Document qEJw3gpq71b0oG0mrrmeL7zM

4W# FUNDAh4E?4TAL. kP4D APPLIED TOXICOLOGY 4. 9,".-976 (1984) Cholestyramine-Enhanced Fecal Eliminationof Carbon-14 inRa ts after Administrationof Ammonium (14CI Perfluorooctanoateor Potassium [14C] Perfluorooctanesuffonate JAmm D. JOHNSON,' SHEILA J. GIBSON, Am ROBERT E. OBER JtikerLa&rxones. Inc.JAf Cemer. Building270-JSLOJS.t Paa Atinnema 55144 C @or.4, =IV& gut, t Chet wm is ac prep the I 17: ce Chokummill,.-EnhancedF=W Ebainarionof Cataii-14in R= afkw Admitih=ticm of Ammonium ["QPaguoroo=noate or PotassiumMPerguonx=anoWfonatc JoHNsoN. J.0- GiawK & J- AmD OaM L E (1934@FurdanL AmL TaximL 4. 972-976.Aftera si@c intmveam don ofammonium ("Clpaduoro=anoa:e ([@4C)PF 13.3mgnw or or potassium("Cbatuaroocanesuironat(eJITVTM 3.4nwft to rm& cboksqmmung fed d&4 as a 4% mbmm in foodwas shown to thetotalcutowl4 eunainatedviafma and to decreaseliverconcentratioonf carbon-14.Rau wm feddwkuyr&mine in feedfor14 days afteradminiumtionof("f-IPFO and for 21 daviafteradmi-;stm on or I"QPFOS. Contml mu were admbduacd radial-bel duonwhemical butwac not namw withchoks. qmmine. Cbokstymmine u==ent increasedmean cumulativemrbou-14 dimin=on in ram by 9.&roldfornu admWEacmd 1'4qPFO and by 9-'-folfdorran admininovd [SOL.Iprm Afterl"c7m, a amn or4% ofthedoseofcarbon-14was inliverofchok=yraminc-u=ud mts at 14 days vcrvz7.6% incontrolrA= after["qPFOS, 11.3%or thedm was inlivaat 21 davs versus40.3% in convw r&tL Afteradmulb=aon of eitherR&WOLVXW compOU14 pbls= and sod bloodceD aLrbott-1c4oncentrationwsh.ich win ndativelylovierthan liver concenuationlv@owealsosignificantrleyducedbv cbolemyramineu=tmeal o imtocia)or X24 hr :ghad b --dosicl sial Ten r. fram c (freeat lpwi= dcom 7@ follows: ks and Z=ne The anion of perfluarooctanoicacid has been found in the serum of manufacturing plant workers (Ubel et a/.,1980).Toxicitystudies in animals have been mwned (Griffitahnd Lou& 1980). In view of the slow elimination and the presence of the compound in plant worken' serum, a mmm of enhancing clim- al..1978).Since both Perfluorooctanoicacid @@n@uorOOc-tancsuLfouic add @rL-I)azcd as saltsand existas anioa at physicilogic pH, they would be expect-ait @ COMP@iex w@h Z Choi ne m vivo. AlthousEh Pastoor el 11@(19811;-@w-p@ted@cbolesty@e in udw and ratsand found no enhanced cUm;lnnt;*In *dm aA 't'&IC7PF( :,an= ei Zd= VA*IMS nd bleo Liverwa tutu8= ination was SoUghL In addition,since both of cuton-14 with a single IWO-mg/kg o-..sc r ammonium perfluorooctanoateand potas- of cholenyramine given at 24 hr aftera 10- lphzm t sium perfluorooctanesulfonateam comrner- mg/kg oral dose of ammonium [',cI]pcr6... Y"U:r w cialproducts and intermediatesof products, the possibilitoyf affectingthe eliminationof peduorooctanesulfonate was alsoof inter=L Cholestyramine, an agent approved for use fluorooctanoate,the usual applicationOf cholerymmin, administered to enhance elimination of xenobiotics is with repeated doses. In the study reported here, we invveess- aI;',cmo;em'bousmt'; Tozwiw. - emwen tr :icountior in humans to lower cholesterolblood levels, tipted the effectof cholestyramine adminisis an anion exchange resinwhich has been tered in feed for severaldays on the rateof 'Ca"babura'0 'r used to promote fecalexcretionof the pesti- fecaleliminationof carbon-14 aftereithrra cide chlordecone (Kepone) in mts (Cohn el subtoxic intravenous dose or ammor m ["'Clperfluorooctanoat(e["CIPFO) or potdls-it To whom allcorrespondencsehouldbeaddr=wd. sium ("'Cjpcrfluorooctanesulfonat(ec14 cl- PFOS). 0272-0590/14 S3.00 C@ll 0 1964 by Uw t - V of ToaaaMe. 972 Al ftft ofmw"wnme so&&y fi@ mwr@ft Cbole Johraon, 3 Purir. 'New Pack; rnal&f,jlnjoy be P,O. 1*ctc!c Dy Coati. 141&v (Tit)7leu.S. 974 JOHNSON. 6IBSON, AND OBER is Mrs pm 0= FIC,I.C=Wadve =wed= of tota=lrbou-14 in i@,m afta sin& inuavgnow do= of potassium ("C)Pcrduoroo=ncnldfonm A*CPFM Mom dose Of ('4qPFOS-Chot=Ym=inc U=ted. 3.4 mg/kg (0);cmud 3.5mg/kg (A@ TOW ==Wativc Pcrc=UP C=UW iD6= "eU.Wam*m wea24 75.8 :t5.0.conval LOt O.S. Fic. ecotm. convo. S=ts 4 and 8% of the dose for 0 tmated and control o@ ropectively.71'c mean carbon-14 concentration of plasma and DISCUSSION The carbon-14 present in mt liverafter tigationo; ther comr Libomtory '%chromatof red blood OeUs with cb0imOramine U===t admini@on of ['4qP]FOS or 114C]PFO is if== and issipfficantllyew th= the =can concentra- probably in the form of anionl (7rbepK. of 'bilityof pt tion in controls. then compounds is <1.0.) norough invc:s,. of the lite TABLE I EFF*croF(:mouwryxwvaT"ATme,rrONCONCDMLATION BLOOD CE l AFTERA SV4GLEL%NVAVINM Dm or ParAsmu OR Ammomum ['-L-I.PMUnAXXOOCrAN"TE(aI'dCIM) OFCARSON-14 INRATLrn& PL%GAA, AMRZD ("CpmLwLwRooc-rAmmAromAm,, ([mCpF= CArbou-14conmtmdone pound is t '-tmtionof; :2 to 3 wee factthat c. Lfecalcumi: ifold sugges Tmtlncnt sroup Plas= ltedblood ceds ("QPFOS Choicayrainine-treat(e2d1days) Controls 9.4 1.6d 35.6 5.6 0.9:t 0.1d 6.9 t 0.6 0.3 t 0.1 1.8:t0.4 ['4qPFO ChOleUMmine-tMated (14days) contmis 12.1:t2.1d 22.3 :t6.2 5.1i 1.71' 14.716.8 1.81 0.7,f 4.2:t2.4 aeach ratreceived1.13mg ("q?FOS; mom dose:cholenyramine-tmtedmti.3.4 mL4cc controlmtL 3.3 MLft ;taoheparic iii4qpFo. ;-@xchange r 'benhanced i Ill4qpFo t -fftdmost :the pernuc. -thelumcu have found 6FAch mt received4.2 mg MPFO; mean dose:cboleuymmine-uraiedraLL 13.3mL/kg: controlmu .5 M&*& 'Concentrationisexpressedas ag eq ofmdialabded compound/S of daue or ml of flui(L A,o osipificantdliyfferefnrtom controvlalue(sp < 0.05). @:holarymr are very di cbloricaci. -Lures or r 976 JOHNSON. GIMN, A14D OBF-R remainingintheliverT.hisdifrc=ce ismost likelydue to small additive lossesin collection of the -any urine and fe= =mples as well as thesumb but cumulativeerroirn not CO&Iwdng for combustion rcwvcry in the many =MPICS (>95%). Since the eXperiM=. Chernkals Division3.K and thetypingofthisumuunpt b,.Yv- F.Gi-monand J.E Wam ofRikerLAboratoncm. REFER.ENCES talconditions fOr choicstyraraine4r=ted and controlmu wm identicalwith to the dOdZkg. =mpk Collection,and azwymn, the I= tbmm 100% n=vcry of cuton-14 (urine, fcom and liver)wu judged to not affem the resultsor conclusion. O"w4 the data support possible utility otcholes*Tamine in prommoemg the c-tf-T;FoNn Of oatl- and perfiuorooctane- ViYonne in hunmm ACKNOWLEDGMENTS BOYLAK 1.1. EC&L J.L- ^M GUZMIAK P.I (I978L CbokuyrA=inc Use as a new thaapmtic-appm*2 forddadomm (Kapaime)poisow@ Somm (Wag,, imVooLD.C) 1". 8934195. COMM. W- J@ BOYLAK J. J@.L%W& L V, FmM bL W. HOWRLL. J. R- AND GU=UokK P.& (1978@ Tnanom of cbkwdeww (Kepo=@) taxiery vl - Pikq,mt) mmi,&o N. B#*L I Ated 20& 243-27L - ORNWM F. D. AM L4NCL L L (19SO).Aninw r Anw. J@itHyg.A=w. 4L P6-SU PAS@ T. P, KDCUR. & W, ^M XMMMrf. G. L JiL(1993)T.he gffgcOf'dwk$*Tuminean diminadm of ammonium patuaroocanow *fammm thebloodofran wW nam- 7amwokgw 3.g2. The -itthars gmtdwiy admowkdp the rywbc:ds or Us=- F' A- SOUPWK S- D- Am ROAM D. E (1980).Healthsmm of ph= wosim c4x=d to amnwwum ["Cbaduomomnam and potassiumrmL-.@. a -imi@ A prelimiamy mporl I Amcr. hict ped P-n@21rclum by F. E Behr of C*mumcial liyg.Ame 41.584-589. 3p s .Iadepan. low- K El et ba str ha Sig an avc sig:r to 1 tho.- an* in ti achi T=Min A Zids) have Lwpreventiv kfe= in th( cmrwve lite- and phz Ltmoids in c. apmimcnts, !Orts to detf 16 retinoids lid differeni tuful (seeL Mention or fttifiecquipm. %ftnty by the imply so: imlaybe suit "TO whom al