Document 4vOzmEOBv5wJGnxBdrn4xEbxQ

J. pESTEO JAN ROLE Cag even sng sows offeptrevion ant ioe AR 206~0M5T Distrimersonof Tovel Garbuns. n hale god Fond ats Fear Sinaia Iv dese of Felitbsc | RECEIVED Samsary 30, 1980 Feo ss Conducted at: 3m SRuikseireaiLraorrTyaTOwEoeXrfmTImEeoCTsnOotLaOG85Y10ed1 pring: October to Novenber, 1979 I. 5. 3. Gibson and 3. 0. Johnsen Report by: Reviewed by: oS e tfe eryrin Sne seg marte ents RaRreegerS.a DTrEosoecCa alsorisnrfAio co2887 ol a pra-- oACamvraenrroyn-ietaxotmevanatess,ivne1s6es.re7vxomdad/ikfbefe:etrweemenancleemai1ln3e.1examtnade/nktfge)amnalodefrafFtaOte-sLiodfA-Liieigxcrc.raetsiFioennmgalolefe tLvotadlose rats (sean iiSaemcreeevtesidne8to5ptxeerniveoiidaaiumlaryjionewiFiaatn"sdot5e.xt4hc%erevdtoietadeofvenicykas3rb0iynp3eezciednnaty2s4oPfhoosuttrhsedodhsoiesle.e; Nmaotalerthaedriaotaectivity 5a(< 0hG1ee5tedocostfee.dthienindLoitvviees)rsueaisnndootf1h.e1fr0amoiarnlgeaBnlFsaa.ttaeaaTthaets1e736dsdaeayxyssdpiPofsoftsetreddnoscoeesss wamiratelhecorsamntassrilsehtraedntle2v.e6ls iwIneah BporevdiayoustoSxhiacietryvatsitoundys.of differences in Toxivity amd Lisews concentrations Introauction Cpe som, ree1az Denotes position of cabon-14 CFFG+e14x3periismetnhtesahmamtonbieuemnsPallatmmoafdatpoerifnlvueosrtiignaatteedpecsasribsoixeylimceanascido.f iAncrseearsiiesng aDTbahsveoirsTpattfieoorno;fdoseeilloiimmmiionnfaattiitoohnnesoeffreoxFmpOe-prLlia4ms3emanf;trso.amndtAheexsbceorxdeytd.iiofnfeIwrnaafsnocrnemeahctaeissosnbaeorenyn FthoC-s1feerosvreda hdIonasttihenegsocafonScriaeftnsftoara(et1ni).coensAobfyseFcrCoi-me1ps4a3roifinng.exLptiehvreeirmreaonnttaesplahanasdsmSbaxeFeaAnfTsEPelroafnrneeptdoetaett)eodcisonrrvmaeolsntii1gaate dfCoierivniimnanaleetiot(noFCpi-rnEoxvnpiaeelrssindaaannttdafoenaagynheaefraestmoeau.ltee Ta(hnPedes_seBxxcFpeoen-rt1i4mo3ef-nt1t1oC7)tailFnattrceae:vrebnWoohnui-scihewxeepxrceerreitmieonnt,s V"fenrrioeannpalwiaarssemdadesv(ii3t)g.hnedanUrtiFonee-p1r4oa3vnd.id1e4fCedceaosrtaalviolndlostbioentaglsaexvCpeeedrrbifomoenrn1t4p.osa(sbPisCbo-lrEepxepiseorvnidmyeannotdfe5)l;imination mecabetises. sethoas Radiolabeled Fc-143-14c STThhueembescraprebc4o5i9nf)-i1c415acL0at.bi5ev1lity4isCoi/famtgt.htihseDetlcaaoirtlbosofnyO)fFOsc-palez4cbIioLfp'i,ceatao(cnRtiik(vesireteyI,saobtocvohepeemiscItanrlvueccntthuoarrreya).cter ization, and radiochemical purity have bash seported separately (41) the C-143-14C was found to be suitable for metabolism studies. 02888 oY BEST COPY AYvaim Ap3oLE Animas Fc-Bxperinent 6: dCSoiosxnidnimgta.ileonChedaertiboeosdiyndMwiveveiirgd?hutaslCbmreratanatgsle,dmetftoonambowla3ic01skmsC0oc1adg3e3s0andfors(emx2e4uaanlhloSyu1r7smasptp.urrieo,rhewteorreats v{esraeryalaltoiweerd afrceidnga.ccess to Purinel ground chow and water before and immed re-uporinent 1: dvvFoeeisrrvieoengacf.eolmnoadwlTieehtdeioCbnhfoearddornyletwsodeciciRganihsdvtsiesvri?tdoruCaaPDnlugreridmanteestf,laolmgtrmeo2enu3tn7awdebeotckolhsio2sr6om9ldac,n3a.dgea(swnnadetafenosrre2xb0u2e48aflo3lhryo.eurmsaaTnthudprerei,cseateto fomeciately after dosing. posing Bg3ia2vce0hn.r3aat%siwanagsclleveiissvohledudot,sieonLi(cgvohintaltyatianiailnnegsveti4hn.e)1t4izoBefgdFwFCCi--te13h-413di-ig1g.9t'h/y)2.T0heetnhied.ro,seTahyneadsatvh2ee.rn0aguel df2eo.0msaelceofsodxi(smFpaCol-esEsaxbple(erFiopn-leGanxstptei7r)cinvesanystrin1)g6e.7wa(smHao/1nk3oi.j.1ecmtgno/gk)g.fdoistettehvdeasawvietdrehelqiasvegrdgeodsgeauwgifetohr 1/2" mn1ei6e0xdilnnegl." bCylaTshisenv8edrotsviionnlggumbesytorlhiuatcnidoF.nlawskaT,shepcdrasezupbsaocrinend1g4bySocwoevnoitLesunhtmiengowfiFtCthh-e140d3.o9-%s1i0ncNgaCilsn,oceluatnoidon Vas determined by direct counting (ses ApPaTALY 1. sample collection AUctarcihnteheofantditnheefaocffeesmaslavecerrierfaitcceoel,lfeocrrtate1ed7 awdeatryesinaatnnedervsatflhosretie(zasecedhe woTifatbhltheedsime1atlhteyhlrosusegtshhor4f.)orfBo3l6rooddays. vicahbseen,dzkai"ualnnl'depdzloabnysmeatxhsveaansdgeuspicrneeanptdaiironengd; paroaonrmdtpatslpaylnedebnyi,mmceelnidvtierarit,feulgbyartatiirona,nm.sKfiedTrnhreeeyssr,faosanawdehrewepionrginized zCveeoarmrebuslctaoigloslnebcpyteadds..plitSTtohinenegmtoatthrearlobworneveamsaianncidbnegaciocnlaelrdeccatfsirsnogmanttdhheesmfaoapurireinomaoojfnorPSikbieoncn,eessthooiffshatnetared muscle, and subcutaneous and abdominal fat were collected: 2 Charles River Breeding Laboratories, Wilmington, Mass. 2 purina Lab Chow, Ralston Purina Company, St. Louis, Missouri. Sherwood Medical Industries, Inc. Deland, Florida 32720. # packaxd Instrument Co., Inc., 2200 Warrenville Road, Downers Grove, Illinois. 02889 BEST COPY AVAN ABLE rreecsce 0er mmeeeee rraereseere ppreaacseffrr ccoirtne mstmptipe reste fSetisinLoooSf ia Remade tSedoSBo Selb e de ere ore th Ty it Sh shen Sth eh SH ties Sh ben ile Shion Senter ent id A mE e emis of e sabes of rinE10 fSea se2sho. 1TTine 3 eres Be BT TA a rig LE eres Tre oe vs 88 Vesti est Seas eo, Title COR830 biyn driastecolaonrdateixotnenotfoflievexrcreitnioan90isdaiyn saugbraeceumteenttwoixtihcitsyexstduidfyfer(e2)nceasndsuinggested wciotnhcenatdrmaitniisotnraotfiounncohfangFeCd-14F3C-1i4n3foebedser(v1)e.d inTheliuvreirneafstaemrplaes90ardcaystsotrudeyd frozen for excretion. possible study of metabolites as related to sex difference in T(hPeC-tEoxtpaelrimceanrtbon7)-14andexcinretTiaobnlevi4aanfdeceFsiguirsesh1owfnorimnalTeablreats2 f(oFrC-fEexmpaelreinernatts6). On by tthhereeavderaaygse,posotnlydos1e-.2tSoifncethethedosmeajowraspoerxtciroenteodfbythifsemsalmeallratasmouinntfoefces bteoitnagl ecxacrrbeont-e1d4viwaasurcionlel,ectietdisdurliinkgelythethattimesomwehenof>9t0h%e of the dose was total carbon-14 0f-o0u.n5d dianysf,eceTsablies 2a).resMuallteofratcsont(aFmCi-nEaxtpieornimebyntur6)ineexc(reestpeedciall5y.4rpaetrcneunmtbeorf5, utrhienedoscearbvoina-1f4eceesxcrbeyti3ondatoystpootasltdofseec.al cIanrbmoanl-e14ratesx,cretthieonratisio1o5.f4:tot1.al iTnheTarbelsuelt5s. oMfeatnhe titsissuseuecoannacleynstersatioofnsmalaebovreats1 (FC-Experiggnt 6) are shown ug FC-143-1C equivalents/g were such as as follows: lung, red blliovoerd,ce8l.l0s;,plsaksinm,a, sp3l.e2;en,anbdonkeidnmeayr,row2,.3.fat,Otmhuesrcltei,ssuaensd birnamienanhadconccoencnetnrtartaitoinonosbserravnegdinginfsruobmcu0t.1anetoous0.8fatwg/(g0..28Thueg/rge) waass caodmipfafreedrcntcoe raabtdsomi(nFaCl-Exfpateri(f<en0t.127) uga/tg)1.7 The days same post FtCi-s1su4e3s-1y'eCredosaen.alyMzNeodcafrobronf-e1m4alweas edfefteeccttiavbelleyienlianmyinattiessuaell (F<C-01.4035 augn/dg/)o;r mtehutsa,boltihteesfemfarloem trhaet baopdpyearbsy 1t7o days. Tahte36pedracyesntpoosftdoFsCe-14p3r-e1g%gCntdoisnewhisoleliosrtgeadnsiniTnabmlaele6.ratsOnl(yFCl-iEvxepreri(m2e.8n%t) 6) and plasma (1.1%) appear to contain a significant portion of the dose. G02891 6 References 1. MBaerlcihsle31,J: 197F8C.-143, Rat Toxicity Study. Request A67821 (emo to J.E. Long) 2. N(iRneepotryt)DayNoRvaemtbSeurba6,cut1e978T.oxicity Study on FC-143. IRDC Number 137-089 3. Johnson JD: Absorption of FC-143-1%C in Rats After a Single Oral Dose (Report) becemver 4, 1979. 4. B(eRherporFtE), JDoehcnesmobnerJD2:8, S1y9n79t.hesis and Characterization of Fc-143-tic 5. Johnson JD: Extent and Total Carbon-14 in Rats Route After of Excretion and a Single IV Dose ToifssFuCe-05D-i1g1gCrib(uRteipoornt)of December 28, 1979. 6. Johnson JD: Extent and Routo of Excretion and Tissuo Dispribution of TSoetpatlenbCearrbo20n,-14197i9n. Rats After a Single IV Dose of FC-807-1'C (Report) 7. FAletdmearnatiPLo,n oDfitAtmmeerricDSa:n SoBcloioedtieosndfOortheErxpeBroidmyenFtlauildsB.ioloBgeyt,hes1d9a79,, Mapry5.land, C2892 2 List of Tables and Figures Table 1: Table 2: Table 3: Table 4: Table 5: Table 6: Figure 1: Appendix Table 1: Appendix Table 2: ATapbpleendi3:x Excretion of Total Carbon-14 in Urine in Female Rats F(oF-C1-E4x3p-g1r%ime(nMtean7) DoAsfet,er 1a6.7Simngg/lkeg)I.ntrNaBven5o3u1s02 DPose15.of E(xFcCr-eEtxipognyiomefntTot7)alAfCtaerrbona-1S4ingilneFeIcnetsraviennoFuesmalDeoseRaotsf rc-143-T% (Mean Dose, 16.7 my/kg). NB 53102 p 14. E(xFcCr-eEtxipognriomfentTo6t)alAfCtaerrbona-1S4ingilne UrIinnteraivnenoMuasle DoRsaets of rc143-T% (ean Dose, 13.1 mg/kg). NB 53102, p 8. E(xFcCr-eEtxipognrionefntTot6)alAfCtaerrbona-1S4ingilneFeIcnetsraviennoMuasleDoRsaetsof Fe-143-TC (Mean Dose, 13.1 ma/kg). NB 53102, p 5,6. T(iFsCs-uEexpDgiysitmrenitbut6)ionAfotferTotaalSiCnagrlbeonI-n1t4raivnenoMuasleDoRsaetsof re-143-"% (mean Dose, 13.1 mg/kg). NB 53102, p 10. aPtexc3e6ntDayosf ADfosteerPraesSeinngtleinIMnatlreaveRnaotusTisDsouseesof(FFCC--Ex1p4o3r-j'pCont 6) (Mean Dose, 13.1 mg/kg). NB 53102, p 11. Mean Cumulative Excretion of Total Carbon-14 in Urine oafftFeremaleSinagnldeMaIlnetraRvaetnsouasndDoinseFsecoefs FoCf-M1a4l3-gRCats (Mean Dose, NB 53102, p 15,66.,78,mg/akngd, 14F.emale Rats; 13.1 mg/kg, Male Rats). DNeBte5r1m80i7n,atpion32.of Carbon-14 Content of Dosing Solution SRpeickoevderwyitohf TFoCt-a1l43C-gtpCb.on-1N4B f53r1o0m2Bplan6k,7.Biological Samples OCxoimdpaatriiosnonVeorfusCarDbiorne-c1t4CoAunnatliynsgisinofAqUuraisnoelS.ampNlBes525b8y4, p 29. CO2893 Table 3 Single IntirnaEvxFeconnroseuitseionDRoastoesf oT(foFtCFa-OlE-x1Cp4ae5zr-bs1op9ngC-n.1td(7rienanAfUtrDoeisrnee,?a 16.7 mak) SueFeoratiyieeao)n 00.5 0.51 12 23 sa 0s ss or 1s 510 wi wae was 67 rom T rat umbere re Ses sear 55.76 lols 5.32 94.36 1 5.66 sas ses 1a ess ree 7812.3 ose 1s 0.50 09 079 oso. om oa 006 om 00s oo 007 ous 02a ous 0.05 0az 0.07 010 0.09% 0.03 0.04 008 0.07 0.064 0.03 0.2 os 0.04 0.08 0.08 0.052 0.02 oon os EE 005 0.02 0.00 0.03% 0.02 00a 001 0.09 0.08 2 om oor owz 008 0.03 _2 oo 0.03 002 ose ous 2 om 2 002 001 03 os 00s _ 009 oo 2 eo oe _ 00s oo 060 105.7 100.3 108.8 95.5 103.0% 5. 2 Data are expressed as percent of dose excreted during collection period. acioactive content too lov to measure (< 20 dpa/al). 02894 --- Table 2 Excretion of Total Carbon-14 in Feces? in IntraveFneomuasleDoRsaetsof(FFCC--E1x4p3e-r1jeCnt(M7e)anAfDotseer, a1S6.i7ngmlge/kg) leFcotrieosn (days) 0-0.5 0.5.1 12 23 TomAL ee SIEeee e m-- 1 2 3 4 s Mean + 5.0. 0.59 Ln 0.75 0.06 3.08 1241.6 0.35 0.51 0.20 0.44 0.06 0.31 40.18 2 0.05 2 0.12 0.08 0.05 2 2 0.05 0.02 0.54 1.67 0.95 0.62 3.28 1.5412 2 2 Data are expressed as percent of dose excreted during collection period. "radioactive content too low to measure (< 20 dpa/ml). COR895 SR Excretion of Total Carbon-14 a in Urine 2 in Male Ces ase emits me oawims ar eemeweiss 2? Data are expressed as percent of dose excreted during collection period. COR896 ries Doren ener Excretion of Total Carbon-14 inret tne in Feces? in Male Dose of FC-143-"'C (Mean Dose, 13.1 mg/kg) 2 as ater eueection 1 2 3 4 5 6 Mean 18-22 =: 0.24 0.55 0.27 0.16 0.51 0.29 22-26 _k 0.08 0.35 0.22 0.23 0.29 0.20 26-30 2 _2 023 02 _2 02 on 30-34 _ 2 oo 0.21 2 oz 0.11 4-36 2 _ oo 0.09 =: 0.08 0.04 ome Ter on wr wr wr ew aime 2 Data are expressed as percent of dose excreted during collection period. 2 Radioactive content too low to measure (< 20 dpa/l00 mg). 02897 Taste 5 Dia(sruoe-EDxGipEsatrPriimOebLnu4tt3i-6o1]n9A?sotf(earTaontaalbSionsCgealre.b1o3n.T1-r1t4msaeivsnean)oMuasleDoRnasts TT we ------ee e R-- i. Liver Plasma Kine Lang ROMS skin spleen Bone barrow SuscsTtaancous mscte Brain mamFiatnal 299 576 laos 105 107 Las as ast 187 00 396 303 029 0.0 12 Lz 02 om 1m 1.06 0.08 043 0.69 06 0.01 0.4 0.07 0.23 0.48 0.43 0.68 0.50 0.05 001 oa om 0.06 0.09 ous 0.36 om 023 om 013 026 ow ieee 5.80 eds 256 are der 258 082 117 7.97140 asain 2s nas oomsos 0.86 0.85 0.774ous 0.28 oe 0.030.28 0.27 0.5 0.28 _ 0.+30.319 0.30.36 003 ous 015 028 0.0 0.8 0.s 0.818 0.204 0.08 0.110.08 _% oa6 zou: e------res 2 Total carbon-14 concentration is expressed as ug equivalents of FC-143-1ic/g. b Malfunction of oxidizer sample vas lost. Total carbon-14 concentration too lov to quantitate (0.05 ya/g). 02898 ETS Table 6 Pe(rFcCe-nEtxpoofriDnoasnet P6)resaetnt3ginDayMsalAeftReart TaisSsiunegsle Intravenous Dose of FC-143-1C (ean Dose, 13.1 mg/kg) --_--_--m Tissue 5 TT seRat Number6 wmmise _--_-- Liver? Plas? 136 191 469 3.45 2.08 3.08 0.39 0.50 Les 151 0.90 175 RedcerB1lsotg 0.08 0.06 0.41 0.29 0.25 0.26 2.754 1.26 1124 0.60 0.233 0.3 Kidney? 0.13 0.05 0.24 0.20 om 0.8 0.15 + 0.07 Lang? 0.01 0.02 0.05 0.05 0.02 0.06 0.04 +0.21 Spicer? 0.02 0.003 0.008 0.007 0.004 0.008 0.005 + 0.003 Br-- raien?---- 0.00-- 3 e0.-- 0e 04 t -- 0.005--0.0-- 04 0-- .004 -- 0.00-- 8 -- 0.005-- + 0.0-- 02 -- Data expressed as percent of dose present in whole organ. 2 DPlaatsamaarevoleusmteima=te3s1.3ofmlp/ekrgcebnotdyofwediogshetpr(e7s).ent in plasma. Dcealtlas.areReesdtbilmoatoedsceolflpevorlcuemnet o=f26d.o3semlp/rkegsebnotdyinweriegdhbtlo(o7d). COR899 ae Figure 1 Meaonf FCeummaulleatiavned MEaxlceretRiaotns of Total Carbon-14 in Urine and in feces of Male Rats after Single IV Doses of FC-143-2C (Mean Dose, 16.7 mg/kg, Female Rats; 13.1 mg/kg, Male Rats) 1004 0? 00-00-06--80--0--0--0--O urine r1e0m3.i1e+Ra5t.s4, ne5 7 2 gee & ' MUarlieneFats, nm6 83.0 3.9 3 2 o 0 4 8 12 16Days pos2t0bose 2 Feces Male Rats, n=6 5.4% 1.0 28 0900 3% i. sepenai 3 Setemmination of Gasbon-34 Content of Sosing Solution JTSseauatsmaretprlpekrndiidwoairnt15hgoetnoncehad1loSosieFibnenraMigartnoivegfadnsmoorFiS1aotFcdsir,vso7a3ipreitsnpEh.geeiytaitbFussoCneertad-srty1s4edweir34rrrm-ceeacrptdraloiopysooitninrSgnsetapos.JoeoclrouenumtinesotmaniesnnnsfwgsaasSeeorxy rBEFofoeeNnFtCCnEea-es1a4a3o-ai"er"CtsharolCrlraeneacdonyhoaAdnefesgtpieernImdTciooinrnnesdaTtSiha,enbilmnetaghlLe3.e3".u3Cm0TeiLto/eg2sr.c0hdooOrmfEsl FwSEaeasmtiicnoe atrlpceusilEeastmiendche.ayceh PE -- ? sBquusrotguiss nfometcoibtesta Ssuhbtiibvle sseevlevmemnitm-escciionneittiia"nt for specific activity = 0.507 uCi/mg (4). 902901 "16 Appendix Table 1 Carbon-14 Content of Dosing Solution S ITCliA/hLeoemr amVEL/e 1.0 wm 1.0393 1.0804 1.0849 1.035 1.0598 1.0328 1.0627 1.0655 1.0709 1.0847 1.0473 1.0348 Overall average = 1.050 uci/ml B 1.05G 0 yeA i/m 2.07 ng re1-4a3-s1-4Y,o/m = 4.14 mg/2.0 m1 dose C92302 i BEST COPY AVAIL ABLE amsenttn 2 rsacor very of Tora iCasbeon-1ts eomkBriian,IN GFCEoeorEdovopRnrrylTaggoIvoeoLrtyodmFoefaaymrtaotFaeSlpseorrcesap,ernb2 oen(-5114n0)forcolimnniecoattmCyrb,rueshtIeSay derbeerliceeo-dn8e 0sm7ol-t2eee4mccisiDearnnseaa.,h the BpsEi AEehlaaStoon dsocokcvehcovony or wots ccrbonte eFnreoeeureprrit eroptaoletitrceeiaistoodenncsihhoiconmeftesrsw.10ieatethkhlehs,staeoue5mohs0ereoenulfo,oethurrna"nhidascecpeea1tr0i0iroTomrakom)aeecnsrtomsfeoVereSdmsimelm1hyusitzeeMwotdotSsoRFarEscsy-t1Ssh4i3Iec-rzTcre,iya SE EaEmEm e e nFaeSE5pTeohpe oesmpelTlhneeetnssmTveeereteensspShmeTvRieerearcgnsbomaDnnssoSmeahheneedSeo)arremTsomrohnSsg oCEnoocnmeaE,eitnes oTS2hiFeckhIihTereoouurbTomeatarstssiontdnSgcc,aosuarmtaaitbneagse,cesfogmaipneadineianencdary,ooeftpseehrneseonneesmoeskFeeco"eodhvepebirSsoysriveanznrt.ereaecstroli.eSasemtrPaolccneeeors"wbeYet, r BCeoaminpearreingnrBmeoraunattSoinnaefseecFesraeostnsheoolknrefyectavspeSAeemieeraporyAenrneeTo wRhey nBvEneehEereRa2tS2le, RmTe EeeemmaamnScsesetomR afaorcnmaeitrnnailtte(iyasoshntBoswe.ntfooiurnRrseicdtnL hoeaevtseeiBrrosmanT ics5nosa%ntiTvhoSoonetssae;;td oc3tF5hoi0ssr8moopmFneeeeacninodricsrbeeeycTeoonvooetfesrycodSriasul bSashesaeeieda.osoneh+t 1.an Th ra at en Hey Tene i 02903 "ne Appendix Tbe 2 Recovery of Total Carbon-14 Fron Blank Biological Samples Spiked With Fe-143-4 10 wm? 97.6% 100.3 98.5 98.8 emer of Ton Ea TT Fre Ba Fecal Homogenate Samples Spiked With FC-143-14c 50 ul 100 ul 97.8 98.3 55.3 56.8 95.1 96.5 96.1 97.2 Overall Average = 97.4 + 1.6 TTT econ or Tou GerTI Fra BT Liver Homogenate Samples Spiked With Fe-143-"4c 10 uid 99.3% & 50 ul 96.3 Overall Average = 97.3 + 1.8 100 ul 6.2 2 pnount of reference solution added, 2 oaDatta sararee experxepsressesdedaass %2 rerceocvoevryery ({420HEfRroRmR combustS ion von] Each entry is the mean of at least 4 combustion recovery determinations. ach entry is the mean of 3 combustion recovery determinations. 92904 em Appendix 3 Comparison of Carbon-14 Analysis of Urine Samples by Oxidation Versus Direct Counting in Aquasol rTheeporutrinaerecbaarsbeodn-1o4n edixrcercettiocnoundtaitangreinporAqtueadsoalnd.disHocwuesvseerd, inthetrheis iisn auricnoencesronthtahtatnoatn ailnlsolthueblreadmieotaacbtoilviitteyoriscocomupnlteexd.migThot iexnivsetstigate tchoimsparpeodssitboilciotnyc,entcroantcieontnradtaitaonobdattaainoebdtafirnoemddifrreocmtcocmobuunsttiinognowfertehe rseasreultusrinferomsamtphleesc.ompaTrheisodnata(oaxriediszheodw/ndiirnecTtabcloeunt3i.ng)Theisme0.a8n8.ratiThouso,f the diniretchtesecouunrtiinengsaimnplAeqsu.asol is a valid method to assay total carbon-1 02905 Appendix Table 3 CboympaOrxiisdoantioonf VCearrsbuosn-1DkireAcntalyCsoiusntionfgUriinnAequSaasmpolles L--T SNeaammvTbpeelTrerTT SiDreGcotormcE orugtming GIoGxieoiE/dsi)zEe:SdT WEaceounting w 2 38.825 34.64 0.89 18.57 16.77 0.50 3 15.68 14.01 0.89 & 26.02 : 22.94 0.88 5 29.93 26.03 0.87 6 28.98 2k.63 0.85 Mean 0.88 22 Dato are expressed as ug Fe-143-11%4C equi"valents/al. Data are expressed as ug Fe-143-1% equivalents/g. Each entry is the mean of 3 deterninations. se 02906