0<30
aSs6925 a5r6s5 a8196
-
Fe=24e8.rp = 007
of Peruorooctancic Acid (PFOA), Demographic
1996 Data Range Moan Medan SO
010050-08s9 033m1 2002 01%8 J1I1K8-002100000 Sa5t96 412443 26390
FaT75=700,00P1
22700e-00 442103 aw0o 883s 2Mo044s00 438.12 300 9724
Fe088=.04P8
o0o0134s
00s5
0043 0osr
000&220
0085
0047 0076
F=03=,04p3
w21s6w%o5 u2e6 a2r8s 3442 2281%320 22788 a079 a108
Fe077.P=082
000-04000 32s6
0000 6804
0000220000 0510
0000 18592
Fe126.p=030
Moo-ws0 eeasr2 s200 11479 0s7o0m0o F=emn2t060=,05P867550 6917
44450022003000 1811088 0S5450 362 s5e400-210a6400 11120330 1s0s2s0 754775
Feterp ots
z20o1m8o0 1M0e8 01000 s810 1s0o8s0o 19209 w5o0 2573
F=086.p=058 22i2029z--1i0c5e0t5e S53e4r8 sS6i4s3 11550243 W450o9-e64s4 Ss6si7d8 5629370 11855550
F=026=.08P5
and Hormonal
Range 01100-8%20 21003-0-12482100 2200868000 237000855000 000021ss 00002114 221183-48532 28122334s8 0000-240000 0000-24000 445500990600 8S400-78100 52400-1107900 472600-21937800 540022800 130024100 22718674--180358845 23048117-78023308
03472
JOM + Volume 40, Number 7, July 1088
oo
eComnins
nsowe
osm
T Ro PFOApom) e owren e iowdsmn sa0 oe mereas owwzn ee wdon a82 asirasmnsee
pj5eril
nwwWooowmoomoonnooaoadwEhMowwwWooowww nfon ooEmnm
Tnsiym)
rToneon
Fp mon
wo 1 es emus wis os aes
j5% d
fedBnhopoeoomBnowoon owamn JowaIo,nanaoonn
TG Sea o soaoatVooaTtA SS8h A ane TO rae rao ma
a Ee on e ry oo werseemrr<ot0o.sropom<. 0) 0ha3npirDev32a3 pPFnOaA on1-o43e0pm PEONct
aerisendan,SoStmanPcaFrsOELroorv(6a)nofvMeemaonfDaontdaRGanegiofnEstadio byBody Mass Index an Fre Tstostoransby Ae,
IpuI cai eoaedr Tmn r a5 he ens aa em edn SE Fargses
aToyrtem roi
D0E ommeB0G0Bi17 woeomwwsms mBov usoboR wOmo0EY322 awatommm
Iao rrn tin
Tm om nos fw ow ono nBOSmEo RmDo 32s mMeesmmeo Bwom mmis mmoo 532 ssoemmo
[ioid
TPooEgEoE onu oBomm fbooma m Eo o Eoanom
enon
w ws ws ao wsai ow ws wa on meas
a5imd Com
ToRl DMls ho owwoRmmn obo w m ow ukd oREhan me ne os mzz aw me on ssw
=oersl
SDTooomEmo
oomm
ooou%woeeoaeaeEEn
BNooEmm omoowm
on 8
mEneme
moderate drinkers. as waspreviously
reported.TM
DisWceuscsioon ntdwourcos tsecetitonadaml
10 investigate he ein beeen expandeososl,umearneest rseorudm uPcFOAhorlemvoenlessanidn spevaerriaclorle,- edimoplloleyveeelss wweireh 1t0he% hgirgehaetsetr asmeornug.m poewssetiria4dv1ie0olasnasrnodccitahetrsitooosntbe3reotnweS.egenAnilctPhaFonOulgAyh ~~aiPnFsyOAiwaslnevcerolsnpf(ou3rn0ideedplpaibmmy)it:teBdhiMboIwy,oetvaenhnred.
03473
eo Gfielwlilsaunbdjeacltso oatbsethrivxedPaFnOAapplreovxeli.lmeavteels1f0r%ominhcirsealsoeweisntm(e0a-n1 epxpramd)iotlo ghiagnhiecstu(o1r5i-n2e6 plpevme)lstoatamlosnegrutmheosrepprreosdeuncttiosntudeym.plthoiyseeprse.viUonuslikreepotrhte paolssiotoivbeseravsseodciasaitigonnifibceatnwteenonnleisnieraa-r idinole.anPdostsoitballe sreerausmonsorfgoarnitchefldiufo(f1e)renutseroefsudlitffeirnecnltudmeeatsheurfeomlelnotwisngo:f feixnpeosiunre19(o9t0alansdersuemruomrgaPniFcOAfluoi-n t1h9at93thaendmul1t9i9v5a)r;ia(t2e) mtohedeplosusisbeidlitiyn `1m9o9s0cedmaasytichiatvyeastsraunmspgtrieosnsoedf rtheegrheos-ssiifoincaatniaolnysoifs'c:o(n3f)opuonsdsiinbglevmairsicalbalse-s t(ewge.entheBMeIxpeacntdedestrrealdaitoilonswhaisp nboetofibcsieerntved= in0119;90; (4c)omdcilfafteireonnt csouebf-jiepcattsedanianlybzoetdh t(h9e4 oermipglionaylee1s99p0artaincdethmepl1o9y9e3essuwrvheoysp,acriocmippaarteedd iwnit1h96910 easntdra1di9o9l5)a;ssaanyds.(5)differences in the senDsoitsiev.ittyhrmeashyoladcecfofeucntt, afonrdstpheeciaep-s mpaalreannddihffuemraenncesstudbieets.weeWne tdhied annoitotbwseeernveesatrsaidginoilfiacanndt PasFsoOcAiatbiuotn dbiedsoebrsuemrvlaeeve1ls0%ofiPFnOAc.arStetreheumhaiPgsFheOesAt thineotbhseesrevawborlkeeerfsfecwtaslevleilkseilny abneilmoawl sttuhedieCsD: threatobissesrvoambelweheefrfeectalbeovveel ian PmFeOaA.n" Aselrulm bluetvetlhreeofPF5O5A mpepamsstuurdeymenwtesrefrboemlowemp5l5oypepems PinFOoAu.r lTehveels10o%bsienrcvreedaseaminonmgeanemepsltoraydeieosl PWiFtOhAth(e23h0ighpepsmt)lcevoeullsd osfuggseesrtuma tthherecsohnolvderrgeesnpocneseo.f pTehreoxdiissocmoavlerpyroo-f tlhiefierratnourcsleaanrd heostrrmaodinoel artectehpetolresveplroo-f
Epidemiologic Study of Perfluorooctanoic Acid + Olsenetal
pvoisdseisblae ptlharuesisbhloeldmreeclhaatinoinssmhipforbe:a Wthwieleen rPeFpOoAseatndpeersotxriadsioomle "pro7sleirfvereadtori.n lriaktes PaOndA.micaere.reoatdhielrysopbe-schioewsn--innoclsuudcihngresphounmseasnsto--hmaavney etqyupievsaloefntpedroosxeisloevmeels.pr+ol!iferlors at assWoceiadtiidonnsotbeotbsweerevnePaFnyOsiAgnainfdicfarnete doirdboobusnedrvteesatossitgenriofniec.anHtopwoesvieirv,e awsesociation between I7-HP and PFOA. Winetheexa1m9i9n5edbu1t n7ot -a19p9rH3ecPaunrasl.yosreso.f steusgtgoesstteerodnet,hatbePcFaOusAe mCaoyokaffeetctatlh'e vcioanvienrhsiiboitnioonf o1f7-1H7,P20t-olytaesset.osItfertohnies reenszulytmwe waosbieunahinbiiltnecdr,edatshee ienxp1e7c-tHePd yleevaerlss",swtuhdiicesh, waaltshooubgshersviegdnifiincabnottlhy inonlythe 1995 study. Recent labobreatoarny awcocrokmmsoudggaetsitosn tbhayt tthheerCeDmarayt e(f0fetchte oifnitPiFalOAt.es"tosAterporneev-iloouwserirnegtpivoe rnoonlbisneeravred asasosciigantiifoincanbtetnweegeanbtootualndsteerstuomstefrlounoer.iTnehisanodbsefrrveaetioonr dwaatsa dpoeipnetn,dtehnttoufpoann eonmeploinyfelueenwtihaol fhlaudornionedelteevcetlabbultehtaodtatlhseehruimgohrgeafnsriect.e tesSteovsetreraolnemleetvehlodmoelasougriecda.l issues tshheourledsulbtes fcroonsmidtheirsedstwidny.evFailrsuta.tithneg fcroasosd-isrerectcitonaanlaldyessiisgonfdtohees tneomtpaolrlaolwhitaylofflaifneaosfsocPiFaOtiAo.n.itGiivs ecnontcheeivlaobnlge athcactomtmheordeatmiaoyn beto stohmee ebfifoelcotgsicaolf aPl."FOSAe.conasd.sutghgeesttweod crboyss-Bsieecgteilonaclt paneanldyesnets pcoapnunloattiobnes vbieecwaeudseas68inedme-Fpleowyeeresemwpelroeyesetsudipeadricinipbaottehd yienarsse.. sreusmsmmeneta.suarletmheonutgsh itnhethmeajo1r9i9t5y aos.f
ethxopsoesuwriethletvheels hiingh1es9t93searlsuom pParFtOciAspiazteedriensul19t9e5d. Tinh'islorweedrucesdtatsiasmtipclael uporweedr. seThriurmd, PwFeOAspelceivfeilsc.allyUsmeeao-f total serum organic fluorine may repcroesuelndt obteherpepreorxfliusoormoecarpbroolnisf.erwahtoircsh, walotuhlodugrheprdeasteant stuhgegegsrteattehsatt frPacFtOioAn oifntotthailsseermupmloorygeea.nicpofpluuloartiineonle'v=el*s eFroruorrtihn tihmeproertcaonutldcobnefomuenadsiunrgemvaernitawbhleos. pAanratliycsiipsateodf tihne b6o8thsubyjeeacrtss fsohuonwdeidnggofoadctcoorrsreolfatBioMnfIor(trh=eco93n, aspe=cts0o.f00a0l1c)ohaonldcothnesusmepltfi-orenpo(r7te=d i6ng7P(.r ==804..P =a0n0d.0c00i0g1a)r0.etiFei1fsthm,)otkhecquaanlibtey eovfalmueadtiecdalbysuwrhveeitlhlearnckendoawtna associations are observed. In this preecgatredd,aswsoeciaotbisoensrv(eedg. evsatrriaodiuosl aenxdnBaMllIy,. tfrheeeputlessattoislteenraotnuereaonfdsaogem).eFoi-f ttheesthosotremroonnee)s hsatsudireedsu(lctge,dFSinH,prLiHo,r mreocnoemmmeenadsautrieomnesntsthasthoumledanbehotrh-e sreasmupllteosftpaokoelnedatbslhooordt ifnrtoemrvmaulltsi.pIlne foeuarsisbtluedyb.ecmualutsieplofetshaemplloewspwreorbaebinlo-t tithyreoef seammpplloeyseeosvevorluanta4r5i-ly tgoiv6i0n-g minInutesutmimmaerpye.riowd.e conducted two c1r9o9s5s-saencdtidoindalnosttuodibesserivne 1a9s9i3gnainfdi PcaFnOlAy peoxspiotsiuvereasasnodciaetsitornadiboeltwoerena wsiitghnitfeisctaonsdtleyronnee.gOatuirvestuadsysomcaiyatinoont whahveethbeerenasnensaistisvoecieantoiuognh btoetdweteeecnt hPuFmOaAnsanbdeceasutsraediomleacsouurleddexsisetruimn oPbFsOerAvablelveelesffewcetrelevleilkselsyugbgeelsotwedthien vthiedeanriemaaslonastbuldeiesa.ssuOruarncreesutlhtast psriog--
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sificant hormronail cnhangeesmplaomyoenrgs 1 HYN. iElbmsVinnod Mc. KteoAf eKarma 37. HUelthFAo. oSforepmnonwSaDt.erReussh dDiEo
were non sparen in elton tothe (SII TL eS
measured serum PFOA levels.
Acke nowlnedgmsenotys soon
15. TTeohadeviscomlTd.oc1A9i8oi7n:6Ko1.:f6F6pu-eb6s8oo.dxsnoK.meTngsolkfaerMs.: 0 1 ot cr ty nnd ory
28. Gahioll.ltil,a(nDdoScFntDa.okre!FslduinnirsaonecOarrcabcioonusneatMniidamHelusmpCaeon-. i MN. Uner of Maes: 152
oesuber rally skreoyulFhoe,
us. a
=mesbolcaillhy ne,n
dSaImeRsTof
25, ePoeiadpraadds V.eSomdioumfosbpvhnenny
`MarryyHHoamnseen. anndd DDrrss JJaamsesPJRohnOsoBn.SRoger = ace o TP Lecn KP. Per r MA. Gileso`jbol ungd fluorminaerinso.rganviaclcoCmhepno. u1na9dn8sd
Re1feyreeneHc.eIsndus and ilian apes
iensduoced. ahmempoatnoimuemgalpyerahnodorpoeorcoaxinseosmee.. postion. Exp Mol Paths 95747.
30. sGsianpeR gaduFiD,onMaanndey J15.OcMcorMaeld
oF hoivcehnetm. NIena.Siomron1Acesd.. odemie c Pres: e19n612e97-d4a92.foe dam ta
17.
8S-i1n0a9i.LJ. Two-Year Oral img Sut
(ofieF)loTroers.
Chemical FC.143 1 Ran SL PALMN.
3. SimovnsJ. Bnoe eTn. nElsrhoackhemFiclao Coma New York: Acemic rss
ang.
ComptiRnende. 18t5v6,4h3e3r85 sr ie hon scum,
tNaw.o
18 CMRIoiEoe.ksILJnCad.booMtroounraioeyfs,LSW1e.98d7Fracmlel sSeRnoHmsOs mm ----
5+3
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NWolerRMlIT., QsCuouanioizfycanGiEo.n
a en
rTeo.m o19i68ee 217N:o1u0t r50e-11095)6o8b0i5y58of9se.. ScowlepepnldPohcahrnmaecoel,dm19e21c1h32n0.821T7o.. Se erpounis of Homan 19. Bgel Lb. Lm RCM. Hom ME. Cook
cocnhamna uIoOnSde 1 hLWeFEseTu uEg
a oet heane a,r tCoovPenunrito..of vIeiC.cEoafftenoct,sonaofLocaxvmihmeooinsiutmfsrpoTenrouinn l LpoouetBCnoLnoontT.EPoo. WR 0 Com
RGoochtesoterF:D.197L2o.ng JE. Animal toxicity `setudimeswintdh aFmgmoAnsioucmp5erf1l9uo8r0oo4c1t5an7o6-
20.ApLpulRPOhaMr.maHcoolm. 1M9E9.5:1C3o4o:k18-J2C,5. Bigel aLBm.mEfofnecutmofethrelpoerrooxoicsnomoespreoli(Cf3e)r.atoorn.
3, PYP"R ha
.
. SSAeStsielsu.sttVee,riohune. 6.SACSayU.serNsC.GuSidAeS
583. 7. Kennedy G. Dermal toxicity of ammo-
hepatic aromatase activity in adult male CRECD BR (CD) rats. Fundam Appl
losis Inc 1900, > OAffn JE. Wikon JD. Disordersofthe
nium perfluorooctanoate. Tosicol Appl
Pharmacolt. 1ao9n85f:81:ps34a8o-3wm55.a1. CpheeinuBoL..
Toxicol. 1996:30:220-228.
21. LoPrersmobesarnagmelresT.pocDeeerspsveoarrgangcenilBvi.nageWpadahltrihewWap.y
testes. In: Isseltacker KJ, Braunwald E.
`DoWillpsMooensd.iIcDHi.neMer.oaNner'wsJtBYPi,oFranakcuieMeicsAGSro.afKwaHreiprelr
opcrcuenosnsFoodChem Teor 1986, [Iadtephysiology. Am Rev Cal Dev 35. Mongome-y DC. Pk EX. nrdactin
9. Ophaug R. SingerL. Meabolic handling of perfluorooctanoic acid in rats. Proc.
22. Cook JC. Hurt ME. Frame SR, Biegel LB. Mechanisms of extrahepatic wmor
10 Linear Regression Analsis. New York: John Wiley and Sons. lnc.. 1992:
Soc Exp Biol Med. 1980:163:19-23. 10. YiinenM. KohoA. HanhijarvHi. Peura.
induction by peroxisome proliferators in. CC BR(CDD )rats. Toricologss. 1994;
an,
36.
Keller H.DreyerC. A. Oto K. Wahli
Media J. W. Farty
Mahfoudi acids and
P. Disposition of perfluorooctancic acid.
io Tnonthaeln ra1t99af0t3er4.os8ui6nn-g5le3EaanmdonsubCchormonmiac
14:301 (abstract).
23. JOe Cg.boPuame ncrJeDa,tiFcr.oamoenvcSoRg.eaniElcl.io1te9fGfS1e.c5Ct6so2ook5f
crheootruinagohcidvss aiceodni trroloefea lppieoprirodexn iimsneootmdaebopXlriosrtem ceptor eran.ProcNotAcedSc.
1. VingeeHeouvenlJ.KoTosieB.oVoaoniRoefnel,. 38. (RasooMcS..Reddy IK Hepaiocacinogen, ~~ 1993502160-2161
1 mceTetiaobbnooliesnm aaandd eeln1imHiBneiateoiclohneImo.f aTpecorrfoloulon-
25. AeSBsciaausdoafSwnptiethrMo1xSI9i91so318m030eW8ep5Arc7omlk3imf5eDor7aint.oitrsaa. APTnaensneN.rY wane. (CAS No. M2526, tn
37. GWHtihueennirtreRorJA.is.dKiaChsovasrapmemoonnAeJe,ec.sWpniCdonprnresosrwoiCxniJusb,oeRmnaeecpehrg.onperoxisome _prolfrsar.ccsponive
BTor man a emkn ondcsteermiucrootre,oartlesRaa19M0a1non, WI Haschon Lo. 3 Bute Toil, 1272539 36 Pe RG. Imeniogfsamimoonunm
gSenesi. Ml Cel Endocr. 1596116 3%. Sriner DA. Heputic Persone Prof
aotn meorSooopeirfLeon.Thde points
tpfooeearnduTpsorewoamlslsIpIroonSblhsoormn(ointhen jet
TcEourxtakoo.plsong[yMCoennooftgerCafhopehmENiox.cvao1n7(c]ElCoBEgTiyOClan)d To
03475
622 39. JDRe. aLagliveasniia NFDA., MSciGmuciurreaEdDiv,erHsaistykionfs
pPeermoxaimsmoamelipnrivler cielflas enndnvhiveioi.roeAfmrfneNstYs 40. ATcugawoSoc.d I1D9.9A6:l8d0r4i:d3g1e0T-3C2.7.Lambe KG.
pMrolafercstoDr-Nso,ctWinovaoeaddy.lanreNdcJep.toPres:roxsitsroumce ures and. foncion. Amn NY Acad Sc.
EpidemiologicStudyof PerfluoroAcoicd tOalsnenoeltacl
41. T19u9g7w:o30o4d:25J2D-.265L.ambe KG. Woodatt NpeIroIxnicsroimnedpirvoilduiaflriafoerracetnicveasteidn hruecmeapnooprina.lp1h9a9s7i:c36t:u2r3e6 a(nsdbsfiucntt)i.on, Toco
42. OGuldemnunGdWs.en KSuLs.cChurGiDe. MSFt.aTfohredpoBAs. ive known association design: 3 quality
saurvesillsanmceeudtahaor.dfJoOarcoccncuuppMcaetdi.eon1s99h1e.a3l3t:h 43. G5o9l8d.i1e0h0e0r IW, Deer TS. Smith KD.
Setlesibnibletrygerof.raIpidmlypNurctthaoetivdnigignplnoassgimca shaomrpmloinneg lteevcehlnsiqubeys.opJimCliiznedEnmduolcirpilneo-l Metab, 1976:43824-830.
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