Document NeykXJgO5Q97pxXd20ajkz83D
AvALYTICAL WoCHESSTRY 1. 116.34 (1981)
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1H, 1H,2H,2H-Perfluorodecanol to Perfluorooclanoate
DONALFD. HAGEN.* JONBELISLE.* JAMESD, JOHNSON.A ANDP. VENKATESWARLUS
"Cons *Central
Resch Re~ea~ch
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Chemicls
C~emicMs
Divito. Division.
3M Company. 3RMeceCievmederf.uSset. 16,1981 Pa~L Minnesota 6~144
Re~i~ June 16, 1981
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~ og ~e al~ol were i~lat~ from lh~ b]~ ~lasma by an extraction lec~aiqae~ ~erivatiz~
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containing metabolkes w~r ~t~d by th~ ~uorine-s~ifi ~ann~l o~ th~
of
MPD and on~ of ~h~ was s~ow~ to ~ ~rfluor~lan~te (C~F,~COO'), ~p~aran~
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ato 1hthe pres sump. ~rfluor~tanoat invoive~ dffuo~in~tion of the CF~ g~p ad~a~nt to the CH~ group
in th ~rnt ~m~und.
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pcreoa e po es iD bo ion ~ Abbreviations used: GC, gas chroma|ography; MPD, microwave plasma detector; FID, flame ionization de-
fluorinated compounds will be described in
thi"sThweodrket.ector plasma (not (0 be confused
:
Ilor,
The detector plasma (not to be confused
ans2657/81/1803360850200/0
ne
336
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11225577..00000011
3MAD0509473
3MA00509473
141421 2H PERFLUORODECANOL BIOTRANSFORMATION
3
337
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tection for each element simplifies the in-
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GC chromatogram.
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ranges
menTthse. ments.
from 0.01
improved
to 1 ng/s
separation
for various
offered by
ele-
GC
25to
25
ml/min is utilized afer the splier the microwave cavity. Makeup helium
ml/min is utilized after the splitter
toat
to
capillary columas, couped to the MPD, The improved separation offered by GC
capillary columns, coupled to the MPD,
11225577..00000022
MA0009474
3MA00509474
338
HAGEN ET AL.
PLOTTER
COMPUTER
(F,Oj
=
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Er (MPD) I I
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~ =| ~TOMULTIPLfERS
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FIG. I. SChematic diaRrarn of the GC/MPD-Sh0 data system. FID, I~ame ionization detector; and
'L
MPD. microwave pLasma detector. Spectra] line~ of up to eight different ele~n~ c~n be monitor~
~imuhancousty ~a the dat~
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calculating elemental ratios (C/F, C/H) in Purina Company, St. Louis, Mo.) and water
addition to specific element detection. A cap- immediately after dosing with a single oral
illary system was briefly evaluated for the dose. The IH, IH,2H,2H-perfluorodecanol
characterization of the plasma extracts, in (Hoechst, Frankfurl, W. Germany) was an-
this case, a Hewlett-Packard 5840 chro- alyzed to ensure its suitability for biotrans-
matograph equipped with a 30-m fused silica formation studies and found to contain less
methyl silicone capillary column (J and W than I ppm peffluorooctanoate and less than
electroncapturedetector was employeTdh.e Scientific, Rancho Cordova, Calif.) with an
electron-capture detctor was employed. The
alcohol wassuspended in 100 ml of pure 5 ppm inorganic fluoride. Eight grams of the
alcohol was suspended in 100 ml of pure
|
temperature program was 50=C for I rain,
t`htheenn 22CC//mmiinn ffoorr 1155 mmiinn,, aanndd 2200CC/r/aminittnoo
280C. A 2-~1 sample injection was utilized
Mazola corn oil. The mixture was resus-
ppcennddeedd wwiitthh a@ ttiissssuuee hhoommooggeenniizzeerr bbeeffoorree each dose to assure homogeneity.
with a 70/1 split ratio.
The rats were weighed immediately before
Animal dosing and sample collection. dosing. The volume of the alcohol-corn oil
Thirty male Charles River CD rats (Charles River Breeding Lab., Wilmington, Mass.),
suspension used was calculated to give an alcohol dosage of 400 mg/kg ,and that vol-
9 we ks old, were divided into groups of three (nine test groups and one control group). The rats were conditioned for 24 h
ume was administered to each rat with a 2-
ml glass syringe fitted with a stainlcss-st~ l intubation tube. Groups of three rats w~re
to individual metal metabolism cages with sacrificed by exsanguination at 1, 2, 6, 12,
free access to water and fasted overnight prior to dosing. The rats were allowed fre
24, 48, 96, 144, and 480 h postdosag. The
rats were anesthetized with diethyl ether and
11225577..00000033
3MA00509475
IHN IHPERFLUORODECANOL BIOTRANSFORMATION 3 IH, IH,2H.2H-PEKFLUORODECANOL BIOTRANSFORMATION
339
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with one ether rinse of the 10-rot tube.
stuarmep.le was analyzed via GC/elction sample was analyzed via GC/electron
cap-This
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Tower
SBpbeiiloipoclagaoribgacliteeaealtlopussmbaalmmiicpcprlaoleetdssi,e,otnewwiriblmllylinbboaeenteittohhnoeefosstfuuhfbbeljujeeoaccurttitnhooefofrinaas dccmroooennpttthpeeaennntrtsse0wwr3eeearr1gee-emnttlrrtaaRnnaessdaffdceeterridrr-e.eVddiAawwlfiti(etthPrhe5rtthchereeai1ppn3ll,a2as2stth1iiec)c
(s(pPel5ep.2aVw)raa..s)t.ecOOarprlguguabalnlnaiicitccaetfRdilouunbooyrribinsyneubopptnrrreeeassceeotnnfittnitgihnneittnhhaoeerusgtsahaanommirc:s.- dsaanranomddppplbbeerrrootuuwoggahhasttla-t(mno0all11Ry00ze00eadcygtlliw-Vifftirinhaaalllt(Phv~eoielorGulcumemCe.e/1.3MT2TPh2hi1Diss)
pRflluueoEorxwriitddareesaccfftraroilocommunlttahhtpeeerdottcoobettdyaaullrsfeufll.buuootrrraiiTnncehet.ie.ng
inorganic
extraction
sysiem sample was analyzed with the GC/MPD
system.
nmin dctos md
tuteescceEhhdxnntiirqtqauuocee_ticowwianrassacssptiirmmoiciplleeaadrrruft1lroeu.ottrhhoeeTochootennaeenoeppaxrrteetevrvaiiocofuturissoollnymy
RESULTS AND DISCUSSION
RESULTS AND DISCUSSION
ooh mono uization detector; an~l
nls can be monitored
Gpuplslaeiisdcmtmaatoc((99h)e)e,;xrthhrooaewcwxettevrveapercre,t,rafnttlhthueeowr88ao00so%%ctraehhnieeoaxxacaatenendee//f2wr20oi0%tm%h riTTnhheeleviiennloosrrggfaannniipcclafMsluumooarriddoeef aarnantdds oosrruggcaanrniiicfdflluuoos-t-
tdhieetrh,ylmeothreer peoxltarracstaont lwatvoseernespurlarce,aed mwoirthe
different intervals arc shown in Table 1. In- rine levels in plasma of rats sacrificed at
different intervals arc shown in Table I. In-
:uunndd CChhooww ((RRaallssttoonn
_ionoguustws,,iM tMh o.0)asainnn. dgdlWewA) oaLrtEaeTlr
Lg obain sufficient quantities for the GC/ ececroothamm)eprplc,leaeastteeems,eeoxxritettrrapawccoattlsiiaoornnnseocooleffvsesmmnaetret,yattsbobo1l0oeinttipsteoeusos.rl.e IIpannlmasssoeemvrv.ae-
eral eases, it was necessary to pool plasma
oorrggaanniicc fflluuoorriiddee lected urinary
lleevveellss iinn samples
pwpellarasesmmaasigaannniddfiicinnanssteel-y-
lheicgtheedr iunritnhaeryexpsaemripmleenstawlearneimsaiglsnilhicaanntliyn
2H-perfuorodecandl ing with a single oral
t, 211- periluorodecanol
tMoPoDbtaainnalyssuifsf.icient quantities for the GC/
the controls. This observation suggested a higher in the experimental animals than in
the controls. This observation suggested a
aVift.b.oaiubGGlnieiledirtrtmmyytoaaffnoncoyory)n)bbtiiawwooiaatsnsrsaanlasnesussn---t
nMiPO`gODnnaeeammnSia0lil-llylimisllliiistte.eprrooolffyprrraatotpppylliaaessnmmaatuwwbaeass (ppDiiuFpePettottneedtd i3n3t5o4)a f5o0l-lmowledpoblyyprompiy|eonfewattuebre a(nDduP1 omnit
dodfeetffhllueuoosrriibnnoaatteiioonpnesrsttueeopproiindnettchhaeenabblii,oottrSraeanlnesscffotoerrmdmasattaiimoo-nn polf sthoefabtoheverapterpflluaosrmoadewcearneolt.hSeenlecchtoesdensamfo-r
sanaondalssthcan found to contain less
:taaoate and less than
r3e2a8g4e)ntforllaowdeedhbyydro5chmlloroifcwacaitde.r Tanhde Icomn-l
furthercharacterizaotfitohne organofiuoro ples of the rat plasma were then chosen for further characterization of the organofluoro
Jin 100 ml of pure Ifen.. EEiigghhtt ggrraammssoofftthhee
] in 100 ml of pure
MINUTE Was TESUS
(Baker, anhydrous grade) and centrifuged yrteeeaanigts;enwwteergrereadeeexxtthrraayccdttreeoddchwwloiitrtihhc
7acimdi. Tohfe ectohner-
7 ml of ether
(3Bmaikner,(1a1n,h0y0d0ro)uwsitghratdrea)nsafenrd ocfetnhtreifeutgheedr
ccoommTphpoeouuennfdfdessctpporrfeesmseenent.tt. hylaitsihoownn in Fig. 2whTehre etffheectsaomfemseathymlapt(iolRnaelis s1h7,ow24nhinpoFsitg-.
: rtli~turc was
mogheonmoegietnyi.zer homogenizer
before resus-
before
pe3phniraaescien62u(ul1sslii9,nn0)gg0t0aaog4p)poowl1lyyi0eethttmhhyytrllpaeeonnnlseeyfaeddlrrrlooooppmfppeteerhrrece((enNNttahraliel.-cr 2ddbeoowfssoaharggeeeree))atnhwwdeaassgaafrrmeuurnne sdooaennmripttvhlaheetei(zGGRaCtaCit/o/M n1M7w,PPi2DDt4hhssdyypissaottzeseomtm--
,:mditohimmegmeemandleeeiidotaiyhta.otelel-lyycobbreenffoororele fcgfluoegnnceeettn6uut2bbr1eea9t(()eNNdtaaolulggnaeednne1ere0-33Nm11y1li9a9)pt.)o.TlSyTh0ahelelCoeemxtxotetrrraaabcccotetunwwttraaiss-| tmbmeehetfetohhearaenndeae,in.tdAAissoaafnatr!ereerssRuduulelottrriooivffeam-mticezeotatnhthtiyyoallniaantlwtioniingtoh,ancat,dtoimllaeepzaaeoss-t-t
:amatllaheue/ulklaaagtltceeoaddnhdot(o0l-(chg6oaivtr%nevooa8lni1:l pcmLooi]ln.ncTgTehhneetrmaeeitxxettdorrfaauccsntttiidhooeennrr,wwNaaa2nssdarrteaepp5hee0aaittCdeedd,,ttoitthmhaieibssovttuiiimtnmgee1 tnnheernTtethesseawwsdeeidrnreiegtlioooebbnpssaeelerrvavfleeudndoriiitnnnheethh-ecneooncncdhthaerrironoimimvnaaagtttoioczggoerrmdaampemox.--
twmtoioglcehfaakcc3ghhiarrnaadttnwwtihitltahht aav]o22l-- u5C5'osinmncglenoo6tffrmaeettltehhodeerfr..etTTahhbheeore,utttaoontt1daalmlaleextxahttnirrdraadccdttitivmwwiadaesesduttshnhientengno tttrrhaaeTcchtot reegllsiuuintntaiignlnlggeapaaltetoah11ko00li..n8(tCmmh.ieFina,nwoCwanHasds,esCsrhihHvooa,wwtOinnzHettd)oobebbxeye-
32swS+atiOOtihfofnahthiarstcetaee1in.arl2aet.tsss6s-.wWstEee1IreeSl2.10c(two01nocpoeTorn0ri.ttrmioaolntnNessdabbltyygoessanppblleoiitutttiitnunbg1gemttshhle(easstnaadmmupdpAlbilveeieabdbneeesdttdwwieeBnee)tn.on s~aotibopn oast d1,a2s, 6a,Tg1he2e, two41150,-m0l3N"algeneditauzboemse(tthuabnees Ain adnidthBy)l.
rtrpeheetetceetnnottritiioohgnenin-ttabiilmimoaeewlcrmmoaanhatsotcfclohhri(iCmnnaggst.F.itoTSSniiCnnHccoeef2CooennHneezOccaaalHcnno)heboxly. pfuenrcttitohnealbgiorotruapnsiftoormactiaornboxoyfliacnaaildcohthoel
ii
sith diethyl ed g0 h postdosagc. The
with diethyl ether and
ethAerboluatni0c.)3 wmasl addiadzeodmteothtabnee Ai.n AdBieptrhoy-l fnuenwctpioenaakls garpopuepariinntog aonclayrbaofxteyrlideearcviadt,izthae-
i
ether (toxic) was added to tube A. Appro- new peaks appearing only after dcrivatiza-
|
11225577..00000044
3WA0503478
3MA00509476
340
HAGEI~ ET AL.
tion with diazomethan were assumed to be
mT [a acids. Two possible metabolites of the al-
i Ton po mi A cohol were suggested, namely, CsF,~COOH
and C~FI~CH2COOFI- Perfluorononanoic
Fs RaRiciieedddeel(l-C-dd~eeFHH~TaaeCennOO((vvHiiaa)
twheasAmpeurricchaanseHdoefcrhosmt
the American Hoechst
i
Boe fo pi i rCoodrepc.a,ncSiocmearvciildle, (NCy. FJi.)y. C2HH,C,2OHO-HP)erflwuaos-
1
rodecanoic acid (CBF~CH2COOH) was
a kindly supplied by the American Hoechst
foo a men Corporation. These two reference acids were
rar i InoRaANEFLuoRIDE ANDORGANI FLUORINE.
i]
mfR rre A Rat plasma oncantration
a ww mm mm TTTLETTT Time.
post ~r~ag
R at
JS El e A nI o~ p ~ ow A No.
Organ ic fluorine
laor~a nic fluoride
FIG. 2. Eff~"t of esterifieatloa. (A) Rat 1"7 (~4 h ~-
Control
!
<50
<5
~ge) plasma extra~ n~lefifi~; (B) A after ~r-
A Ps od 33 2
<50
<5
3
<50
<5
4
80
25
5
140
35
6
140
40
BMD I o
350
40
II
ll0
30
12
250
30
7
410
80
8
660
70
9
470
35
WeBoBBL3 12
13
360
20
" - I4
250
30
15
430
30
Whom a 24
I 6
890
6~
[I 3 17
960
20
Ig
600
30
" pom 10 19
500
!0
POR 20
280
21
590
BOR 0 99%6
n22
2 320
<s
TOE 7 23
320
5
24
250
5
EPOBE 1 144
25
250
<5
26
3~
27
250
3 mg WW 5 3 20 days
29
60
30
130
31
90
"11 u4Mm ==00..001199 ppppm..
oSwrEEEERTENE ifi~tlon; (C) 1H, IH,2H,2H-~ot~aol
(a) IH, IH,~,2H-~uo~ (C~F,,CH~HtOH~ (x) ~r~ta~ (C~F~sC~); (y) 2H,2H-~r-
uu stor somehan derivation analyzed after diazomethane derivatization
separately and also were used to "'spike" rat plasma isolates for retention-time matching. Figure 3 illustrates the chromatograms ob-
members tained. The new peak appearing at 7.5 min mehmmimelim is the methyl ester of pcrflaorononanoic acid
aanndd tthhee ppeeaakk aatt 88..99 rmaiinn iiss tthhee mmeetthhyyll ~esstt~err
mmabombEe of 2H,2/-/-p~rfluorodecanoic acid. These
dau, therefor,indicatethatperfioronon- data, therefore, indicate that perfluoronon-
a er ne pe anoic acid was not. present as a metabolite
ui thepeak at 9min matches the re while the peak at 8.9 rain matches the re-
pemmaiaemanit tention time of methyl 2H,2H-perfiaorowe ddoeccaanncoaattee..
A German patent (13) indicated that
Amends methyl ester of 2H~2H-perfluorodccanoic men acid is readily (as least chemically) conmepemimens vetted to the corresponding unsaturate,
C,F~CF--CHCOOCHa via deflporination.
Chocicolw sem afIaltolssrwooebabwseeassaapsemmceeutytalaabbtoenlodilitttteehoaofatfhctttchhhoeeiesraadlulicscnnoosghhaioottuoll artazanhntdedeeatmthbhieeogdrrvheee-t-
fore was synthesized according to the above
`ppaatteenntt aanndd sshhoowwnn bbyy fAluuoorriinnee/N/MNMRR ttoo be.
11225577..00000055
3MA00509477
.
T _
rT
AIH 3HLPERFLUORODECANOL BIOTRANSFORNATION
1
I H,I H,2H,2H-PERFLUORODECANOL BIOTRANSFORMATION
341
paprrdiinncctiihppeaarllellyyforbbeyy lvvooolwlaeatritlilibittyly.i. nTTghheeth66a.n88-mtraihienn rppeeetasekk:
wee"nnnaccdsee thsmsaeaamrmtepepflholeeeredoolffotwmhmeeeertthrhbye!otlielnppinteeigrroffnltuuhooatrrnioomnntehoonenoaafrnneoofataethtreee-
ii
y
amINImnnneeMccdttoohhRrryypmplloodareeraatasctttttheaeeeedrd,dc,oooffnGGtafpphaiiceeinrrnrefmesloerusverdviotloirelltoclnehectt,e,itaoapnFnFnrolloeaaiisct..)iem.aanccceFFiiedldluuoo(o(offPrrPiCinCptneehRRer/e,-"],
i
dfNfleuuM cooarrRnooococicdtctaaatannacooiiicdcconnaaf~iuhrimddeedaaannttddhpe2l2HapHs,r,em22saHHen-e-xpcpteeerrraoflclfutu.ooprreoor---
3{
dmeec"OtaaOpnbphoohalieauiugsamcaaindnodfdinpSSieitnnrhggfeeeorrrrao((to11c44pi))laahhsnmaaovviaeecessaxttcuutidrddaiieceidtdn. ttfhheee-
i
mmm{aaeanltloeaeabtorreaalittsssims aannnooddtf pccoeoorrnnficcluelluourddroeemoddecttttsahhbnaalottlizcppeeeadrrc.fillduoIorinrnooootfchec.e--
tGpGaenririofuffaoitttrehaaaaisnncddtnaoLLntooonnftugger,t((h11e5v5ra))ssmtstltuueydtdayydboioofflffizraaeemmdnm.mtooInnlneiivutuehmlmes
p({raaebubrfoolmuuuttoorf1o1m00o00e--t1afaoonllvoddaa))ltfeooe,ffmeavoolrargegstaalnnryiiaccedwfhilfeuufreooerrreiinnreeetpoiilnrnetvettedhh.lese
serum of male vs female rats were reported.
SATS ahspea
T M=T ND nie n r t 3 piete f roneeewuedee(2ce 4%hFpcoo0rmpio5E nu0gn0d)sr0e(Ao )cRaptre:+ hhaannec ddeerriivvaattiizzaattiioonn used to "spike" at arter than 90% in purity. This wnsaturate used to "spike" rat on-time matching. Sasso one rom we ariger ion-time matching. hromatograms ob- Tuoodecunas acid seron the packed co. :hromatograms obpearing 3 7.5 min um, Figure8 illustrates thechromatograms ,pearing at 7.5 min Huorononanoi acid Obtained fo dervalized at plasma cxzact quorononanoic acid is the methyl ester before and after spiking with this unsata- is the methyl ester oie acid. These rated reference, As show, the unsaturte ~oic acid. These that perfiuoronon- utes slighty ahead of methyl dihydroper. that perflu0rononnt 2's metabolite uorodecanoae. In related work. the capi. mt as a metabolite i matches the re. arycolumn (described cari)provided the tin matches the re2H,1H perfuoro. expected greater esoution and indicated 5 2H,2H-perfluoro) indicated tht the CRoampoonfentthe wrheoesrencreeteontnisotnr(aitmee (mFait.ch9e.d Fperfluorodecanaic indicated that the
~'-cpheermfliucoarloldye)cacnooni-c chemically) con-
nding. unsaturate, ut paadp erivastive thereof ~nding unsaturate, via deuorination "The first clingfluorine containing om via defluorination. unsauratemight ound at 6.8 Tin appeared to be an cer ~s unsaturate might alcohol nd there- Since it required diazomethane dervaiza. : alcohol and thereo"dingrtothe above ion 1 rer tO late, The column ~rding to the above {orine/NMR 5 be uilzed in Hi case separates components torin/NMR to be
FIG 3. Rat plasmsextractsbefore 0d afer the sd
FaG ]. Rat plasma extracts before and after the dttion of two known reference compounds. (A) Rats and 17. pooled (6 h and 24 h ~td~ag, ~s~tively); (B) A spik~ with ~uorono~noi acid (C~F,?C~H and 2H.2H-~r~uor~a~oic acid (CtF,~CH~C~H (b) P~rfluorononanoat (CtF~COO-); (~)
anonte (CFLCOO), (y) 3.2 perfetadesannte tan~te (C~F~sC~-g (y) 2H,2H-~uor~can~t (CFACH,CO0"Y (3) unsentifed metab (C,F,~CH~C~-k (z) unidentified meta~lite.
greater than 90% in purity. This unsaturate was not well resolved from the 2H,2H.perfluorodccanoic acid ester on the packed column. Figure 4 illustrates the ehromatograms obtained for derivatized rat plasma extract before and after spiking with this unsaturated reference. As shown, the unsaturate elates slightly ahead of methyl dihydroperfluorodecanoate. In related work, the capillary column (described earlier) provided the expected greater resolution and indicated a component whose retention time matched
Thus, the peak luting at 10.0 min on the that of the reference unsaturate (Fig. 5).
NegTihues,dtChoelpuemank(Feilga.ti3n)g iantot10t.0heraUinnSaolnurathlee
'~cked' column (Fig. 3)is not the unsaturate but perhaps a derivative thereof. The first elating fluorine-containing compound at 6.8 min appeared to be an ester since it required diazomethane derivatization to render it GC volatile. The column utilized in this case separates components
Ts i
i
I LJ i
[71 , ,
Fie 4 TTheTdTenifwuTtienToTf he TmDate FIG. 4. =l-he identification of the un~atura~ (GFoCr=CVHeCkOeDs to afte (C,F+~CF=CHCO0) i~ addition to 2H,21-l-pcrtioo-
mone (CEH ruplsmaexes Loe moresseal ono Storie. rodccanoate (CtF,TCH:COO-) in rat plasma extracts.
1"his tepre~nts $ scparat experiment where six rats were ~i~cn a si~8] d~s of lH, IH2H,2H-pcrfl~orode-
Cas coe 4 be dst ot canol and sacrificed 6 h later as described in the exper. merscsion oe aefm he i rswp imcntal s~:ction; the plasma from ih six rats was pooled. (A) Rtpss ngs8) A td wi (A) Rat plasma, 6 h posldosag,; (B) A sp4ktd with the Sen (GFICEZCHCO0 (0) 2Hydpur unsatnrate (C,F,~CF~--CHCOO-). {w) 2-Hydroptrtreorddeecnnts ((CSF,ECFL=CCHPE0E0C") 0) ea: flnoro-2-decen~te (C~F~CF=CHCOO-); (x) perflnoH(C)mOeOeSe ~octanoat (C,F~sCOO-); (y) 2H,2H-pcrfluorodcc.ate (GF ACHLCO0" (0) soir mab noat (CtFtTCH:COO-); (z) unidentiiicd metabolit.
11225577..00000066
MA00S09478
3MA00509478
PS
342
ii --
iii
v
i|
{
ar
agen ETAL HAGEN ET AL.
| )|
eaSaesbbxetoorllmmivcocolddleieeecnrcriuuivtlvlaiaaatsrrtiivvmvmeeoieeriststakppbaoohsblsistioebo!al(e(Cni~nGFtJsteLhhsCs~atCtOCtsOthFhOe,Oessgmea)roaoalulbbl.p-hstheara"vnnTehdetthhieenmsestttthaaairrbstioiwnnlggiosriakmlcchhooahofsotlo.Mnueorlienss cCoFnt2agirnoiunpg apSastnnteudTdudrhidpupeededoerrrfmiilnunfseoohggtrarrrpoeebltaaoIottolinncsddmghece-atchah,nioialfln(nI0stfpacliucesiiocdkskrisniannohlhoewal-swcsynonnnttpohtthtaaetitbbnoeettinhee.ennge TBwprwhooehirorilficloleedtuaao-~ntrouoioo-ooafhlrntueeopTo)ccrtihiyoaslcmrmatebcrhtehboiataognabixahobynylrolliail(ccicrsncapgaalceaclllciinyydoiissfssicact1(baaf7aIbllu)l7leyae)r(ut(upiI1nned44ddr.e-foee1l1rru66ggeo)oo)Bipinneorxttuhihodeeractppiololasansts.mamTnaahoea((TtTheaaigbbhlsleeuing11og))regsa4annndtdihcefffolourromovmreaaritdtaiileoollnneveooe-flf
pcrfluorooctanoate suggest the overall
A
y
Fi 5 aC/dctondceacopraorftseokt F]o, 5. GC/electron-capturc detector o( the pooled pm plasma (6 h postdosage); see Fig. 4A for th z~me samBPD moet roms ig pl on MPD and note the simplified ehrornatogram using frat wp the MPD-spc~cific fluorine detector. (A) Rat plasma, 6
b posdenge, (B) A spied wih the sere h postdosage; (B) A spikd with the unsaturate
(Cher ooncoo). oy Sinyeoperares. (C,F,~CF=CHCOO-). (w} 2.Hydroperfluoro-2Sette CACPoOHCO0Y 0) perm dccenate (C~Fz~CF=CHCOO-); (x) pe~t~orcoctanEa Oy dnpub. oat (C~F,sCOO-); (y) 2H,2H-pcrfluorodccanoatc TEC0 No he went ami on (C,F,,CH~COO-). Note the unidentiiied fluorine coninmast o rnwe c) n: taining metabolit (z) is not apparent with the electronprima ied t:apt urc dtcctor. Furthermore, while the MPD rr.sponds tin corel cr to the total fluorine content of a compound per th emonc rt son Se eB pirica? formula, the electron-capture detector has difon mie To ain oop. la ferent scnsitiviti~x I'm different compounds. In SEeRr,GhEe Cdo0i0Ny, >8CChForCHCHHCOOOCHS this series, the sensitivity is C~F,~CF----CHCOOCH~
, || R
I
TThhee fflluuoorriinnec--ccoonnttaaiinniinngg_ bbiioottrraannssffoorrmmaa--
tion product of the coho] eluiog at 100 ee lion product of the alcohol eiuting at !0.0 i 0 yt eh ne O15 Fo 6socmi rs i, rain has not as yet been identified but it is specs a coma anon 8 BASSO speculated that it contains a carboxyl group sce azomethane readevrolse for oso( :Ko 0 (3h cm) since diatomthane renders it volatile for `GC. The unsaturate has been Hentfied (5) cm(Go FCHInCO 1 ()aidedova GC. The unsaturate has been identified (by GC retention dat) and an sddional met. hs GC retention data) and an additional met-
frees
FiG. 6. Rat plasma extracts at various times, postdoeag. (A) Rat 10 (2 h ~td~ ; (B) Rat 9 (6 b ~td~g); (C) Rat ~ (48 b ~8 )- (x) Perfluor~tanoate (C~F~sC~-); (y) 2H,2H-~uor~ ~a~ate (~Ft,CH:C~-~ (z) unMeatifiM mem~ lit .
11225577..00000077
MA00S0%479
3MA00509479
~sllee iinn tthhaatt tthhee ssmmaallll--
+ (CF,C005 0 me ess CFs group -" (C~F,~CO0-) oh-
one less CF~ group
aonconsinisng fluorine-containing acids has not been acids has not been friedied t is known that lhe peicaly prt: .pecifically pcrfluolystable (4-16) :a II y stable ( 14-16) ids (1) undergo acids (17) undergo aan frie eel ont buna et rganic fluoride level
~ and formation of
- 2gt the overall reN--
HAH FERTLUORODECANOL BOTRANSTORNATION 0 I H.I H.2H,2H.PERFLUORODECANOL BIOTR ANSFORM ATION
343
o actig on,
FReEFERENCES
CFCFLCHCH.OH -- 1 To 00) re ane 30,165 Se --
2 Tavs, D. R (1968) Narre (London) 220, 382 1. Tares, D. R. (t968) Nature (London! 21"/, 1050= 1051. 2, Tares, O. R. II96g) Nalure (Londonl 220,
CRCOr SHE 583. bik 3 Vem, . Sager Led Armes 3. Vnkat~swarh~, P, Siascr, L., and Armstrons,
ghnd Fir ET W. D. (1~71) Anal. Bittern. ~2, ~50-359.
Fie loses th cero cape Ver (7) Bk 8.9 Figure 5 illustrates the electron capture respons obtained for the esterified PASTS 5 Vso. (199 hen Med 14,368 response obtained for the esterified plasma hexotwrasctthoenstahempclapeiltlauryrceoluwmhnicsy3steSmimapnlde 6 B37 lJ 50 Hge, D.F.(198) t.Bicen. extract on the capillary column sygtem and
shows the complex mixture which is simpli-
ed by montoring any the Rain coment (FREES ne oofninedtthhbeeyGGmCCo/n/MMitPoPDrDi.n.gIIotniislsyaobbthrvieioofuulsusottrhhiaantteaacnnoniddteeeanaltl sim vould combine the setOfthe pa 7-14 Ane Chen. x. Women, system would combine the selectivity of the ocrowvihatesiomiprnoevded epouramtiopnmcassbdleise.s GuB ydT W.S (1970) creemre microwave-sustained helium plasma detec{on with the improved separtion opsbiliies % Ce Acub. Fries, Fpl 138 tor with the improved separation capabilities oF3 orley orem and 1 5 one Comune, PD. hin Une of of a capillary system and this is under evlopment at his te. Ran Roar. development at this time.
4. Venkateswarlu~ P. (1975) Anal Bi~hem. ~, 512521
5. Vcnkateswarlu, P. (1975) Bi~hem. Meal. 14, 368377.
6. Belist, J., and Hagen, D. F. (1978) Anal. Bighorn.
ay 87, 545-555.
7. Guy. w. S., Tares, D. R.. and grey. W. S. (1976) BL~hemislry Involving Ca~on-Ruorin ~nds, pp. 117-134, Amcr. Chem. ~., W~hiagtoa.
& Guy. W. S. (1972) Flaor~m~unds(s) of Human Plasma: Aaal~sls, P~vat=n~, Purificati~ and Charact=fizatioa, Ph.D. thesis, Onive~it~ of g~hcstcr, R~hester, N. Y.
MPD. plot of the ori channel 6-5, Dbl doenD.. (910d. Ben MPD plots of the fluorine chaaa~l re- 9.
sponsenareishlowneormvarioues rats T(Fge 6 So EwiiTe a am sponse are shown for various ra*s (Fig. 6).
Note that the 2H.2H-perfluorodecanoi acid ~_
ester is tthhe predommiinanntt coommppoonneenntt iinn tthehe,il.
Svportdoage 1a. The chomaiograms fn 13 Eis i C. Wess & P. Wir. Lod 2-h-postdosag~ tat. The chromatograms in 12.
Fiigon6 louf tthaetscthoenpr1o0gpeesritvueobuosvcratnmsotnor.. 12 geKttaes5.i(r15a7)rirse.(Re88, 3T530. Fig. 6 illuslrate the progressive bio~ransfor-
El ik 103 3 mDDiiaffrffieeorrneennoccfeetsshiienn attlhhceeohrroaaltteetoooffpbbeiriooftlturroaarnnossoffocortrammnaaottaiitooenn.
13.
1~4.
ofthe aechol between rats wer Obed. 13 Gin 1-0 nd LoeJ. 190)Ane It of the alcohol between rats were observed. IS.
Bcfislc~ L, and Hasca, D. F. (1980) dnal. i~l, 369-376.
Veakatcswarlu~ P. (i97~) Clin. Chlm. ~e~a 59,
LLjigg2gg7ce7Rn-,,28LL2M. M.. ((11995544))~Annaall.. CChheemm..2266,, ~4488--7~5500..
Clark, L C., W~selr, E. P, Miller. M. L.. and Kapian, 8. (1974) Microv~c. ~e$. 8, 320-340.
German Pa~cnt 27 g2 685.
Ophauigg, R- H.,RH, aaodnd SinSoggenr,, L (1(190)9g0) Prere~..
Exp. BioL Med. 163, 19-~3.
Gti~th, F. D., and ~ng, 2. E. (1980) ~mer. Ind.
on AS 4.755 Hyg. ~ssoc- Z ~1, 576-583.
ACKNOWLEDGMENTS 0 ss) ee 1 Tr SiDJ 0 S050 ACKNOWLEDGMENTS
16 UbcL F. A.~ ~ten~n, S. D., and Roach, D. E. (1980) ~r. Ind. Hyg ~ssoc. J. ~1, 584-589,
We ih1 haope smnof Vek 17. Sede (971) Cro i Com. Wa wish Io acknowledge the contributions of Vicki BeRx Not Ar Fk amd por Chey, eam 1d Bon Bannelle, Richard A. Newma~k, Robert A. Prokop, and Rn oer freomaetirewadutens Robert E. Ober.
1~. Saunders, B. C. (1972) ~n Car~n-Fluotin~ ~unds--Chcmistry, Bi~hemistry and Bio[ogical A~fivitics, pp. 13-15, Elsevier, Amsterdam.
at various time~, post-
oe ah ~OSag: (B) Rat 9 (6 h Cig ve ~ pos~dosag). (x) Prters (y) iran z) unidenlified t~etabo-
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