Document 377rdyJLy6ggMNpLeJgdQnw1J

CER en sees IR 226-0006 Free RECEVED Extent and Route of Excretionang acDteirstsriSbuitniaoin oInftrTaovtaelnoCuasrbon-] rFEIE,| uN 50 12 = aM Deceaber 2, 199% 1oxicOL8 Conducted at: During: Conducted by: Report. by: S5R8ui.kbespridaLiuaa,broyMrioanttonreoisneost,a Tne. 35101 2 une to Gotaber, 197 5. 3. Gibson and 3. b. sonnsen enioDr boioda)pdansenthPsracmarYotiba/i2o3e0 Reviewed by: R{aDmO aige kDree gEfolcaboSiaiorns Y lg0 000037 . RV Summary 2 By 89 days after a single iv dose of FC-95-'%C (mean dose, 4.2 mg/kg) six male rats excreted a mean of 30.23 of the total carbon-1k via urine. Mean oc2uf0.m6ut;loatatplilvaescmaarf,becoan2l.-21;hexcekrxiepdtrneieyos,nsedw1a.s1a3s 1y2Tg.u6n3gF.,G-91A5.t-1$;149Cspsldeqaeyunsi,,val0me-e5na;nts/atgnidswseubreoen:ecomnacirevrneetrnr.,ation 0m.u5s."cle,Lowfeart,coanndceneyter.atioNnosra(d<i0o.a5c)tiwveirtey m(eas0u.0r5e)d wiansaddreetneacltse,d sikninb,raitne.stes, Trheespeccatribvoenl-y1.4 in liver and plasma represents 25 and 3 percent of the dose, Introduction #C5--5500,,"K* F * Denotes position of carbon-14 FC-95 is the potassium salt of a perfluorinated sulfonic acid. A series odtfefhresoiengxrnppaeltroaeisfnmoaeft,nhteesslaenidmhieansxeapxetcbrireioeemntneinooptnflsa.dnFanCte-aTd9h5iwtseofrreFoimCnn-vete0chs5eet-1sihgbgaoadrtyyeI.npttoorsaFsvCfei-onb9ro5lmuesaabmesebxoaaprnsepsirtsiiomoffenon,tfi.noocffr(fhemieaiscsniiaentngiton Experinent 3) which was designed to provide data on thor route and extent of total carbon-14 excretion was paired with an FC-95-14C oraldosing oeaptnlxhdapesernreailemixenepniletinrmaiiwtnnhieaiotncnithosfnwr,aoosnnanpdtdleheasseimpxgaocn.sresedit(bi2tlo)oenprbdIaointvoaitadrdwedaiinltsdlifaootnarb,meaotnutishoeetndsoteaotlfFoC-cFi9Can5-rt8be0aor7bnps-ro1o(r4s3p)atbainstogoonr,Fgpu0ti9id5oe.n Methods Radiolabeled Fc-95-14c The carbon-14 label is at the position a to the sulfur2fgm (see above structure). The specific activity of this lot of fos 'C (Riker Isotope sdIeuntiveteranmbtiloneraytfiNoorunm,bmeertanad4b4o2lr)iasdmiios csht0eu.md4ii5ce9asl;uCipd/uemrtgia.tiylsTdheoetfertFmhCie-n9a5st-yi'no9tnCheswhiaassv,e fbsoepuenendcifrtioecpobreaccetdi:vit(y1) Animals Dosing Six male Charles River? CD rats, eight weeks old, were conditioned to individual metal metabolism cages for 24 hours prior to dosing. The body waceciegshsts toranPguerdinfaroGmro2u6n2d toCho3w03angd, mean 283 g. water before The and rats were allowed after dosing. free 2 Charles River Sreeding Laboratories, Wilmington, Kass. . Esiancghlerativwadsosweel(gvhiead,taialnesvetihne)tizoefdFwCi-t3h5-1d4lCe.chy)Theethdeors,e awnads 2t.h0enmigiovefnaa 0.9% NaCl solution containing 1.21 mg FC-35-14/2.0 ml. The average dose was 4.2 mg/kg. The dose was delivered with a 3.0 ccdisposable plastic syringe (Monoject) fitted with a 26 gauge 1/2" needle. The 2 Purina Lab Chow, Ralston Purina Company, St. Louis, Missouri. Sherwood Medical Industries, Inc., Deland, Florida 32720. 000038 [on . 3 cdseohnsatikrniignfgusgofilonrugt.oinoen-Thhweaalsfsupprheoerupnraarteaatdntmboydwaeasrdadtirenegmos%vpeede2d0a0nidmngausofemdecFhfCao-nr3i5cd-aol'sCinsghtaokseo0rl.,u9t%iaonNnda.Cl, Tchoeuntcianrgbon(-s1e4e Acpopnetenndtixof1).the dosing solution was determined by direct Sample Collection owUfirtihntehediaenstdihxyflreacteestshewfreo;rre8b9lcooolddalyeswc.atsedAdtraatw8n9indftareyorsmvalptsohset(dsedesoesceeT,anbdlitenhseg r| atasndwe2)refaornesetachhetized aorta and immediately. ctleirnvaetnrrs,iffeurbgrraaetidin,otno.teastThehesep,arraiadntsriezwneaedlrset,ubseak.cidrniefPyilsca,esdmalbuwynagsse,xsparannegdpuaireneyaedstipowrnoo;rmeptaclnoydllbseypclteeend, 2rseawrholleegsorbgyanssp.littBionnge tared combustion padd. mtaherrobwonewasandobtcaoilnleedctifnrgonthtehemafroruorwmaonjorpiebcoensesofofa the Samples of skin, thigh muscles, subcutaneous and abdominal fat, and the total remaining carcass were collected. Sample Analysis for Carbon-14 agFneednceiszailniagnqduwoatmsianjdgoornaeorsgaiamnnpslWearwieonfrge tpbherleepnhadoremerodsgenbfayotraedcdaiirnnbtgoon-cn1io4nmebuasnptaairlotynssiscofonbweya2t.heormogH(eowmn/owi).zing cctooonmebounesatnidpoanratddcioonfngesbi1o.i0lnoggtircOiafpllitmchaaetteehroiomaonlga.enattToehp.e-lohCaoadmrioenggenwaabstaelsatnawkceeenrebytwoefimagirhixendgthetihneto mheoamsougreendateinbtoetwceoemnbusstaimopnlincgosn.es Ubyriwneei,ghrte.d samples of bone marrow, skin and fat were blWohoodleceelyless,, also weighed aanddrenpallass,msawndere In combustion croenmeosv.al samples Cianreordwears ttoakeanvoitdo weighed directly, wleoisgshofthweesieghstampblyesdrypirnogm.ptlyHom(o1g-e2namtiensu,test)isasufeter and weighed samples of piasma, red blood cells, acbnladarnbkounr-ih1no4emgwfeernroaentecbsioomlb(oufgseitcceeasdl, wis1taihmvperla,esPamuwcsakcsalrgdd,etMoeadrnedmlinsep3dl0e6ebnyO)xcidoainmzdbeursb,tlianngkRecsuorivatcearbyleo.f pmcilodaldsllmeeac,tisopaninsdkewdeenrdweitohfsamdtpihlleeudetxiopbneesrfiomroeefntfFarCle-e9z5si-an1mg4pClaenddosestwienrg(esseeocolAuupnttpieeodnnddiaitxret2c)ht.elyb;eUgriinnening, sttcoriinprtleiiflcrlaiatgteeiroa1nt.o0rvimlatlesamlpieaqnrduaottu1sr5emolfinAeaqtcuhehasdosaalrmkpwlaebsefwoeardrdeeedcp.oiupnettAiltnlegd.sdaimrAplellcestlrywaedriIeonmtecotoroilced aSnpaelcytsreosmetweerr.e done using a Packard Model 3385 Tri-Carb Liquid Scintillation msCtaoatunindctairnEdgx,teerfinfnaitlceirneSantlcayndsatfraodnridzaearatdcihownas)samaprdladeteidwoasmteotdhesotedel.remcitneTedod scaabmylpilbuersseatoeffrotmhtehetehexAtEeSgrrno(auAlputooctfohleslseeacmtpseladempslone(stphwurenerecehwitrtaephceoulanontwdedAEpSraolocrneagstsieowdsithabnydathtseheraelCeeOdCwis1tt7ha0n0dhaiCrgodhm.purtaeDtraitoasS)y,wsetraeenmd in wctaohsempua3tcMecroCmepnptlrroiagslrhaemdR.ewsietahrchtheDatBaiolPorgoicceaslsinAgutoLmaabtoiractoErxyt.ernaDlataStarneddaucrtdiioznatitoondpm 2 Packard Instrument Company, Inc., 2200 Warrenville Road, Downers Grove, IL. 000033 oo. a Results and Discussion aTnhde irnesuFlitgsureosf t1 heandfec2.al as percent of dose. The Tdaanabdtlaeusarrien1 aaernxydpraen2saslMeyidssetsastahreceumtusolthaaoltwnivceairnbpoeTrnac-be1lnhetseox1pfraednosdssee2d excreted versus time in Figures 1 and 2. As Illustrated in Figures | and 2t,otaelxcreextciroentioonf t(outrailneca+rbfoenc-es1)4 iiss osnlloyw. 43 Bpyer8c9endtayosfafttheerddoossei.ng,Radioactive content in feces excreted is thus was the too sum low to measure after 64 days; total carbon-14 of fecal excretion (0 to 64 days) andurinary etxoctarleticoanrbo(n0-1tho 8in9 udaryisn)e. (3T0h.e23)meatno trhaattio ionf fcecuemsula(t1i2v.e63)exwcarseti2o.n o+f0.2. TihininsgulreiinseivintdoocsotenhattorfasitFnC-tf8eoc0e7ts-h,1e1(Cr<.a0t,i(1o3)) oaftTci1u2sm4uldiaanytdsiivceaptoeesstxcrdteohtasteionFrCeop-foBr0tt7eo-td1a,%laftcieasrrnbooatn-14 FlCi-k9e5l-y1%extdeonsseivwealsy nboitoterxacnrseftoerdmedby teoitFhCe-r95-f1e4cCe.s orSinucreine50a-t6089perdcaeysnt poofst the dtohsoes,e tsieslseucetsed intiwshsiucehs wteortael ancaalrybzoend-1hformigcahrtbobne-1krhetacionnetde.nt to identify The results of the tissue analyses are shown, jn Table 3. Kean tissue ctfaoirlsblsoouwness-:14succlhoivnecarse,nmtur2sa0ct.l6ie;o,nsplskaaisbnmo,av,ebo2on.n2ee; mugaKrirdFonCwe-,y9,5-an11d7.1;sepqalnuedienvallhueanggn,tsc/o1gn1c+weenrterOatthaiesrons orfansguinbgcutfarnoemou0s.2 fatto 0(.06.2 uugg//g.g) aTnhdereabdwoamsinaaldifffatere(n<ce0.0iBnugc/aer)b.on-V1e4ryco1n1tteenrte -otcfoatratblootnac-la14rbcwoaanrs-b1o4nf-ow1ua4nsdrefitnoeunnbdtraiioinnn. wwhheoTnlheerleeiyveeirs,(0ab.o1sn6teruimgka/igrn)rgoawdn,idfafnendroensdcpeelteeecintnabatlfheteerptaottiatvlern dftoohrsesienFtgC-iw8si0st7uh-e1s4FcC-ad3fo5ts-ee1rd4CdorasitissngconwmoirptmaharleidFzCe-td8o07tth-oe',7plCia.vtetr(e3r)fngntToehfnetrmeeatraeenn:ticoanrlbiovfenor-u,n1d4 1c.f0oo;nrtent srspapltlieeoeesnn,/lair8ve.e9;rfiavrneadrt,iobo1nf.e0o;lmlaosrwprilonewge,n,FC2.-049..052-;14FCaonrdisFbCo8-n.9e95-1man4adrCrobdwoo,nseed0.m0ar2ra.trso,w/`S1tiihnevceemretahne oirs 2r.ahp,idlythibsiotdrataansfsourpmpeodrtstothFeC-9c5o.nclusion that FC-807 is not extensively sTheelecttoetadl whcoalrebono-r1g4anscoanntdentpslasemxapreasndsedredasblpoeordcenctellosf adroese lfiosrted aigneTaofblethe&. dosOenlyat found for kidney, l8i9verdayasndpopsltasmdaosec.ontaTihne alowsublsetvaenltsiaolf lung, testes, and spleen, are (in view preardcieonatc-tivity of the drueelatiinveplayrthitgohthcearblbooo1dnstciolnltenctonotfainpeldasmisn atnhdeseredorbglaonsodwhceenllsh)onogen- ized and analyzed. 000040 . -5- References (1) J(oRhenpsorotn),Jo,NovBeemhbrerFE:2, S1y57n9t.hesis and Characterization of Fc-95-14c (2) JDoohsenso(nReJpoo:rt) AbOscotorbpetrion26,of 19F7C9-.95-14C in Rats After a Single Oral (3) Johnson Jo: Extent o(fReTpootratl), CSaerpbtoenm-b1e4r and Route of i2n8,Rat1s979A.fter Excretion a Single and Tissue Distribution IV Dose of FC-807-14C (4) AM1al9rt7y1m,laann5dP.,L5,.FeDdietrtamteironDS:of ABmleoroidcaanndSoOctihsetrTeBsod FoFrluEixdpse.rimeBnettahlesd8ai,ology, 000041 List of Tables and Figures Table 1: Table 2: Table 3: Table 4: Figure 1: Figure 2: ATpapbelnedix1,: ATpapbelnedix2,: ATpapbelnedix3,: EIxnctrreatveinoonusofDoTsoetalofCaFrCb-o9n5--114Cin(MUerainneDosien,Ra4.t2s amfat/ekrg).a Single NB 52584 p. 17. Excretion of Total Carbon-14 in Feces in Rats NIBntr5a2v58e4noup.s D14o.se of FC-95-14C (Mean Dose, 4.2 after a mg/kg). Single 2TissisnugeleDisItntrriabvuetnioounsoDfosTeotoafl NB 52584 p. 20. CFaCr-b9o5n--1144C i(neaRnatsDosaet, 849.2Damyse/akfgt.)er NPIBenrtcr5e2a5nv8te4noopuf.sDDo2o1s.seePorfesFeCn-t95i-n1T4iCss(uesasnaDtos8e9,Da4y.s2 mafgt/ekrg).a Single ICVumuDlosaetiovfe EFxCc-r9e5t-i1o4nC NB 52584 p. la. o(feaTnotaDloseC,arb4o.2n-m1g4/kign) UMreianne aoffterRaateS.ingle ICuVmuDloasetiovfe NB 52584 p. EFxCc-r9e5t-i1o4nC 14, o(fMeTaontaDloseC,arb4o.2n-n1g4/kign) y FeMceeasn oafft6erRaatsS.ingle NDBete5r13m1i2napt.ion35.of Carbon-14 Content of Dosing Solution. SRaemcpolveesrySpofikeTdotwailtCharFbCo-n9-51-414cf.rom Blank Fecal Homogenate NB 52584 p. 16. OCxoimdpaatriiosnonVeofrsCuasrbDoinr-e1c4t NB 52584 p. 9. ACnoaulnytsiinsg oifn UArquianseolSa.mples by 000042 .: = <= fable 1 iEnxcRraettsioanftoefr aToStianlglCaerbIonnt-r1a4venionusUriDnoese of FC-95-14C (Mean Dose, 4.2 mg/kg) GPeorllloods(tdiaoyns]2 3 1 3iy p2 5 e agg Ee 00-.05.15 1-2 01..70002 oles 0.50 1.56 11 1.03 0.72 1.47 0.77 0.60 0.78 1.03 0.77 1.08 0.86 01..9247 2-3 43--45 1a 11.l1069 1.05 00..8807 114 10..0861 0.68 00..6680 0.91 00..9830 1n 00..9805 65--76 7-8 01..8067 00..7721 00..7657 00.l4s92 00..7764 00..7775 0.90 0.69 0.85 0.54 0.76 0.74 89--910 20-11 00..8862 0.60 0.57 00..3666 0.70 00..6759 0.60 00..5694 0.68 00..6438 0.67 00..7644 1112--1123 13-14 0o.s6e2 0.55 00..5523 0.53 00..5643 ols) 00..6690 00..6505 0.58 0.57 00..5597 0.55 1154--1165 16-27 00..5645 0.57 0.51 00..4438 0.46 00..5460 0.57 00..4455 0.55 00..4588 0.51 o0i.s46 1817--1198 19-21 00..5431 00..3490 00..2384 00..4325 00..4398 00..4464 0.93 0.81 0.79 0.77 0.84 0.92 2213--2235 25-27 00..9613 00..7559 00..6599 00..6767 00..7606 00..7878 0.76 0.67 0.64 0.66 0.68 0.64 27-29 2302--3326 0.73 1l08 0.66 oles 1.06 1.05 0.73 016196 0.68 01..8291 0.66 0.82 00..8664 114 0.66 3460--4403 43-47 00..5997 01..5088 0o.s9s7 01..0802 01..7091 00..9813 0.59 0.78 1.00 0.94 0.96 1.25 47-50 5540--5574 0.70 00..5623 0.52 00..7576 0.66 00..8622 0.70 0.83 0.69 0.75 0.63 0.58 0.79 00..6918 57-61 61-69 69-78 0.56 1.38 0.82 1.33 0.74 1.41 0.89 1.64 0.81 1.66 0.94 1:59 151 1.77 1.49 1.60 16a 78-89 1.59 2.03 1.97 2.06 2.45 2L.3a TOTAL 31.6 28.6 30.2 28.4 30.6 1.8 jean 0.91 01.:7271 01..9033 0.83 00..776 00..7658 00..5698 0i.s5o8 00..5554 00..4581 00..3493 00..8748 0.66 0.68 00..8668 1.05 00..9795 0.92 0.68 00..6718 0.79 1.50 l2.e0a8 0.2 # Data are expressed as percent of dose excreted during collection period. 000043 . 5 Table 2 iEnxcRraettsioanftoefrToataSlinCgalreboInn-t1r4aveinnouFseces Dose of FC-95-14C (Mean Dose, 4.2 ma/kg) PeCorliloedction (days) 00.-50-.15 1-2 2-3 43--54 5-6 76--87 58--910 10-11 112--1123 13-12 14-15 1165--1176 17-18 1819--1291 21-23 2253--2257 27-29 2392--3326 36-50 50-64 a _-- T2 E 5 thm ee -------- 00..7014132 0.955 0.761 00..773664 0.636 00..556309 00..444718 0.524 00..331191 0.351 0.328 00..224961 0.228 00..132748 0.357 00..028888 0.266 00..257700 1.397 1.086 0.7-80 0.770 0.572 00..663004 0.595 00..442634 00..343060 0.407 00..227798 0.255 0.233 00..127746 0.130 0.0.220754 0.258 00..313796 0.140 00..316164 1.074 0.663 00..096199 0.865 0.726 0.599 00..365026 00..893121 00..354927 0.327 00..320410 0.280 0.265 00..127746 0.171 00..127905 0.280 00..219348 0.197 00..429200 1.562 0.957 00..090848 0.465 0.466 0.667 00..339957 0.434 00..330367 0.299 0.295 0.304 00..239693 0.309 00..215726 0.156 0.111 0.294 0.303 00..225054 0.181 0.260 0.646 1.768 1125 00..717778 0.682 00..665329 00..550328 0.522 00..431413 0.371 00..226949 00..320202 00..225427 0.190 00..111107 00..237265 00..228108 00..214399 0.587 1.352 0.452 0.8-77 1.032 00..761899 00..552798 0.635 00..440511 0.433 00..337724 00..227986 00..228735 0.164 00..117583 00..334001 00..232068 00..223870 0.499 2.028 0.12 TOTAL 14.0 1. 13.5 12.0 ns 13.6 bean 0.0.084492 0.795 00..665469 00..551707 0.588 00..442812 0.387 00..239760 00..321801 00..227726 0.187 00..112693 00..330121 00..226028 00..222032 0.526 1.530 0.833 12.6 # Data are expressed as percent of dose excreted during collectionperiod. 000044 EN . a. mes in Ray ce at 65 Dp aye four a p Sirle T-- acvevamous Dose of PC-95-14C (Mean Dose, 4.2 mg/kg) TT a rs m em e ea e e, Tissue? g/g vg/g 19/9 ug/g 9/g va/q g/g Liver va mae am mas wes mar ase Pxliadsnmeay tsapnlgeen CL2o.s 0% os2.17 os a02.37 100 1m 2.27 am 21.1005 110 aa2.05 10s oe oso os os ods ome ae2.21 srees sReodreslmeaorsorCells 00..413 Mrems oss 00.5a9 ow oosms o0.m1 oosms ous om om oosses om oase am Testes sesicn e 03 3 os 03 om os om on eal om om om oz ots om swostmeows 0.05 028 ods 021 ons ons oa Bre ole 03s 03s ous om ous ous qBuraanitnitaantdeab(d<om0i.n0a8lugf/agt) weirneabadlosmoinaaslsayfaetd, buatndletvooelloofw ctaorbdoent-e1c4t wiansbrtaoionlo(w< to 0.05 zotal casbon-14 concentration is expressed as yg equivalents of 7c-95-1/g. ug/g). 000045 Lo -t0- Table 4 atPe6r9cebnatysofafDtoesre aPrSeisnegnlteiInntTriasvsueensous Dose of FC-95-1%C (Mean Dose, 4.2 mg/kg) le ---- Liver 236 ma 5.35 2.08 2495 20.8 5.2 Plasma "2.81 RecdenBlnoeoSa 0.42 2.82 0.64 2.84 0.58 3.00 2.75 0.41 oa 2.64 0.37 2.81 0.47 Kidney? 0.27 0.22 0.24 0.30 0.27 0.30 0.27 Lung? 0.15 0.1 0.12 0.17 0.13 0.11 0.13 Testes Spleen 0.10 0.09 0.02 0.02 0.1 0.02 0.12 0.10 0.10 0.03 0.02 0.02 0.10 0.02 C-- bata is expressed as percent of dose present in whole organ. tPaltaasmaisvoelsutniemat=e3o1f.3pemrlc/ekngtboodfydwoesieghptres(ehnt).in plasma. DReadtabliosodestciemlalste=of26.p3ermcle/nktgobfoddyosweeipgrhetsen(t4 )i-n red blood cells. 000046 Cl Figure 1 CumslataicvteerBarcsseitnigolne of 1v DTootsaeloCfarFbeo-n9-51-4Mein Urine " tenHaaonseo,f 46.2Famrs3ng) 0 0211s fa : i fo gS25 s 2 9 = % = [ Tw * w Py - Figue 2 Cumslative atser Excretion a single of 1v TpootsaelofCasrbeo-n-9l5e-Mtn Feces eanHaaDnoseo,f 64.a2cms/c) 3 i: i, i iiS s asia 8g3 = 2o To = = % w ww Days ost ose ua -1- Appendix 1 Determination of Carbon-14 Content of Dosing Solution 5cJ0aulsiutlbrparatileoidrquomttioscdrvooespriienpgeptiotpfoertrstadetdsd,,ir1etchmtellFyoCf-i9nw5ta-ot1e%crCouadnnotdsinign15gvmislaollsou.ftiAoSqniuxawasso1l0snawlmepraleneddawdsidietxch2, ccsaoplrecrcueilcfatitcieodna.sctiwTvehireteydmaaotfdaeFCafr-oe9r5-sb1ha4ocCwkngraoilunrneAdapdpyaenndddeticexorumTniatnbielndegS,1e.ffthieTchieueCnidc/oy2se.a0nda,dmlmiunswiaissntgertehde each 1.21 mrgatofisFC2-.905-m1l9Co.f sTohliustioisn acomnetaanindionsge0o.f5543.2UCmLg/okfg.FC-95-14C which is 2 1/1 micropipettor, Lab Industries, Berkeley, California. 2 AfqourasFoCl-95-y1a4s dfuoruinndgtsopbeeciaficsuaictatbilveitysodlevteenrtm-isncaitnitoinlle(n1t). dsepteecrimfiincataicotnivihtays b=ee0n.45r9epourCti/endg.(1).Specific activity 000049 .. "a= Appendix Table1 Carbon-14 Content of Dosing Solution 4C1/2.0 al Ci1/2.0 al 0.5602 0.5624 - 0.5554 0.5532 0.5614 0.5290 0.5628 0.5390 0.5612 0.5382 0.5554 0.5534 a LL Overall average = 0.5526 00.-5455386 ui /ng'. 1.21 mg FC-i951-h"C/2.0 ml 000050 ety roe Appendix 2 BiRoelcoogviecraylofSaTmoptlaels CSpairkbeodn-w1ihthfroFmC-9B5l-a1n4kC Tshaemplgeosodharsecboeveenry roefporttoetda.l c(3a)r.bonS-i1n4ce frthoem ccaormbbounsteldabeF)C-8I0s7a-14tCo tihne bisoullofguircal amteottoeamxbpoielncittbeostthhaitnFCbg-io9oo5ld-o1gri4eccaaolnvdersyatmhopeflecsotmotpcaoalnnenbcteasrabtootnfa-i1FniCe-d8f.0r7o-m1F4oFCrC,-e95ai-ct1h4issetarneodaf/soornabIltes sFaCm-p9l5e-sT,4condboussitnegd,Solfuotuironrewpelriecataelsiqouofte1d0 wuilt,h5c0aluii,braatnedd 1m0i0cru1opiofpetdtiolrusted dasniodrleutc1it0ol0nyulainndwtorpeispcaeitlntiteqisul,oltaetediiotnhdeirrveiactlthslr.yee ioAnrttoftchoeourmbsuarsmetepiloitnciamteceosnuessoinfwgh1it0chheyl,aslar5m0eeaduly choomnotgaeinnaetdesb)l.ankThbeiolcoogmibcuasltiomnatecroinaels w(efreecald,rieldivaern,d mtuhsecnlep,elolretiszpeledenwith h5anaddc.nbeateshnheleassdosdlevdefnitdlsitreerccotlpllaype.ecrt.edOne"iBnleaatnchkhe fovifilatletsrhetpoa1p0ewrhuli,cphel5l0tehteusl,FCw-ea9rn5-ed1hc1o0m0buulsteFdc-95-14c esnpdikeodf epaeclhletssetweofrebirooluotgiinceally csaommpbluesst.ed aAtftetrhecobregriencntiinogn, fmoriddblaec,kgraondund amnedancoruenstulitnsg effrfoimcideinrceyc,t apedrdcietnitonraencdovecroymbuwsatsiocna.lcuTlhaetedmeabny croemcpoavreirnyg data days for for three total sets of fecal samples carbon-14 (FC-95-14c) that were are shown analyzed on in Appendix different Table 2. : Tthhee mmeeaann orfecofvoeurrydeitser9m8i.n0at+io1n.s5,3. thiSsincmeeaneacrheceonvterryy iisn bthaesedtaobnle36is d(entotermsihnoawtni)onwsa.s alRseocov9e82r.y ofThutso,talgoocdarbroenc-o1vheryfroofm stoptiakledcatribsosnu-e14homforgoemnates Fe-35-1% spiked biological material is shown. 000051 oe 10m Appendix Table 2 Recovery of Total Carbon=14 from Blank Fecal Homogenate Samples Spiked with FC-95-14c --- _ 10 p12 750Mul t100wul be 97.4~= 99.5 97.7 "100.6 97.0 98.1 . 97.9 95.4 98.1 98.6 97.3 98.0 Overall average = 98.0 + 1.53 (mean * 5.0.) 2 Amount of Fe-95-'c reference solution added. =b Data are expressed as % recovery pn from combustoiorn tion x 100) Each entry is the mean of 4 combustion recovery determinations. 000052 oe [TR Appendix 3 SamplesCboympaOrxiisdoantioonf VCearrsbuosn-1D4irAencatlyCsoiusntionfgUirnineAquasol aTrhee buarsiende ocnardbionr-e1c4t ceoxucnrteitnigonindaAtqauarseoplor.tedHoiwnevtehri,s that an insoluble metabolite or complex might exist trheeproertis a concern in the urine so that cntoohnitsceapnloltsrsaoitfbiiotlnhietdyar,taadicooobantccateiinnvteirdtaytiforinnomdtdaheitraeucrftirnocemocuionsmtbicunosgunttioefodn.twheerTeosamiceonmvuperasirtneiedgatteo irssaemsapullevtsas.lifdrTomhmeettdhhaoetdacotmaopraearsisssahyoonwntoistianl0A.9pc7pa.ernbdonTih-xu1s4T,abinldierteh3ce.tuTrchioneuenmtesiaanmngplrieanst.Aiqouaofsolthe 000053 Sh er Appendix Table 3 byCoOmxpiadraitsioonnovferCsaursboDni-r1e4ctAnaCloyusnitsinogfiUnrAinqeuaSsaemlpdles Se ample rs er Diree ce t Counting-- Oxta-- ized -- OxtatzR-- eadt/io ee r Namber Cug/-- an)e---- r (ugE/g)E imDierrectt SCoOunRtiEngS . 0.98 0.95 0.97 2 1.04 101 0.97 3 0.76 0.75 0.99 4 0.66 0.62 0.5 5 0.86 0.72 0.80 6 0.77 0.84 1.09 Hean 0.97 2 Data expressed as ug FG-95-"C equivalents/al. daca expressed as vg eess-Me aquivatente/s. 000054 . co 2-. Oistribution Lise M.T. Case 218-2 Fp S.F. Chang .218-2 We. rotor --- eaeaeaa g L.1. Harrison 218-2 - T.L. Kerley 218-1 J.D. LaZerte 236-1 Ra.L.J. tMealgisloln 21223-65 nt. ober ae 1. Pendergrass 202 AL.R.A. PRrooskeonpchr 203236-38 Fh. thet ae P. Venkateswarlu 236-3A TDeMcGh CeCnotmrnail caFitlieons - 218-2 Central Files 218-1 000055