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UUNIENWILI. I pIIhcli,,1 , haul-c~ m Ihc Lupnx. Scc Table 6 lim clas%i(iealinn ul' Ihe I' 1', cAp,,.w, lunc. 1:l1 I'.,dipJr,nu,i ul Ilic Irrynh ll:T = 2.1 wcckxl; ,,IdL,I,1.i „I Ihe I,uyn~ 1U I' - 18 :,nd 5b tvccAa, rrspcclivclyl: (,1) . I, ,,.upL,l,., nl II,i I:uyu% IPI' = 71 %cccka; /c,I/ p+ipill.,m.iluus L.,.,•I.,I ,., „I Ii,c I.,n'u. 11 1- S.1 ,,ud 72 wrrl.s, ir>prrlncly!; lti q/ ku:upL,l.ia /hypeipL,.i:,1 ul Ihc I.uynx Ilil tu, g- SS ~.,. 1., l.., h, 51 ; lur I. Gj; lur j:wd k, l.l; lur 1, lu, :~nd u, '1'1; lur u, 55; :mJ fur p u.l y. 12 rcccl.o; (1) early I11V:1)IVC C8ICIIWIIW (I.I ° 72 K'CC{:SJ. : t , -t •~ • '~ nlw~Y:a3 ~ ' , ' . •. r ' , ' .,: .. tnl i..• f~' t,r _ ~~~~' ~~., rrl~~~ ! ; =. . 4~Pk ;'1 ~• ' r

t)UN7ENWILL I-tt;ruc 1•1 clearly shows that (1) only a few animals are surviving after a s/rlrlcl.:ully long period of exposure; (2) all animals exposed to smoke for more :.''y~ tll.ul 11) luurulu exhibited changes in thc area of the larynx; (3) Ihe degree of,' ~,v~lity I,I file changes corresponds to the duration, concentration, and Ilctftlcrhly ul exOoYllrt:; and (4) llle smoking cycle is, therefore, of lltnlost tl„Ih„ rl, Illt1 ulJtcome of the exrerinlent. 1!'Irat rrr.rl• Irc ctmcluded from file results of ttlese experiments? I. L,r,rl; I,:I,u ex(lusure to high but wcll-toleratcd concentrations of cigarette sul,rl,c Il c, 1., „Irtiulal (loses) induced epithelial changes in the larynx which are cunsidclc,l I., Lc Inecancerous.• Results of our experiments give evidence that CalwNure (u NuuoLc, /nlder the conditions and metllods just described, is Irl(Illcing IIIIIIUIS 111 Ilre IJt Vrl\. !. Ihnwy Il,,,~ (rrcatlling in smoke-exposed animals, (hc fast-moving smoke stre:wl is sltnt•c•I J.rwn considerahly as it passes tlle narrow nasal orifice and culels file L•Ilgc u:ls•d cavity (Fig. 16). Particles are deposited by impact on file innicate tullliua systcln of tlle hamster and the smoke flow is slowed down consitlerably (I:IIr. I7). Since deposition takes place on :I large surface, there is ubviously uu liu»ilnllly lilr the particles to settle and to concentrate at definite parts uf any surl:r,t: .nca. It is not Iikely, therefore, tllat tlle am(lunt of smoke acrusuls re:rcung I.cr ,urfnte unil of file n:lsal area is high enough to intluce lulnun. The Ilieli r„lnwlury fretluency of the obligatory nose-breathing auiul:Js •I'iua1 JL%,ifi.rn,.n ..i rLe Iiiidings in the area of the larynx after Iong•tcnn exposure to s„toke, aI wdl .u Iil,.J ,. ...I.. ,.1 rhu eaperirocnt, will I)e re(lortell ClSewtlcre. 16 kuugh wndcl rN16. .. ...il antl oral cavilics uf file hrwslcr :rtr'ording lu lu.rnl..r,i..d utr.d Icrrr,.niul I..~.~~ ..L„ 6c.iJ rcl:,.•ua. LFI•LCIS(1F- CIGAHL-1 IL Sh1UKt INIIIU Al I(N) Ir// I u:. 17 (luss SCiti.nl 11uou1•Ir Il.:ad „/ h:w,a.A .L.- lu,; uJU,.d., luildn.ll curn.hlcls Ilre snn)ke sllc:lnl in less Illan Ic,ll a ac, ,.,..I I„ I:uerl 0r1;.lu uf ilupail, file Iarynx, I>Io,lucilil!, u t:rqlslJel~rl,IC .I,. • n„1 II ,: ;luul.c Iluw u1d leadinl; lu file JcIxylLluu „( IIIt; I+,ienlc%t :unuuul r.l I•.,I II, nL.,tCS uu a iln:rll :uea. IlcacIiuns ultservctl Itl I11t: I:uyllx in:ry lie czlrl:un.:,l 1,, Iliu I, .,rlc 1.1 acliuu. •I•lus liyluwlllclic:d cxldauaLlull is aulllwrlcd I.1 .I tulr:d:rlitrn eXplri- nlenls willl ''t('-I.il,elcJ CIl:,ncllc slu.rl,t .inJ II. I'. It:rrke, wt1ntlrlislictl ul>servILiuuS)A (u Conyp.unlg Ilic i.l.,lr„n ,I JcI).,slletl la('•Lilrcled pal lit:lci in tlreilnukc I)ass:ll•c (lnuullr r,i u.i.:d uaclle:l, :md lung), it iu111tI lie tlcluirtlSllal~rl Ilr.ll file :rlu„ntil ,.I Jcl,.,:,ur,I Ii:IIiICItY rlue5 Ilul t:urrespunrl witll file sull: cc :uta „l file Imull"d.u ~tael,uo In Ilie pasiage ( I'able 71. Tllc vnuunt ul p:nll,:ul:1lta Jcp,r,ilcJ lu 11..: 1., A:Ilitht::ullly n ctt:uetl, Inl nuolc Ilsul wuul,I Irt: .xl.ccl,:rl I n U,,iul.1,', :/,up.i,a :uul rlcluisllwll uf I,:uLlrlcN :rlc Culihi,lcl:d,l.: licic. Ilic .uu.,uiir .I I,.rilirl•,, ,Irlr.lsilctl in llic I:uyllx, Irer surl:)ce unil, ni:rlx, file urlcli;il)• .,1 Ili,; I,i.~„I..ill~,.l,,,•I ,J IinJiut;i nl Illis arc:r iwdr:lslanrlald~. WII:It alt: file pluipeils (-I Ilrr: ic;ult'. „1 I. I lus is plulral~l~ _Ilie /li;l uu ': I1-1 II,.: clt.. I I lutel sulrrLe on :rninclls r,)nltl lir ICSICJ uutlil L „r,li,-IL:J, :,l ,..I.Jlliulu :lurl Inu.•c(llucs; arl urtlrluvc.l luu,hl %).I••u I,u r.ui„I r i, i, .1 .i-Jir. li;l% Iliis slUtly I,,,,,il,l,: r

...•.,"....,_,. 7•A Il I-I: 7 I)ry,urtliull o/' 14C-l.abeleJ Smoke Parricles irl Parlicltlar Regions uj tlre Rerpira(ory l}ac•(• 4 '. ...u..,. h.lly t)r~an tirllmaeJ t'Jiuc/iv11 y11y neporilion ul paftKlc/ Proporhiunal are/ u( Ih6 t u 'fraculJcpmlliue i/1lclaliun In lli „~ n (rJ'4 (,~/ rc.p a ury pru1wr11unN Irul area S.S 37.4 p_L1- pal.le fu.,~... ,r 1 I Or.I t:avlly 1.6 10.9 m luld 0.1-0.3 XS6I-187 7.6 - IraceJ I 51.7 0.6 x62.3 10110 X I lur.l I1.1: 14.71 100 hlracllu LI,,I,J ,..d. I'1'. I+nh..aJeun; J.u repreunl mun values frum 10 .nnnab, cal.ulneJ (ruw aur(..c ,II,II ILul.,,u ),. 11.- 1...1. 1 I 1,. vluc uf 1-1./ ,,-,U.SB nanu:uncr ar erlunaleJ from quanlily of deposition in Ihe nonlnceJ otcl ?. 1Vu :ue :1111.: I,. 1.:st lvllule smoke of rnodified cibarelles, which previously r:ullid Ilc rxanllu,:J „uly as slurllcc cundrnsate ull skin ur suhculancuus lissuc. Only Ille iuvcstle;lu.n, .,I' whule slnuke un the respiratory tract gives us ;1 clear ;I1lYwl:r IU IIIC IC;d (1.Im 1,)'. ItEFERENCES I W. I)onlcnw111 :luJ 11 r.Ld.l , I IIICr 'I rJCI1eJl- Illlll ItrnnilllJl•cJrcllllllllc bci Coldllanulcrn 11.601 ItchanJlnng rull I.1.,.1.) Inlll.n.uuin. A7irl. IYur•llsrlrr.. 39 ( 1961 )•7'11. '. W. I)unlcuwdl .,u.l II : 1.•1,,, l',uL ln,rlue Jcs Itcal,lr.llwns-Iraclus nach 11¢bandlung vorl r:ulJh,uual.aul.ul,•,,.nuul.'l.. A•rcbr/urscA..6d (1'161) {IIS-J1?. I. U'. Uuu/cnlv/ll, 11. t L.lu, .,,.1 AI. L.Ibcl, I1Gcr .IIJ unlcraihicdhcllc I.unUcn-carrlnngcnc l1'u6wlg .Ie. Ihalh)I„Ir,.. .,,,lu bet Ilalns/cr uud Ita1/J. Z. A-rehsJirrsrd., 6•I (19h!) -1 •/'1 ll) 2, 1 1:• Uuul.nwill ,In.l 11 I{%(krimcnlcllc llnlcrsocllungcn zlnn 1'rublcm Jcr w}• uauunlculalchuut; lul Ic. ,...,uunara/ l. II. Illc lVul.unb vun'fal):Ilrauchkuudcrnal.n n..l Ylg.ucll~ru.nl.'I. .IIJ d.. 1./..~: Jca liul.lh luufcra. 'l.. l~re/ afura'rA..nS (IY6I)e! 68. ~ •~r• ~ i I I I a:cubcrg, t 1, cu1J Illt inclJtucc ol prilnary ucupl.urn ul Ilic Inng m r, .. .JLIU., lnulrsc..1'.vrr/,., I i_, I'1%1) 561 -56L. I n,ulcuwlll .In.l I/ 1S'1. ) 1,, f/,ri6c:,I and pulmqnaty allcr,lllulu fulluwiu); Ihc 0 L,L..L,II.,u ui .Ig,u;ll, au)•,I . _ Ihc guldcn harnsler. In, l.unV '%unuqrrs irr:lnimrlr, pp. i 1/ ~ o, I.. .lclru Ic.l.l I). . „,.1 l'~Jnrcr ltcx:nih, 11, ul' I'enlgla, I I:dy, 196e. ~ s, N. Ii,.W:rllvlll, ti. I1e.1.r.J, .,..1 1., 11,,dIC1, Iu11Al.llrullx•\(,crlruculC nlll (lt}Irtllcu• /.,Bdd/u,r.A., , r/ ~./, 1 ~137 •t-t7. II 11'. I,,.nlcu.vill, li. Itc..Atct,, .~,,.1 1 Slydl.r, IlCrJ11cI111116'sJ)II7JrJtllr Iilr I.abot:UOriunu- t,, ~ uc,c. h. tlr. /:rGuk%ura.A., •1 11'•. ', IS J'I. ~J •1. t. It~,I,tch, K. Ku,Let, II I 11•,rl,c, wnd 1V. Uunlenwill, llntersuchuugcn zur ~ IIC,In,uu.... y dcl aLl)Icu uuJ 'foxitilal vun ('11;.IrCllcnr•ul.al hk:i pav,tvcr ~; IJ, 1.,1„ I...... ; v.ul Vcl,u.l..n.l... , .,, n,ultrll.u),/rum;. ?/1'/n'1) 2 I7 !.11. br 1.1 1 I.I:IS U1* I:Il,nl(l I 11 :;t•1u1.1: II'JIIl11 ,111tIrJ 10. K. Itii.•Lcr, anJ \V.1)unlenwill,'I'icrcxpcriwenlcllc Irulenu.llungcu IJ..1 lic II•;1„/ln:• sung Jcr .almmig w:ihr.uU Jcr Inh:ll.lliun vun (ig:neUcnl:ul.ll. la:r„ (:d.,rl./,,,.,ir, 1 (196'/) •tll •1•!. II. G. Rccktch and \V. I)unlcnwill, FIfcrh uf cig:ucttc anwkc un,ham,m,. I\I-Inu.•ul•J sludica un akin Iclupcr,llorc. buJy wcir.lll, Ieul,ucylc :lud c1y11,t,,.y 1. l.rL J:irrirurr. llrul(ll, 21/ (19711) 7-I i. 12. 1V. 1luulcnwill, I1,•I', llalkt:, (1. I.aticat, and G. Rtckzrll, I)ic \VI/A)uq: v.m Ilcl.rpyl.u, Ligarcllcnrallchkundcn.)11 und passlvel lIcl.wchoug aul Jic Ilddun,; .Icl lu~../..l..uu). IlyJruxyluac.l:'rprrirnria, 24 (I96ti) 71•1 715, 13. It. AI. \VcL-b, 1'. Iti. Il,lrnwn, It, \V. Guwwi, I'. J. 1'uppcl;, M. I In,Icr, ..uJ A. II. ('unucy, Slirnulalury et(ccl ulc'ig,uclle slnohing .,u Ihc ,i 3,•1-bcutpyrcnc anJ Ihc N-Jcmclhyluliuu )l 3-Inr(llyl-I ulunu u.cIL) L.lul)n...tul , necu Ily cutyu,cs ill Iluluan pla/:cula. (7rnl. I'!lurrr,dru(. '171rrup., I1111•4, II Iul/ Illv. 14. I'. F:ulln, I. .\. Alllchell, cuwd 11. L. F,dl., '1'Lc rule ul In)l1u1cJ .d, .1,1.1 laclllla In IIIC I)JIIIUgC11Cal] UIICAI,II:Il.u)' l/.ICl i,NICCr. In, A'r.'/,a h.~l,lllrt'Nl..(,.,rl INI./ J7ulisfiR rnu/igrlrr 7irrll.rr4n, pp. I~YI 181, (7. W:Igucl (cd.). I. 'Jr,LIE, 5111116:111, 1')/,tS. 15. \1'. 1)unlculeill, II• Fllncuhurst, C. ttca.trh, II.-1'. I1:)rLe,:,tlJ I. rtl.,,ll;l. I~pclila~nl ll~ Ilulcnuchullgcn liber Aulu,,hmc, :1btr.,nspurl uuJ .11.L..1. ,.. ,..la r uc) G,Jlku- w,,» cralullc ml IlcrciLh Jcs I(t.plr.rlluiulr,)I;Ira. l.. l rrha/..r,, l. , I I/ I'h.t4/ -' 25 243. 16. O. 5,dliwli, F. (btia, anJ 1.. II. F:ull., A Incllwd (u/ tt,, .I,.: Ia1c1.1.J Iwl.),nun ol' I)rUI1C1111E~111.: l"JR:I/IUIIIJ. ~arfl't'r I(tU'., 28 ( I'I611 ) 101 - I-'.1. 17. K. AI. I IcrruLl auJ 1.. 1. I)unhau/, Indu.aiun ol' Lun ...nl p..pill,)ma of Ihe Iracllcub,unr•InLI mucusa ill Il.c Syliau II-,wtslc/ b)~ uil..,u.,,l..•J unrlll.,liuui u( bentululpylcuc.l. Nurl. Caplcrr(nsl., _'1i (IHn?) •Iri7 -1'll 18. I:. AI. IlcrrulJ aud I.. J. Ilnuh,)m, luductiuu ul Iwuul% u, 11,e SYli:.ll Il,m,>ICr willl IlclhylniUua:uuint (N-niuuau,Ilclhyl:nuiucl. ('rn,-;r l'rs I'11. 1/ // I 171. 17. III. I:oa.llucr, llrc J. Ilullu AnJ)claun I cclluc. I hC ,..u.. ..,1 I.u.g c1.:1n1. 1te'r. J(es7nra(. l)is<'ases, !113 ( I9611) S74 SYI). 20. F. I.. 1VyuQcr and I/. Ilunw.lnu, I'ul,,rrr„ nnJ Tubur.,. .1'furlir; in ii.ip.•rinrrnldl ('arrinu4.~lrsis. Atadrlulc 1'Ic.., Ncw Yull,, I'11.7. 21. IL Ilnn l,lcy nnJ It. Ihc1l.,/u.,nn, Yur I flll.,...dulue:nu Ilclapicl Jt.l',di,ILrau,Ila.A'unuuncrni.h,l/l.vr, -I'/ /l'/t,?) I'IN 1.v 2?. 11. (luu, I•~l)c11u1cnIrI1C Ill,ldl>nlllllllACrI ,111 (11.,11.1. ,ul I,J•M,.1 1i1;:IfYtll'nl.ul:ll- Lr,duu/ul;. l•ianAJlu-l.•I i. ISrNn,(., 'I 1 11'16 11 Ill t,. ?l. 1. I.:\,h, f.I. It. Ilc.l,,:w.l I I/. 11'r11.C u,, I uuluu..t Ih, .Lp.. .: .I,n..l„ly Ir,n:l anJ c•Ir1 hl,.l rl•1) u/ lilt,lrn /'a/ln,l1.4,', Sc... I\', 1•,,-•.- I! I I I I' I1. I'h, I f)IS(:USS1t7n1 T. Clur••kcr: I cnu vcly iulclcsitll iu Ilic ,II11• Irlll/.ll, luclahr)Ilc I:I,Ie.:Ii 111 Itil!,IIcIIC \IIJI)LC CXIIUsr)IC run ILlIs, II,IIU11.:1], ll1i,l ).d, i, ill ••:I11~11 6'IC:lICt ]IlJVivAl v:.n Jc1u1,I1sUaItJ ill rwc sIn:clts Illan ill ..,u IJ:Ite Ihc luugef lilc ul $ul)IC :n1i/1J:115 IU InC1:111Ullk: CUIIJIICI.:IJ,..: 1..1 II1,~I..IIU, II„1. .,I IJm:uliUC. Is 111(:(d :1 C.,Ilclalnmu I)cl\\'Ccl/ 111e :)IIIIII)' I.) ]IIlvlvti, I....n1 I,/,.I.II,I,IIC III:ICllvallull .)1 ,uculinc, 1,11 caaulplc, au.l Illc tlcl-l.:,: .I /d Il:lcllcubl.mchiul cpilllclla7 Ilucs an :Illuu:il 111.11 I...,liuc ul ili Inclab(lt.; IIl1,lCl:11Vd InCChallialrlN, Cxllil)i1 (1,IC.ild1 .u L.. .:Inlll,.ll:d :Ihnulln:JiliJ~ in II1~: .)il w,l p? I

.11r) DONTENWILL W. Dontenwill: Thcre is not unly a metabolic difference wilh respect to nicutinc: we also measured Ihe diflerence in hydruxylase activity anJ futurd Ihat suhcuurncuus treatntent wilh benzolnlpyrene is able to induce zuxazulamin- hydroxyl:ue (2-aniino-5•clllorubenzoxazolc hydroxylasel. Furlhcnnure, we fuunJ a rliffercnt arlaptive enzyme pruduction in rliffcrcnt :tnirnal species: yt cuiyrnc :rctivily in Irrmsters is an order higher, whereas file enzyme system rats is c:qrablc of higher inducibility. Crocker: 1Vas tltis dilTerence in enzyrue activity assrwi:rtetl wilh greatcr or Irss Jel;rc.:, .rl clritlrclial :dbuuuncility? Dontcnwill: 1Vell, I Ilrink one of file diffcrenl reactions in :miin;ds, or in htnnans, willr respect tu rlilferenl carcinubens, comes frurn llre diffcrenl enzyiuc aclivily. We fuund in Itaruslers, for cxainple, a very tlitierenl enzynic activity. flie ranrc tiI tlie dilicrcucc is very high in one colony. Y. Alarie: Ii:•owIJ like to ask butli you and I)r. Aucrbach, wlral do yuu scc iu file Itiunclri.d lyiupli nudes ul your ;uuinals exposed tu cigarette snruke? 1'uu have presen[rJ .1 hiI ul Inslulogical slides on utlier areas, and I Iliink I)r. Aucrbaclr Irrr.rurrJ .i few un tlie lympli nutle. What kintJ of specific change do you see Iheic" Dontenwill: I ilunk file shecific change is a brownish pibrnent in file lymph nude, t,r a piulilcr.1ti"m uf file sinus ehitlreliiun. 13row)tislt pibntent, :urd black pignrent, tliat is all I I cre are not more reactiuns. N. Nelson: I)iJ N ..u w.inl lu add lu that, t)scar? 0. Auerbach: 1Vc ~~ hruwn pignrenla/iun within llte lymph nodes. We also see Ial witliin Ilicnl. x. %•.ell as reticulum anrl lyrnphocylic hypcrplasia. I would s:ry Ihal hecausr u1 Uir,r cli:rngcs file lyntph nudcs irr Ihe siuuking dogs are alruut fuur to tive tuur, i. I:nge as thusa: uf file nunsnwking dogs. A. Wehner: Iluw Ju you keel) Ilie animals in these restraininhcages,:rt :uiy given srnukin6 peo.,J, :rnil huw inany tirnes a Jay can you safely do Ihis urtliuul impu:int; an uii,lu. stress? t7ontenwill: In uuo Ittuccrlure wc expose aninr:ds tu sinukc Ilucc Uiues a J:ry liu I1/ rniu t:.. I. Rcliore calcul:rtint, Ilie arrtuunl uf suruke inlr:dcd hy tlir aninrals, it is nccess:rI> i.r calculale llle respiratory rate as well as Ilie number ol iuipiraliuiu by tlie Ica .niiiuals at a given liute. In lianisters the rcslm•,t--iy rate is ahpruxiinately 100 inspirationsprr ntinule, ,u wlicii we expose tlieni i•, smoke Ilrrec lintes a day for 10 nrin caclt. Iliis would arnuunt lu 30(10 inhaLatimu tiI smoke/air mixture for eacli Itatnster. There is nu pussrhdity during thit tini: lor file animals to inhale stale snroke, because file siuukmg chanrber is filled vcry ullier secuntl with fresh smoke, so that llie li.uiutcrs ale exlwsrd iuntulu,wsl)' to Ireslt smokc tlurinb tire inlr:daliun periud. 11 is mrnnrt:nrl Itr Ilre srnut:in); cycles and lirucedures uf ullrer I EFFECTS OF CIGARETTE SMOKE INHALATION 411 smuked for 10 min. I don't know, however, huw long tite srnuke uf one rnff stays in (he srnuking charuber. In case it stays lin only 2 sec, eaclr h:unster will make appruxiniately 330 inlr:datiuns wllen srnukinb IU cigarettes a day. As we have seen in carlier experirncnls in which inlraLrliun niaclrines of utlter cunstruction were nsetl, auinrals are Iiable lu stul) brcalhing for 2 sec or nrore as suon as smoke euters the ch:unber, and then begin breathing nurnrally as soun ats file srrloke is replaced by fresh air. This means tlr;il :r slay period uf suluke in the i ch:nnber of' only 2 sec does uul necessarily inake Ilir :rnim;Js inlrale tlre ufferrctl sinukc. Un file ullrer h:uul, wlicn snwke slays ill IIw rlcinrlrcr fut I nrin befure llre next pu17 is rlrawn, slale and aged snruke is inliulrd by file :rninrals ne:rrly :dl (lie linre. M. Kuschner: 1Ve have becn plagued tiu a Imnt, tiinc I)y file inabilily lu pruduce pulnwnary changes with cig:ueltc prudurl;. I)r. Nelsun rtferred earlier in llre conference to II)e hazards uf puur experirucnl:d Jesigu, rn Ilre face uf very slruiit; cl>iderniulogic evidence. I firsl saw Dr. I)unlenwill's resulls earlier IIsi; yccn in Lusanne with a bruuh of people who were tlrere I',r a UIl'C Cuurnrillrc Mccting uu inhalaliun cancer. l.uuking at Iris changes in file larynx, I was cunvinccJ Iluat tliese were, to tlale, file most impressive ciranges pruduced in llie reslriratury clrrllrelium by exposure to cigarette smoke products. As a rnatter uf I:rct, I Ihuuglrt it wuuldn'1 take rnucli rnure to convince file lllat these changes 1t•erc aIready invasive carcinunla. I think 11)at I)r. Donlenwill Iras been very mouhst in his cl:riin as to lhe nature of these changes. All of us would feel a little h:rppiei, uf cuurse, if the clranges extendcd heyond the larynx and everuually rnct:ut:aizerl. Iluwevcr, I think we all feel tlrey would if the animals were kepl alive Ioug tnuuglr. I think these results dernunslr:de tlre facl Ilcll wlrat we have been sufferinb fruin, up to now, Iras1 bccn (I) :r dosage rlcficicncy in uur experimental lechniquts, and (2) a failurc to use whole siuul:e, a very Cunrplcx inatcrial, which perrnils llie suntnlaliun of file nunl6er u(efle'ls. Nelson: Befure we end /he rliscussion I helievc Iliat I)r. Ftust has several conunents lie wuuld like to rnake iibuut file (uAurs tu bc cunsirlererl in tobacco sniuke inhal:rliun studies. A. Furst: For file pasl 15 yc:us tlie ('~ruiicil fur 'ful)accu Rescarclr -- U.S.A., becausc uf its interesl in file prublcn) uf liuni:rn snruking and Irealtli, has bcen cuncerucd wilh file proper biu:us:ry ruulliuds fur lubaccu stnuke inlialatiun research. '1•Ire scienlilic stal7' recumnreuds tli:,l tlre fulluwirtg facturs be cunsiJered wlren usinb:ur aninral ruudel. First and foremost, IllealnngfnI dala can only be obtained if file whole smuke delivered to file variuus parts of' file respiratory tract of lhe anirnal is in file s:une physical anJ clrcuric:d slate as that which reaches similar :utatontical :nc:u uf, tfile liuru:ur rliuinl; nunual cig:ucllc srrtuking. Iu urJcr to :rccunqilislr tlris, it is ueccss:uy lu have a nlecllanical device -a

412 DONTENWILL device should be able ttr dcliver pulsetl amounts of sntoke in a quantitative and tcltruducible manner.'t'Ite machine should be so dcsigned and constructed Iltat it will be possible tu measure accurately the time between two successive pyffs, file tiine of file puff; file volume of the puff, the extent of the dilution with air, and file number uf puffs per cigarette. Care must be taken so that the temperature of tlte burning tip dues nul exceed tlcN reacbed when a human snwkes-a cibarelte, mtr should the cigarette be "smoked" beyond a minimum butt length. 'llte macltinc shuuld have a port to pcnuil sampling of lhc smoke slremn for ,Itcntic:d ur gas cltnmtalugralthic att:dysis, if dcsired. I'or fracltutlallrtg (llc whole ,inol.e :uul tit permil /lte bioasscry of llte gaseexts plt•ase, lhe snutking nctchinc ,It~~ul~l Itc tlesiguetl so 11et1 a CantbriQge filter c:ut he attachctl, l~ur cumparisuns hetwcen lahuralurics, it is desitabla that a refcrenco-typc cigarette be used, such as Iltc urne nuw being prutlut:ed at the Univcrsity ol' Kentucky. 'Ilic mmtrnal tcceivinb file strntkc should be placed so lltat only its lrreatlting altpatmus is iu Ilte nt,tinslrcant uf file smoke and no fartlter lltan lltc Qisl:utcc ul file ltuur,tu nuse tu the ntain brauching of Ilte airways in Itumwt tungs. The auiuctt tnrrl slwultl bc futly described as to age, genetie backgruund, tveigltt, nultifiun.d st;ttc, physical eondition, virus ce>tnponents, extent uC surgical lrautna, ,nill tlte degree of stress tu which it is subjected. Apprupriate numbers of hutlt sh:+uranuketl and tage•Itetd animals should serve as conlruls. llle cml Itomts suugltt include more than morphological alterations and file y,irscticc •,, d,cncc of ttunors. They also should include :qppropriate bio- il1ru1i;.1l iur.1,utcutcnls and their analysis. A1uflivariale analysis should Iheu he al>IrIicJ 1" tlw ,I.1t;t nhtained frunt the systematic uhscrvations ctf' tlte c:unlrotleJ tmu,nneIet~. 1. Liuvc fu file sntukinb tuacltine, the animal model, and file I+i.+tut;tcat ;wd lui.rltentical uteasurcntcnts. lly these means, il may bc possible to inletlncl sum. ..I tltc Itiulubital elfects resulling frunt Cxpusure uf animals tu cig:nette snwL.• P,ra exlreriulents, wltete llte sule ubjective was the attetnpt lu inQnce ltunut,, mnt hc c:uetitlly and cautiously intetpretetl in lit;ltl td tud:ry's kttuwledge.