Tobacco Documents Online

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Table L Dmly critical cigar~tLe con~umptlon Column, I 2 and i r¢~/reserlt the Ioweft aver ~g~, and highest cdfic~J vaJue~ obtRined from m~ong MI ¢~Jir ¢ ~ponding ~Iudles Ci~lret tes INod ]~i~a se mortality Studie~ (No ~ (l/ ~2) 13) Low AV¢l~e High Cancer of the oral cavity 3 7~ $.8 10 Cancer ~the pharynx I 23 25 ~3 Cancer of the ¢soph~us 2 ~5 73 10 Cancer of the pancrea~ 1 9 9 9 Cancer nflh¢ larynx 2 3~ 68 10 Lung ¢~ncer 10 0 ? ~7 10 ~r~¢r of the bladder and kldney 7 9 9.J 10 CoJ~nary artery diseasd 3 3~I 42 ~5 Coronary heart disease I ~ J.5 3~ A~]~[e aneurism [ 4-5 4,5 ~ All ~u~e~ for cufTent sJnoker ~ 4 ] 2 2 3~ proble[12, howevel is not in. ~ul[nountabJe, because consumer p~r- Cel~tiun ¢~11 be mad~ to change, For iu- stance, the ~t rellgth 0[ cigarctt e~ today is flearly h~[f of what it was 15 y~ars ago, w~ll n2odern ¢igareltes would have been corl~idered too weak (30)¸ Tller¢ may be lower limits 0 f acceptabilily, and lhe succes~ of ~ome new cigarette this bci,lg the maximum ntlmber of ciga- relle~ that the avelage individual ~,uutd smoke daily without appaE~nt]y increas ing hi~ expected risk of mortalhy !ignifi ¢all fly above lhat of a nonsmoker, within the ~talislical variation in each ~tudy Table I s~mmarizes the resuh~ of this ~nalysi~ The low value is the Io~st of bral?d~ containing "~ io ~ milllgt ires of all c rlt~cal values ob/aincd ~rom the ~lud tar and 02 to 0.8 milligram of I~icntine, its reviewed; the average and high criri indicates that these limits might be quite low. Future cummercial cigarettes can he e~peeted ~ ~:h~llelxlg~ ¢o~roer at ceptabilily and to ea]l for cautious mar keying policies. These new ciga[etles will utilize compensating flavors and fra grances (31), and it appears that safety requirements can be met, particularly if added fhwors are natural tobacco c0m pollents, and are little pyloliz~d or a[ toted during smoking. Low-Risk Cigarelles The feasibility nf )esn ha2ardou eiga rettes poses an obvious que~tlon: Are there limits of cigarette and smoke corn position Ihat may approach relative sale ty? [a pragmatic tera/~ these Limits cart be defined as Ihe smoke inhke doses at which the risk of disease in smokers [~ approximately the same as in non smokers. Various way5 of estimallnN these values al~ available in putieular, the dose response analysis of several epidemiological sHidies and the cxtrapo ]ation of blood concentrations at difi~ ¢nt rates of intake for certain smoke components, such as carbon monoxide To derive a desc-resportse relation ship, cpidemiologieal studies as~ociatin~ d~dly eigarel~e eon~mplion i~ males with increases ill lisk of mortalily from II spot{fie diseases and of morlalhv in general were analyzed (32-44) A critical value ~as estimated flora each study. ~214 eal values me defined imiltrly The ~maliest crilica[ value on record i~ 0.7 shon]d be merllioned t/l~t this low poinl is the result of only role study i32) oflhe Ion 5alv~y~d [~lr lung ~ncer, the ~)lhel rline suppoctin~, ~ low value clo~er to five ei~,a~lles pcr day MO~I of the ~tudies hi this analysis were b~sed on data collected dLIrln~ the [95(l'~; because lhe diseases considered have a long ]atenl period, [I is fair to conohlde that cigarette ¢onsurnptioll be fore 1960 conlributed to Ihe risk~, ob selwed, Table 2 lists the ~verage delivery of some slgnilqe~ml smoke eompoflenl~ for cigarettes m;mufacttlred bernie 1960 [see also (6~49)i. Conservative estimates of upper limils of d ail~' ~.r~oke it~take ,[~u/d entree,pond to the Io,,veit intake doses associated with incl~ased risk in ep~emiologica] TZLbIe 2 Average delilety of smoke coin I~onerRs of cigarettes in~l~Jt~tclured before component clg~elle "far tmg)* 43 Nicotine (mgl* 3.0 CO (mg)~ 23 N<)~ Ozgl.+ 270 14CN (t~gl$ 410 Acrolem 0zgl~ 130 *S~les-wel~hted avera~e~ (4~, 47) tSe~ t4~ 4~ ~See (49~ studies It cQil]d Ic alguel] hllwever tha~ each xmoke cum9 ment shuuld he judged only in Lhe eonlexl of the ~l~ocia t ed disease; ~r hl~lanc¢, lhcre is no clear evidence thai nicotine is i~]ated to lung carl*;¢l., bul a case could b~ made ll)r its role il~ Colorlary heart dise~lse At pl~en[, Ihe ~ounterarguroent is iIIofe appro~ri~lle because [he causative allrlbntes of indivldua[ !moke com- ponents are ~u~ciently blOmted to be of concern. Ihe possible involvement Of nicotine in the etiology of lung cancer ha~ sol been filled out; i~ fact, its irl- direct re~e has been sugge'4ed by a re cent study (50L Thus, a CUllSetvdllve ipproach sag gests using the cnlica] vahles that apply to ~dl causes of death in 5mukels. AI- lho0gh 'all caoses" may inchtde some lhlt are sol lob[tutti related, this c tJ[ll pro henslvc category wpte~ems Ihe effect of riga[nile consumption on mortality in general These cdtical vatues are libldd in Table 1, and the ~elated critical valnes of smoke cnmponenl~ are listed in Table 3. Blood concenlrati~'n '~f calhoxyh¢ moglobin [COHb) is not dileetiy propor tiona[ to CO d~livery per ¢iglrelte; it is inllt/enced by the smoking and respira be~v, d~.r~ami~~, of lhe ~adNidaal an~ b9 the number of inhaled puff~ that a clgi~ rette dellve~s Based nn slandard consid er ttions I~/ $2} Table 4 indicates how man! cigarettes a smoker could consu ale duil~ before re~ching crlt[cal COHb v,~l ucs, depending on Ihe CO delivery peru cigare{te If Ihe hr~ crillc d vllues of Ihe range appear difficull to atta[rt--a slllokcr could argue thgl they imounI lo a no~ ~moking prescription the upper values ale in the lange of cunenl cigarelte mar- ketlng and malqufaclurlng realities, al thot~gh lhey would necessitate modifica lion of the acceptability requltements of the smokel It wc~u[d be errc~ue~m~, Io iatcrpret these clitiua] values as indicators tlf sift smoking level~, since the e×perimental ~nd statistic ii uneertaintie~ of the stud ins surveyed tr¢ welt known, as in mo~t epidemiok, gical ~nrk of this kind Also, regardless ul" how snphistizated the sta- tistical methods might be, the dar~ should not be interpreted a~ indic iting'~'1~ safe le'~ e[~, and special ptovlslons v, ould still be necessary for high-risk groups such as cnal uranium ~nd asbe,,Ios workers bn err h( ~er hould c aisle, ]~,e • , s not be ~i~ allotted to dilule the implication of these dala, namely that a rapid shift in cig~ rettc consumption habits toward the pro po~,ed range of critical vdues waubi SCIENCE. VOI 194

make il reasonable to e~poct that lhe currenl epldemie proportions of stunk it/g related diseases could be reduced to nlinimal levels ]n slightly over a decade (2). This expectatlon is plausible because cunem technology can reduce the specific toxicity of smoke condensate well below the levels prevailing before 1960 (tt, 16, I8) All of this evidence is not new, as mum of the epidemiological studies repolted were completed I0 years ago h ~as disregarded, however, fo/ t~o reasons The critical values were tDaught to he too Io~ and beyond manufacturel s" capa bilities, and there was an ethical eonflicl with prevailing antismoking attitudes that have recenlly given ~ay 1¢~ a more pragmatic approach, The technology for producing ciga- rettes, lO to 20 of which per da'~ deliver smoke within the suggested range, has been developed and can be applied on it mass scale by the skilled cigarette manu facttlrer I'hus Ihe 5ingle atol~ iroporlaal and potcntialiy successful disease pre- vention oprmrlunit} in contempol al y so ciety can be set in mutio~ by responsible marketing decisions in the cigarette ilt- dtlsIry, by a major public e dug ltion drive leading smokers to new palterns of u¢- ceptance, and h~ the promulgation oP judicious legislative incentives Not the least ptonllse of low-hazard ¢~garetles is th~l a low delJv~gy of ~i¢O- tin¢ and smoke will reduce thep habh. forming features, and ~ill make il easler for smukels to quit altogether Since the~e approaches are feasible. delays are difficult to justif!*; the altcrn ~ tire is the ¢ontimlalJon of hund[eds of Ih~aamls of premavare death s ~lnd many more disabilities every year Sllmmar5 Antlsm(lking education c~ml~algns ~n olaf ~oclet}, have met with only paltia/ success: today 55 to 60 million Ameli cans smoke, and the habit is incleasing among leen leers and womc n 11 is impor rant to protect individuals who continue Io Sfttoke despite all warnings There is evidence that this can he ucet~mplished in at least two ways. . First, it may be possible to remove toxic smoke components alld tllus r~- dace sFecJ~ic hazard~. Second, the dos~ mspon~ evidence suggeMs lhat, if the total intake of ~,noke can be reduced, after an appropriate time a reduction in disease incidence should occur, fhe techaology to achieve these results has been developed and can be applied to the monutaclure o( coolmerclal t;igamt~es [7 DECEMII['R 197fl Tab}¢ 3 (.!a,*ica~ vaJues of daffy intake 19" se. letted ~moke total'orients ba~cd on d~ll:~ as~o elated whh all causes oi disease moria]ily for curret~t smoker~ For COl4b, crlti~l valucx are ~4~lessed ul reims of the perce~ti~¢ in creasl~ of COH b in ¢h¢ smoker s blood, as de scribed in (JTI For th~ lemalmllg com- ponents, the critical values liste0 in Table I for "all ~.ause~ for currchl smoker~" w~re mu[t i~]ied b~ dl~ con esl~I~ding average deliv edc~ of s m0k~ compon~nl~ li~t ed in Table 2 IO obtai~ critical v Mt]es in I~rms o~ s ruok¢ tom portents Cfili,~al values Smoke gompot~ent {1) (2) (3) Low ,*vvg Hig~ ~ar (me) 65 86 151 Nicn n (me) 4.5 6 0 10 5 COHb (increase. %) 2,6 32 4 8 NO,f~g) 40~ 540 945 HCN l~g) 492 820 1435 Acroleln l~gl 156 2,30 455 Thexe cigmettes will nol conlnlln to ira lllllollal I]avor pillle~nR, but {'otl,,unlcr peoge~tion can be made to chat~ge and cortlpcnsating flavors and I~agt ante,, can be added The feasibility of le~s hazardou eiga rett¢~ ndses lhe question of whethc] 1here are limits of cigarette and smoke ¢or0posltlon tflat may itpptoach refallve "~dety. I here limits can be defined as lhe smoke intake doses at ~hich the r[~k of disease Jn smokers apl~ro~lc})es ~J~l] ill nonsmokers Such values can he e~li maled by dose-response analysis ot ~ev eral epidemiological ~tudies and by ex- trapo[ttlon of Hood concentlations at different rale~ of inlake fol cerl,dn smoke components~ such as carbon mon- oxide• Critical values determined hy these methods should rmt be interpreted as indicators o5 safe smoking levels; they do imply, however, that a r'apid shift in cigarette consumption habits towdrd Ihe pt nlx~sed range of wdues will make pus sible a subslml[~d ledu¢tion in the cur rent epidemic propo/Titms of stlloking- related dlse lses Tabl* 4 Daily ¢,igarenc consumption needed to reach critical COHb [evt~ls, as a t unction of CO delivery per cigaretle It is asstl~¢d that the ~o:lMl:llpfitln ~f ¢ige~ettes i~ everdy spaced over a I 0-hour p¢~od; see 151)¸ CO delivery Daily clgareltc consumption g~e[ ~Low Average High cigarette Clltic~l critical critical (~gl va]ue value valu~ 2 J9 22 35 5 8 10 16 10 4 5 7 15 2 3 5 20 2 2 4 R~f~rell¢¢s *aid Not~ { [966L p~ i271 in E~i,o~m,~l,,; Faemr~ ~,~ Be ~raro,v DJae~e, FI~ K Dee Ed {Academic ~e~, Ne,~ York 1972); O rl~erba~h, ~ P Slom~ E~ C Hamrn~d~ I G~rfinkeL ,'~, En~l Mea~ ~65, 253 (196~/ A drawer* £ ommmee m the Su,x, er~ ~ Ge~,,~ ,~f file P.bfi( Hea,'r~ ~lerefce ~Go~e nlme~t Fllmin g Office, W~hmgt,an, DC [g,64); The tleu,'th Co~euuence~ ~d'SmoLi,~g--1~74 (Go~emment pnnfin t I~ce~ Washington. l) C , t97al; World H~a t Org~n,~auon~ ~1t0 gec,l~ Rep Ser~ ~%o 3 M A Schneiderman ~nd D • Lelm. f,,neer 30 1310 (19~2K E L~ "~'y nde r ~ L S Co,~ey, K Mabu~hi. J bead £a~re, l~1~ ~t, 391 [1973~; U~S~ Department of HeaRh. Educanon a~d We[[are Th~ Ad~,q [~e erTr,bmeu 1970 ~E'e~ ter for DK~a,e Control. nurca/l of H~a]th E~uea tiom Attanm. t97~ 4 E L Wynder K klahuchL E I Be~uie Jr •2 Am Med• A~v~ 213 22~1 (1970); L D t~ross and R~ GibsOn~ Ar~ J~ p,,~&, Heo~th ~1, t396 (196g). 5 E L Wyader and D Hoffmann• J ,'4a. Can eer lnl:~ Sit 513 ~19~i i,~ b~perime,md Carcm,,g~e~i~ ~Aea,lemie ~aess Ne~*, ~onq 1967L 7 G B Ce~i,S P I$~niita, P ,t,~ Tha~er "M R, Guerirl, C ] L~n~h~ (fiem~tlr, and In Vim~ B#,a~v elf Smoke fro,,i Ev~,,r~m~.ml elan rette~ [)HEW Phil !N[H]76 1076• GO~¢IT~ m~l J~n n~iog (IfB~e Wash nyto~ D C • J 975/. nin~ ]. Sk~i~t. P G~ Here/d, Eds (Amefica~ Chcmmal ~ciet~ Chemical Mm kefing anti Ect> nomi~ l~qston, [~m~kl~n, N y,, 1975), p~ 239; D F Ms~zlnger atld F A. W~m~mam in pro ceedi~dr ,~f ~he 51h l~ternallona~ Toba((u St; e~e L ~ng~e~s (llamhurg~ [~70). p 6g 9 E~ L '&~nder al~d D~ 14~ffmtmn, N~ L,,gl J Med 262, !4@ {/963L IO~ D V¢ D¢]ol~g,J Lam~g [o~e,E yod~r~T~ C T~ Be~l~ Tab~&lorlch~ 8, ~3 (19751 II G B~ G~n, m Proeeedlngs ~f Ihe 3rd ~orld ('o~feze~ce on Sm,,M,~g dad Health ~ E, • Vein der I~ Hoffmann, G B Gun, Hd~ IGovem raenl ~nlJng tSgfice• gea~bJt~gllm• D~H 1976), pp~ 451~L /~abek/orw'h g 4~ (]975); W, H Iohn~on, in 5 c~em:e Co,tgre~s ~Ham~uxrg~ t970), p t4L 13 G Re~nlk, H Rezrdk Sehullev, H Scho~lek, K Depp~ U Mohn Arz~e~m Foz~ch, ~, 923 0975)¸ 14 ~ Dolt en',~ilL H L ChcvalieL H P IIzrke•U C,iacer bra/ $1, Z?~I /l~7~l~ 15 "~. F~ntlrt,vilI, H j Che~aller, II P Halke•H J K]lmi~ch• U Lafr~nz, O Re~kzeh, B bSeis~ma~n W Keller• Z Kreb~forsch ~11, 236 (1972) Ita~ardous C;gar~rre~ ~he/-irst Set orE /,er]~ mental C~gare.e~ DHE'& F'ab tNiH 7~ 905~ Government printing Dffic¢~ ~a~llh~mn. D L ~, 1976~ tL 14 M H,*[~erandT~L lto,J Naet (aneer~nst ~ t8,5111972}; D Hoffm~mu and E I.~ W%r~der, ibid,~ p 1955~ E I. Wy~der ~nd D~ H0ffmanm J Am Med 4~$o~ 192 g~!196!) 18~ E [ WynderandD Hoffmun~,S~ie,tce 11~, g62 U9681 zg, C / Ker, sler ~m/ $. P Zta~osta, :;~" A,,% Re,pit U~¢ '~3 93 966 ;~'¢ ~,t¢1 J Med 269• 1161 (19631¸ 20 O. Au~rba.h E C H~mmond• D Kirmall• I Garfi~keL I~ ~A ~t7 Syrup Set Ig, 375 !197()}; G FreemoJL S • trine, N~ ~, FuriosL R L Slepht as. M L Evarts~ W~ ~ Mutate ~m Rev~ RerpJ~ D,s 1~i~ 563 (1972) 21 U $ Public Health 5emlce lturmfu~ Cons:ilu. t~ e~t~ ef C~gare~te 5mu~e DHEW p~lt,~ !HSMI72.7516, Gover~mertt pdntn~ Office, Washi,~loa, D,( • 1~72L p 137 2L S S Heeh( and E L 'a, ~der" in Pr.,'ee41ng~ oJ 'he t,d 19otis Cor{fe,,enle on freaking and f~ Health, E I ~. nder D ~offmanu, G B God. gds (Gover~mem Pan~mg emlce, ~,ah i~g~,,~, D C Z976/ pp ~92 202 H P .~egge and J Bolllqum Bettr la~a~for$ch ~, 21 ~ (1~1); K D Bmnnem~nn It.c lee D. It~ff ~ mann, in ~revaration; S S ItedlL R Tl~0rne, R R Maron~ot I3 Hoffman~ J ,',,arl C~ncer 23 S P Ilatfi~t~ Jn#roceedmg~rth~,Jedl~'orM 124S

der~ D H,ff"n'ann~ G B ~3on~ ~d~ ~ ~,cm ment pnncln~ Of~e~ ',~,,blnglon D L~. I~¢,L p 517 5?4; -- and C J Kcn,IcL ~r,~ Naff~ Cancer /n~l ~0~ I~1 H~72k ~ A~ M~T tell ~,r ~ i~ ~3 404 L[97~) ard. p G ScniIh K Kjetd~em ~, ~cd J l N ~lrauch '~ J I-~rlu[n J H Keelso~,Aeln 2~ ~ S ~rnn~w, ~e, ~d ~ 952 [197~); ~e~ Me#~ 74. 69~197~): ~( (~reen,p~n ~ E lern Med 1~3 ~07(1~59L Feye~bend p V C~le B, ~¢d J ~ 4[4 11975) 2~ N D Bnlnn~mann ~nd D l~offmann ~bod 2~ H Sch,evelbein ~d l~ Eberh~rdl,y N~ C~ ~moktng and lJeal~h p~u~r,~m Ss~r~s /~e~,~tt (National Cancer lnslilUte ~ethcsda M~ Ja~ll 3Z Four ~c,urced~urncn1~c~,mlJne~ surnmar~e of the ~la~ a~ed to compute ~he critical value, of ~il~ clgareltt eoe~umpU~)m Follo,~ h~g i5 .1 llsl qf Ihe~e d~,~ume~ts the ~udte5 wlthL~ eac~ ~ocumem T~II? were LI Se kl TO ~Ompute 1he ¢1111~aJ ~alues and ~lle result ~ ol :he ~mpu~atlOn II From Smokln ~nd heNth rep~rl ~rllw Adv s~lry Cn~ mlt[ee ~o [hc Surgeon ( enera e the PUblic He,It h Se~vi~e " [U3 Publ( /~e~#h ~e¢~ p~bf 1103 {19~h4} p~ 89 anti 3241 the • ,~s 3 m 4; for mol~aliE~ ~rom all cau~c~ ~- nnalc ~,lr~nt .mok~rs CV ~s I ~o 2 ia a ~t~d~ ~f men in n~ne ,l~es ~J ~ I ~o 2 in a s~udy ~I U S ~e~eran~ ~4). ! TO 4 in an ~¢¢u~aliona: st ~1~/y in C~lifornia ~35). ~nd 2 t~ ~ ,n ~ s~ldy ~f men ill 25 ~ille sta~es [~L 3 m 4 ~r I] S v~tcrans ~41 Dnd 4 tn 5 fnr r~en in 25 ~le ~ (J~ _~ I-ram -T~e hea~c~ ¢o~eguence~ of ~mck i~g ~ Public lteallh $er~i¢¢ Fe vie~ 1967¸ IU ¢irrhost~ ~f the liver¸ > [0 fur cancer oF the (?7): > 10 ~r cmphyserem bronch~ti~ ~r ~rh in 3~ F~m The healltt ¢~qacnccs of ~m~k ]n~ a r~ >~ t~, the Siirge~ G~ncra/ 1971¸¸ ~OH~ ~ub!, IHSM, 71 7!13 IJ~7[) pp 2~1 ~3 286. 299 294 298 ~mi !f~) ( V ~s 4 Io 5 1o 2 for hm~ ¢~nccr in U S v¢~r~n~ (~7); 0 7 ~r (41 I: 4 1o 5 fOF lung c~n~cr i~ ~ 2tli f~lr n~:, malc~ I~2 ): arid > l~ for Junk cancer ~ J~pa.~ mak~ ic,n ~LldV t96~197~ in l~r¢ ,) ~r ma[~, •V wa~ t~ o~K~¢~b~rgc~pe[ungcancer ,~9 ~or Kr¢ berg t p~ 11 lung cancer ? c~ 8 ~r ~ancer of the ~ral ca,~it~ > IU or cancer o t c I~rynx > 10 fc~r es~hage~l ¢a~¢er and ~ 10 3? Whi~e ~e.~an m~le~ enrolled by ~hc Ame~ ~a~ Cancer S~ie~y in rlilk¢ ~tal~ [E E Ham ~4 V~ter:m~ ,~ho ,elvc2 he~cc~ 1917 ~cl ~0 and ~er~ ~fi~ ~ hOId~r, O~ L~ $ g~,vem menl I,~ ~5 Men 3~ t~, 64 ~cur~ old m ~,n~ ~c~J~tllun, in 36~ E L Hammond a~d J Lamn~L Arc,t ~ ~9 A J Wickc~ h,h R~, (~)~r R,x p,~ 9 I t~,) 4O ~ D~IJ ;~nd ~ B Hill ~/r ~,/¢d J '*,, 53~ 42 J H W~ir;mdJ F Dunm~h~l 25 I~S~l'l~0) Fpid~rn~l~og~ Division fokyu~ September 194~L ~naJ~zcd ~e/~lralely ~r c~ch ,~l~y 1he d~a ~ilh ~c number of cigar u~es ~on~urled d~dlv: for exampl~ I.r n~ ~ig:~rcl~cs the I~bliv~ li~k Io 2~ ¢iK~rett~ 991; ~r 20 ~ ~9 dg~rctte, I~AI: a~d f~r > ,~o ~ i~arc~c, 21 ~ ~ lru r ,*>me ~mdie, the ca:egori~, ol d~]y ~ig~le~ e~m ~mpw~n 4iff¢c~d from the,¢~ ~ used in I~e ca~culati~>n. I bus ~r ~he e~ relative li,K ~ 9 ~1 ;~nd ~ ~r~h When ~b~ ~i~hes~ da[l~ c~n,ump~ion v~l~e wa, c~prc,,e~l ~s ~n ,~-~<~ed h ~t such as > ~0 the ~raphicaJ ob~r~ali~n and ,frm,~al an~,ly,i, ~g~c,~e~l thai 1he gJ~drad~ function ~Eq II c~ampJe~ 1~e ~rre~tcd malllpl~ ~,cmcient of I~ 0)93 ~ * 10 9~3 × i~1 ~,~ {2} The ~lc ×~ ,~p ~n ~h¢ analv .i, ~d • C~ ~U]¢U a~e, ~r ~a~h ,~Jd~ the I¢1•~ ,igmficaat dtff~'rcncc E~rnaTcd rci~rlVe ri,k~ ~cre compu~e~ from ~nd 2 ctgu reties Per d~y 124~