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Aor 1
Extent and Route of Excretion of Total Carbon-14 in Pregnant Rats
After a Single Oral Dose of Ammonium 4c-perfluorooctancate
Sune 30, 1983
Conducted At:
During: Conducted bys
RSiukbesridiLaarbyoroaftoraies, Inc. St. Paul, Minnesota 55144 May to June 1961 5. 3. Gibson and 3. D. Johnson
Report by: Revieved by:
33 Re. se0.arsconfahbn, Speciaulsist Date Drug Metabolism
=Z Qisond >./-83 MGa.na3.gerC,onaDcrau,g Mpehtoabolism Date
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2
Summary
Htohremornaatle cofhaengleismindautriionng porfegcnaarbnocny-1do anfotterapopreaalr atodmicnauissetraaticohnanogfe in
mag/skign)g.le dAotse8ofor am9mdoanyisum af't4eCr-pceornfcleupotriooonc,tanfcouartepr(emgenaanntdosrea,ts 1a5nd
2 nonpregnant female rats were dosed and individual urine samples
wcearrebonc-o1l4lecctoendtenatt. 12,Ess24e,nti3a6,llyandall48ofhoutrhse pcaorsbtodno-s1e4awnadsaenlailmyizneadtefdor
via urine within 24 hours for both groups of rats. These data
Tahrues,contshiesretenits
nwoitthlipkreelvyioutsolybe raenpyortaecdcudmoutlaatifoonc
nonpregnant rats. of |4C-perfluoro-
octanoate in tissues teratology studies.
of
pregnant
rats
during
repeated
dosing
in
Introduction
rInepoartperdevitohuast sfteumdayle (r1)atsandexcirnetpeubelsissheendtiawlorlky a(l2l), ofitahdaossebeoefn
t1r4act-ipoenr.fluDourroioncgtantchaetesamweithtiimne 2p4erhiooudr,s maaflteer raitnstreaxvcerneotues oandlmyini2s0-8 of
the dose; male rats excrete 83t of the dose via urine by 36 days
dpoossetddoswei.th A1-saimmiinloacryclgoehndeexranedifcfarebroexnycleichasacibdeen(ArCeHCp)o;rtedACHfCorisrats
excreted in urine about ten tines faster for female rats than for
smatlreongrlaytsin(f3)l.uencTehde gbyendheorrmodnieffetrreeantcmeenitn; eltihmeinartatieosn ooff AeCxHcCretiison
between the sexes can be reversed by castration and treatment with
etsetrroongeen(sfem(anlaelerartast)s.)
and by ovariectomy and treatment with testosThe effects of castration, ovariectomy,
perleigmniannactyi,onoraretrenoattmeknntownw.ith Ifsexthheorermowneerse
on perfluorooctancate a shift from fairly rapid
elimination to slow elimination during pregnancy as a result of a
cbehaarnigneg ionnhotremroanteolosgtaytes,tudtiheeschianngreatsi.n
metabolism could To provide data
have a relevant
to
ptreorsantaonltogircatsassweersesmdeonstedwiwtihthammaonsiiungmle'4oCr-aplerdfolsueoroofocatmamnocnaituem
ur4icn-epewrafslumoeraosoucrteadn.cate and the rate of elimination of carbon-14 in
Methods
Ammonium 14c-perfluorcoctancate
The carbon-14 label is at the carbonyl carbon. The specific activity Dofetatihliss olfot sopfecaifmimconiaucmtiv1i4tCy-,pecrhfelmuiocraoloccthaanrcaatceteriisza0t.i5o1n,uCia/nmdg. wraasdifoocuhenmdictaolbpeursiutiytabhlaevefobreemnetraebpoolritsemd ssteupdaireast.ely (4); the material
C0208
ae Animals
SFtioaxtsdofsweiemnragel.ecoCnThdhaiertlibeoosndeyRdiwveteiogrhitnrsdaitvsriadnwugeserlde mfberrtoemdaboa2lt1i7s-8m26oc5ras99e,sd,a(fymoseranp,3r4io2rh38our9s).prTihoe to wdaotseirng.befTohree ranadtsafwteerre daolslionwge.d free access to Purina ground chow oad
Dosing Solution
Tahlseuordaoonosaiclntygzaendosaotlreuatdiiioonnme0t.wr5ai%scaaplqrlueyepoaurasneddsofbdyoiuundmdissctohollocvroiinndtgea.ianmmTo1h.ne6i2udnoKCs'Lic/n-3gp.e0sro-mllutoiron 3.58 mg/2.0 mi.
Dosing
ETsahtceeheldorasitinntgruebcasetoiilvounetdiot2nu.b0evamsflixaoedfdmisntoiolsutateir3oenmd;l itpnhltearsamtgeiaacsntsrdyiorcsiaenlglweyast(oM1o5enaomcjhegcstr'g.Ss).with a Sample Collection
atUonrdidnee3t6e-sr4an8mipnlheeosurprsweegprneoasntccdoyol.slee.cLtievdReartf,sorwlueenragec,hkikriladltneedfyr,aotman08d-1d2ab,ylsoo1da2n-wd24e,rneec2rc4o-o3pl6sl,ieecdted gfartoinoncacahndratth.e tiPslsausemaanadndplraesdmablsoaomdplceesllswerweerestoprreesparferodzebny. contrite Sample Analysis
LDoiurqpuliiedaccahstceisan1mt.pi0llenllabtyiaolniaqddusiopntegsctroaofmkenutorewirnn.eamwoeCuornuetntcioofnugntieendftfeirincnaiAleqnuscatysanowdlaasrddientaenadrmifneecdounting. Only urine samples vere measured.
Results and Discussion
wfOoefurrethpefroeusgnidnxannrtoattrsattdososbeaedndprweitghtnehantatwm.omnnioTunhnep'r`ercge-nspauenlrttfsirvoaoftrsctoahcreteaunsrchiaontween,aniantlwTyoasbilsefr1.om Tthhee
utreimnse dOfatdaosaer,e does not appear
tethxoepsrebeessteoadtnyalasdsifapfreeerrcee1nn0ct4e-o1f1i3n3tthhe(estecaonut,maull1ac0t9ai%r)vb.eona1mA4toun2it4n
huoruirnes. theIrne of carbomid
beexyltiemnniotnnapotrfeedgnealvniitmainfuaretiminaoelneboyrfatpgr,e'g\nCaT-hnputesr,rfaluttoshceoaosgcetncadonemorpaaterdeidfinfetrroaetntschee (a1i,mn2o)ruantitese1naonitdninered
dasaifynfsceectaefndtoerbryaadpisroieangcgtnliaevnicty1y7amwtga/s8kgodretdeo9csetdeady(s1)i,anftttehiersrseuceosnisceofpntoitnoonnl.pirkeelgInyn'anattoddibrteaitoasnnsyat 17
aractcsunduulraitnigonroefpepateerdfludoorsionogctainncatteerationlopglyasmsatudaineds,tissues of pregnant
IBErhuarrilnaesLaRibvCehrowB,reeRdailsntgonLaPbuorraitnoariCeosm,panWyi,laiSnt.gtoLno,uisM,assMiascshouusreit.ts.
Ssherwood Medical Industries, Inc., Deland, Florida
co 2909
"to
References
(1) JofohTnostogn}JCD:arboEnx-t1e4ntinanMdalReoutaendofFeEmxaclreetRiaotns aafntderTisasSuiengDliestIrVibuDtoisoenof PC-143'C_ (Report) January 30, 1980.
(2)
HiannhPiejrafclvuiorHo,octOapnhcauagteRHE,xcraendtiSoinngienr thL:e
The Rat.
Sex-Related Proc. Soc.
Difference Exp. Biol.
Me
171:50-55, 1982.
(3)
Janssen FW, Disposition
YionunRgatEsM,ofan1d-aRmuienloicuysclHoWh:exanEeffCeactrboofxylSiecx
Hormones on the Acid, a Metabolit
Of a Semisynthetic Penicillin. Drug Metab. Disp., 4:540-546, 1976.
(4) Behr PE, and Johnson JD: Synthesis and Characterization of re-143-"%c (Report) December 28, 1975.
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Table 1
+
Cafatrebron-a1S4iCnognlteeOnrtalofDUorsienoefoAfmmPorneginuamnta'n`dC-PNeornfplrueogronoacnttanFceamcaele Rats
Dean Dose, 15 mg/kg)
_--
Tine Interval-
Rat Identification Number
(hours)
Pregnant Rats
Nonpregnant Rats
2 4s 7x
1
6
%
0-12
92.92 88.6 92.0 93.5 91.8 87.0 69.2 781
12-24
6.8 10.5 67 52 7.3
12.2 29.6 20.9
24-36
0.2 0.7 0.9 0.8 0.7
04 10 0.7
36-48
0.1 0.3 0.5 0.5 0.4
0.4 03 0.4
_--
pwwaaitstahi1n0ar9e4.878eh2xopu3rr.es2s.)s.ed (aTshepemreacnenpterocfenttotoafl dcoasrebone-l1i4minealtiemdinavtieadurine
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BEST CORY 2;
e
Distribution List
HT. case 5. . chang G. 3. conara HE. Freier F. 0. Grittith D. P. Hagen
L. I. Harrison 3. b. Johnson E.G. Lawprecht 3. b. Lazerte We C. Mecomick Re L. Meguinn Re A. Nelson/r.C. Coyne Re E. ober
W. H. Pearlson
R. A. Prokop
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