Tobacco Documents Online

DIETRICH HOFFMANN Leading authority on tobacco carcinogenesis, biochemist & longtime collaborator w/Ernst Wynder ... interviewed at Amer Health Foundation in Valhalla NY 5-31-91 --------------------------------- ° -------------------------------- --DH & WYNDER (EW): Came to US as exchange student in late.:'50s.at Sloan-Kettering where he connected w/EW, a physician, where DH H was a biochemist so "there was no competition" bet them...~H was a lab man & ET+Twas "a sc' nce m r` administrator & strong in personnel & by his early 40s didn't want to do research but carry forward his chief conceptual idea, promotion of preventive medicine in chronic diseases... the assn dates to ':"'n1e are uite different thou ou are t e same" both have pronounced German accents, DH s more so'& some have suggested the pair like to maintain the accents by way of distin- guishing themselves from the less learned Amer. scientific community), adding "He (EW) meets 100 people & likes 110 of them; I meet 100 and like two of them"...says there is great mutual regard bet. them//EW "has an aversion to extremism," not the sort who bashes people over the head...a refu ee from H in ' O son of a Jewish h sician in the Wes H (check EW's bio , his father active in the local tennis club & prominent yet perceived as left politically, the family resettled in NJ (Irvington) where sr. Wynder resumed practice... in the antismkg fight, Ea put off by extremists like Greg Connolly, who . is very bright but vociferous, on the barricades...E'rJ more philosophical, knowi "We can't kill the tobacco industr " so let's see what we can do to mo £ its excesses...maybe there is a mtg ground on I o of the issues e science & the profit motive, so let's explore that common ground...EW has "a balanced view" knowing that people will continue to smoke the legal product so main thrust is to educate & maybe modify the product...to learn the why of S&H and do so in a careful fashion, n_o_,tt._ like Gio Gori, a bri~ht man "who ove la e P.Rrdbelow) be- cause e was so convinced t at lowered yields were the answer & made the mistake of e o t u' s in iel W DUE REGARD FO S TION FAQrPOR -- " ' b c us '- ai1 he GG was a good " but -rj2" aeX~Qd . pp., . .,g'~o;.,C:OV//add EW'S PE~SON_ •AT TTY• T N brandse are stil l toxict e "~ s"an~~''i i'SSa~or u~"doesn thave e atlence now to slt agym ttend to the detai s, t a s w at he has a s a or...can seem aloof & dour a imes but is reaIly somewhat alzstracted...NOT AS TOUGH ON PEOPLE as DH wo be, very tolerant, stemming from the experience of his youth in Germany, hates discrimination ... has said to close colleagues that N ~w "I've had the two best things you can in life -- A GERMAN E_DIIC`ATIO AMER3~OPORTUNIT%" but has been advised not to say this too loud slnce Amer academia not appreciative ... a cosmopolitan man verv u'~^o-r~, omewhat liberal in his politics, given to a certain flamboyance in his personal i e s e a many sexual affairs in younger days though has had a longtime companion in recent yrs, never quite trusted himself or seen too many marriages fail...AHF started w/4 people & now has 24-0 w/ locations in Ford Fonndat,on bldg in N small Westc es er campus --EW & S- :'s work much s d s directo -- to the p-L of consenting to aving his baek painted w tar condensate, saw early changes & did biopsy, back got very red & allergic reactions began, ~ this reported in the literature -- BUTs things changed considerably when Dr HORSFAL became S-K director, a hvy drinker & smoker, a hi~h-liver who ~C was also aTiologis wou conce e no more t an possible minor Sink bet O~ S&H, discouraged him, raised mone,y from tob. co.s, $2 million grant from ~a RJR & also PM solicited...~hfJ-as~ce for & got a special review committee -A of his work which Horsfal couldn't deny & this strengthened EW's hand but ~ Horsfal nevertheless ke t cuttin EW' t& after one 5% slash too ~ many, W gu1t...was urged by enno Schmidt, S-K bd heavyweight, not to N but EW did anyway & never did get put on S-K bd in later yrs, unforgiven '~ --DH'S MOST IMPORTANT WORK: His people look w/disdain on sensationalism & concepts of quick public notoriety they dub "C_arcinogen o£ the Week" & "Breakthrough of the Week"...they've stuck at their wor onger than any- one & remain fascinated w/it...U million or so Amers. still smk when first SGR was issued...once early on he submite a study to CTR & got the grant application back withim days but found two co.s had the idea patented post-haste so he steered clear of the industry ever since///te ork has been PROCESS ELIMINATION to narrow most lethal d er...early on foun hat the GAS PHASE DIDN'T PROMOTE TUMORS IN LAB. ANIMALS so they concentrated on the tar particulate, yrs spent breaking it down to d.termine hich com ounds we st in tests on mo , rabbit ears, S; OLATING fractionating the Smoke for separate elements, see key '59 paper as a

hof£mann/3 Vi sl mfi' as even on U indiv e ua T a.smiss ese small dos es per. v - cS~ bo 's de enses & wat,e war on the dy s susc abila.ty can wear down the s r se -a user Ch`LL-T~ , mouse epidermis vs. lung epithelium, the more a.gh y ar ..cula~ complex lung tissue/cells revert to mor rim- itive form after bei~~n ~assaulted by tob. smoke in pre-me ap asia phase so -EFSv ~a~p~ et~i v are similar to mouse in early day~&~p.. "'didn't look for nitrosomines" & when they did it was hard to hold them during the f`ractionating process*****came along in early '7Oe only... TWO KINI~.S OF CARCINOGENETIC ACTIVITY: (1) contact carcinogens, as via the mucous in lun~, a fertile field for growth & (2) organ-specific as with nitrosamines//PM's "Next" denic brand: after reducing tar levels & ex- tracting tracting the f avora.n , a o put the flavor back in to lower yields & the spr sim 1~ restored the nitrosamines taken out (RK: not sure if I have iatF`s rig - so am wrag ing tor e a o a on ...some of the additives were carcinogenic, DH found (eg, deertongue contains cumarin so no good, but others tested didn't show carcinogenity), turning to synthetic flav- orings --ARE THERE "LESS HAZARDOUS" CIGS, is the concept possible?: DH wary of the terms..."The industry could do a better job in producing LESS TOXIC CIGS" & he himself thinks YES it's ~oossible to modify the aroduct in this way, cites Stellman-Garfinkel paper showing clear correlation in Illstrength of the assn & yields...DH concedes he can't tell if "safer" cigs would sell, be palatable to smokers -- A DIFFERENT QUESTION...but he has hh regard for the industrv,_.'~k-i11s but "THEY ARE A LITTLE DI3COU~C'R G~D" that a modif ied product can sell, safer may equal less desirable in re taste --E'ia EVIDENCEs He thinks comparatively only it's less of peril, to be sure, but oompared to VINYL CHLORIDE & other substances that 1ci11 a few I~undred & cae gr.eat alarm ETS threat is by no means underestimated or dismissable...recent new study from France sT.ows that children exposed to ETS by both parents grow up w/far greater L.C. susceptibility & other di- seases even if they don't smoke//note that SG KOOP OVERSTATED THE FINDINGS of his scientifie advisorowho were very cau$ious in rSb writings but SG's summary not that wav, DH asked him about it & Koop says as a public ea1i th officialT he hd to be more forceful in indicting the threat...sees Koop as a vrohibitionist;by tendenc~r...DH calls ETS uproar "A PUBI - HEALTH STR_~y"~c poli~ical3y very effec ive --AUERBACH & HIS BEAGLES: "Beyond corru ti~on...a wonderful human being" . who did "FANTASTIC PATHOLOG3~,~ w~ isst ue ~~I wou7.d not have done tFie beagle study" because you can't get dogs to inhale the same wavuthe- ~ tracheotomy c.n't replicate even so he c7;d get some lung tumors so the ~ s yytd-was ev~.'3ence & indicative but ou can't dr om ar:.sons...the ~ earlier work considered far more impor ant & inhalation studies "never ~ gained much credence" as conclusive ~y IV O~ from top job)...JIM CHARLES "nice guy" but not in same league w/i-IW, nor was HW's successor Robt Seilgman nor his Swiss successor; Charles is one of few left who still smokes; Alex S ears ci than HW (in DH's opinion), quit sm R... ENE. NOT EASY TO HANDLE, would cu:E off lawyers to have his say...Lorillard led the way w/effective filtration w/Kent &"micronite"...PM seen as most far-seeing of the co.s, AmerTob as most short-sighted, failed totally to get into filters early & effectively//WAKEHAM AT NCI TOB. STUDY GROUP MTG in which Shubik yelled at CTR's Robt Hockett, an inoffensive little man, £or stonewalling & denying (see NCI files for notes on this mtg) & afterward Wakeham told off S~hubikj. to the effect that scientists shouldn't a to eac o er in such emotional outbursts, inappropriate behavior (and DH agreed, though not sympathetic w/tob. co. position)//HW PERSO . =e_"Teutonic...gets ~ ri ht to the tt can be uite eterm e, a ey p ayer, r g-- man f1A e rig ime, ui e-prograal...the kind who might say "You don't do much, but what you do doesn't make sense"...A LOYAh CO. PLICATING HUMAN SMKG EXPERIENCE IN THE LAB: " ou can t reproduce the human se ing so t e nurnose o e bioassays, even w/their vastly greater dosages, ~s to trry to understand the tumorteo~;enesis procesa, to try to get at te_ mechanm& not metcee immediae Jum~o hu ans in terms os & th 1ike..."You don't have to du licate'r the human smk e can' o eriments w eo 1, now more sop is icated ways of determining likely effects thru markers in the blood...we know that some of the nitrsomines are very powerful carcinogens, like NNK, which at one part ver million in drinking water is lethal...so only a ~i S VEIiT BAD-F-c o. industrv can't bli inconsequential; cumula v thev ua11y, dependin

. hof£mann/2 MAJOR EARLY INDICTMENT of carcinogenic elements found in smoke, showed industry benzo(a)pyrene among the aromatic hydrocarbons (polynuclear), UNSTABLE COMPOUNDS THAT UNDERGO CHANGES DURING BURNING PROCESS & react w/each other...alone individuall the c ot account for th arcino- rJO+As+s but but w en com in~d, these agents w high potency produce high tumor activityv..these substances are co-carcinogens or promoters, a diff. but related category of substance///need to determine which of these TOBACCo-SPEGSFIC SUBSTANCES do the damae~e at doesn't occur in other plant pyrolysis, eg mariiuana doesn't cause cancer p rt of it likelV due to NICOTINE & how it relates to tob. alkaloids...NICOTINE= A TOXIC AGENT. not a carcin~en...something in that blend that GIVES RISE TO TOBACCO-SPECIFIC NITRSOMiNE , key carcinogen...NNN & NNK found only in tob. & very powerful carcinogens when tested on lab animals & producing lung cancer WHEN METABOLICALLY ACTIVATED, integrated into human or animal biosystem by intravenous injection or water or skin-painting, once in touch w/DNA they ao_ to town_...ENZYMES ACTIVATE THE PROC & these are ~Y CONCENTRATED or present in e UNG..G od s defense s stem doe H_ it b t th be d discard most of es . after e' o ic eptive territor_v 1ow MUCOUS T O SETTLE & thus e 0 ~ a orovie~e-co ec sm ~~or the tar...isoenzymes they 're -oalled...strong reaction w/DNA...you can achieve these effects w/human tissue of lung taken within 4-6 hrs of death via autopsy, seeing how tar distillate qualitatively metabolizes// ANIMAL STUDIES IN U.S. VERY EXPENSIVE & difficult to undertake because of political sensitivity to humane treatment...work should be done w/ primat~e_s~~...OK to use small animals w/2yr lifespan like mice to get sped-up reaions but very difficult & costly w/monkeys that live 3Oyrs...WORK W/DNA SHOWS: NATURE CAN REPAIR SOME OF THE LESIONS (& probably does w/ less active smkrs & quitters) but the constant hit of habitual smk (adds Hoffmann's wife & co-worker wears own is defense mechanscm & PROTO-ONCAGENES GET ACTIVATED,~`inducing big trouble...REPAIR ENZYMES ARE EVENTUALLY OVFR['.OtvtF, defense mechanism collapses -- HE CULLMAN RATIO (tell us what the problem is & we'll get rid of it : inl this is extremel naive & disin since smkg ' has been "QAUSALLY ATED" w cancer in 7 bodv sites: mouth, laryns, esophagus, lung, Ti ey, pancreas & bladder & possibly w/other sites (see EW's epidemiological studies for this)...plainly a complex problem & pro- cess & the damage is undeniable, so naive to think ther ' "it" th t si 1 can be lifted out from the 4 00 or so com ounds man combo ic r er the is s r s...many diff. agents & components an the smoke -- as JosII2 must know; P.d does much of its BIOLOGICAL WORK in its European labs~ not in US. where only chemical analysis is~, thus to protect biological work from possible su pena...NO OTHER COD'iBUS- ~ TION PRODUCT HAS BEEN STUDIED IN SUCH DEPTH for obvious reaso ns...the / 1 1n us ry abs were"litt e bac rms" in the early days but now co.s do a lot of sophisticated research using superb equipment -- but not in the biological area (RK: they make the link inferentially via lowered T/Ns as less hazardous)//CITING HOW GENERAL FOODS DID DECAFFEINATED COFFEE, ran into some early hazards w/FDA or other govt agencies on "super-crit- ical extraction" of caffeine...PM buys r~-rj,es to analogize by remov-_ ixtP' NIC from "Next" bran_d, roblem a.s that you take out flavor in the ~ process & inrestori it w/concentrated spray, the NITRSOMAINES WERE PU.T !!! BACK IN_*'j''*'*'~''#''~"""'~"~'#~/£e els'~''#"""'~"~'#~/£eels that tob. co.s withTir ingenuity could in time achieve useful improvements by adding via synethetic flavorings enough taste w/carcinogenic potential to reduce the hazard -- w/o ever saying (by DH) that what is left is "safe"...RJR'S PREP~2IER= MOST OF THE ~G MONEY SPENT ON HINER oduce lOM a minu e of com i o= mec anica terms "A MASTER_P_IEGE" -- BUT: they rushed it to mkt w o over- ~ coming the iTF7, R PROBLEM &(2) DRAW RESSSTANCE -- "The um ed _~the ~ gun because Philip Morris was gettin~ ready to go into tzle~~k~w.Li~- ~ T7-~ RJR SC NT 1 RE VE ran RY UNHAPPY"//DH says ~ he's not famihar w/the PALLADIUM CIG but sees analogy to the flavoring ~ problem & need for more additives via Burley which has more nitrate & greater peril of nitrosomines//RJR spent maybe $200/300 million on Pre- mier w/most of it on the engineering & mfg --HELMUT WAKEHAMm DH im ress d b him as a fellow German-speaker... had expertise in area of the cellulose ace a e i er since e d worked in textile field & research...infinite variations in how you crimp the cellulose, what denier, ete...PTJf needed a fellow w/background.~tin'.biologic n sciences as well & HW enlisted Dr. THOS OSDENE frm nrtn 4rir7ercon an er Center, considered something of a loose cannon, not so politic as HW ~t so de e rential to lawyers "who run the tob. business," so he never got the top rsearch job (RKi by definition, his specialty eliminated him

t hoffmann/4 --G1O GORI & WORK AT NCI: "Very bright -- but he overplayed his - ---' ' b cards," was a^driven" m o should ve o; aws & anvroach.._. . Y_I_VDER TRIED . n , quantitative e4ui,v,a}e.' .. .,.. ~rom reg.-c"gs"-~o"filters via tfie"' vields "but he was so convinced of it"...ran afoul of Califano --CHD VS. L.C.: DH thinks the heart side of it is less of a mystery obvious//CO promotes TO WARN ot to vublish his artic.le HIM i P11 0 ku emne LO 8I lU & ts was das~~arAURo ' to tfy"to transla w~ NVE than carcinogenesis because mechanisms seem more heart disease b robbi s stem of nutrient that i have -- ox en -- k h d to r er uer~y~.ng i e achieve the same effect w/less oxygen present + NICOTINE nromotes -o1aeue buildu & fatt acids via catecholomine re echanism...these less complica e o DH t an cancer process --HAS INDUSTRY MODIFIED ITS PRODUCT: In a word, yes -- which is not to say that any cig isn't toxic, but relatively, yes...see recent Stellman paper ('89) on numbers fr' om '60s, "a beautiful study" that makes no effort to deal w/"compensation" (RKs but those yields had low-tar then at -17mg th £uel muscles need to opera e, so it has to wor a LATE ARTICLES STRESSING IMPORTANCES OF NITROSAMINES.... --ADVANCES IN TOB. CARCINOGENESIS, Hoffmann & SS Hecht, from handbook Chemical Carcinogenesis & Mutagenesis I(1988?): Tremendous jumps in cig production in less develo~ pe~d nations, in '76-'86 decade China up nearly 85%, Egypt 112%, Brazil 4~"~//BURLEY LEAVES have relatively high nitrate content & the hi-fi blends & some w/flavorings added may be using still „ more burley than in past...TO$. CONTAINS 2~550 KNOWN COTJiPOUiYDS...in ~ France arts of Ital No Africa & South America 1-b ~.~ burle brands are n ver i major constituents in vapor o mains ream smo e listed on p 7e CO=2.8-4.W. of total effluent//constituents of particulate matter ~ (tar), p68/i.ncreasa.ng popularity- o£-.Low T/N yields because flavor addi- tives made these products acceptable to consumers; these compounds derived from tob. extracts or other plants or synthetics, but no telling about the ingredients since held to be trade secrets -- however it's known that ~7~(Z mfrs in many countries have discontinued use of COUMARIN c rcino en xcvrs_p,T3 in rats//nic. reductions haven't been as steep as for tars SELECTIVE REDUCTION OF CERTAIN TOXIC & TUMORIGENIC AGENTS HAVE BEEN ACHIEVED by cellulose acetate filters, reducing PHENOLS & VOLATILE N-NITROS ~' + 2er£o ted filter tins by diiution w added air ave re uced CO & h~y~dr~~es~ QY IDE...Charcoal~capable of selectively reducing vo.latile al,,.ez yc ktes_;~~c h d ro~~~ _ i e f use 15P ~ecd3iSt3 tt)teQ Eof , expanaed_ tob & tob ribs has led to~RED_ _1ObT=.O~`."~~LYNUCLEAR ARObI9TYC T-IY`NAOCARBONg ~N !'I-tE SMOKE;` when tars from such cigs are tested on mouse skins, there's a reduction in biologic activity for same dose... inco s& steme into i bl & utilization of more i ties as cig fillers have caused AN INCREASE IN IYITRATE, COIy,TE.~iT ~ofy:the Amer blended cig, so there's ....... ..--.~1 been a traile-o££ but not nec~s~arilv a net'-ain"in ca~csn_o~PriP +******71// see Ta e 3972 for tumorigenic agents in tob. & tob smoke & IARC eval- uation of carcinogenicity in animals & humanse see esp. benzo(a)pyrene, nitrosamines as adequate in animals for this bioactivity, aromatic amines, ~ benaene & vinyl chloride, arsenic, ahromium//PAHS by themselves do not account for tumorigenic activity on mouse skin; these are known as "con- tact earcinogens," 75//see NITI ~OSAM~I_NE~Si„stqr-~.2b:x,-._high carc_„3~,ggex~ic ote~ncy_ijoted iI}_jn~,e.1j cavi y o`~.rats. lungs & trachea`tigod.en hamsters '& lung tumo'-rs-~n micer~3s or~an-snecific threat to the lung, esp. bad also, w/NNN, for oral cancer TSa '8 SGR & ze d that nons living w/smkg spouses have about 307T'igher 1.c. risk than nons living w/nons, but this challenged, IARC considered the epidemiologic data to be inconclusive thoueh concedes there is some i'~ ei~F' ene r ue to known p ysichemical nature of tob, smoke...HIGHLY SENSITIVE CHEMICAL & BIOCHEM- ICAL METHODS ARE NEEDED TO ASSAY THIS EXPOSURE & THE UPTAKE OF TUMORIGENIC AGENTS by nons//°~emarkablv hi~h" release of nitrosamines & aromatic amines in sidestream smoke noted by many inves~ti ators `*`***•'""' and filters & other modifying agents in cigs have no e ec on n this since the S/S co es from burnin end + "on a gram to gram basis the particulate matter of SM is ~ more carcinogenic on mouse skin than the particulate matter of M/S," see C7~ EW & DH in for Steinfeld's earlyv warnings/BUT: see b85 for "The concentration of toxic agents in ETS ap- -' ~ pears LOW BY COMPARISON W/THEIR LEVELS IN UNDILUTED P4/S, but one needs tocr% \~~'JJJttt'lll take into consideration that the ACTIVE INHALATION OF TOB. Sh4OKE IS LIM- rl-') ~ ITED TO THE TIP.1E IT TAKES TO SMO , w i e the invo untary in- v a a ion o E CAN C UR OVER 5EV HRS EACH DAY," a fact reflected in

hoffmann/5 ~ uptake of nic. by active & passive smkrs as measured in blood serum & J urine of passives smkrs, it amounts to about 1% of nic in ~phrysioloa3_c ~uids_of active smkrs, but not • sa.gni~icant in COHb= t ere is "a great need for o er 6''Tological markers" to determine prevalence of toxic effects in ETS//see Table 6_for ratio of bad stuff bet M/S & S/S p86: in benzo(a)pyrene it's about 12.pof n'i S, & O7, o to pic two of the nastier items ... stressing w/PAH key role of cocarcinogens & promoters, see CATECHOL as classic cocarcinogen when interacting w/PAC...see marked graph on 89 for cellular effects of smoke condensate, the subfraetions . affect "growth, morphology, epidermal growth factor binding, & causes SINGLE-STRAND BREAKS" in DNA...NNK causes INHIBITION OF THE REPAIR ENZYME in lung DNA durins chronic dosine, K ~-also signi i.cant tha e repair enzyme is inhibited by acrolein & other aldehydes which occur in high concentration in cig smoke (see Krokan's '85 study**'x"x'*'tt'#), 90... see p92 for .~NA DAM~C~E INDUCED BY• UNKNOL•,1N CONSTITUENTS nF m0'R- SMOKE, talks of exceedingly sensitive bioassay app7:aed tp._DNA isolatedrom placentas of smkg & nonsmkg mothers & has shown present of tob smoke- related DNA adducts, also observed in the bronchus & larynx of smkrs... ~ below, "Cig smoke generates active oxygen species such as hydrogen per- oxide, oxide, superoxide radical & hydroxyl radical (which)...can induce single- trand breaks in human cells or cell-free systems," etc., STUDIES IN MID- & LATE Os showing more more c ues as to how the cancers get going --TOBACCO-S ECIFIC N TROSAD'IINES AN IR'iPORTANT GROUP OF CARCINOGENS IN TO . B. SM9Iii!;by Hecht & Ho mann, Carcinogenesis _~: rst anal sis off tob.-smoke for tob•-Specific nitrosamine was renortert in ' ~re•#~r#levels ~'-to .-specific n~s in tob. products-''ARE REIvIARKABLY HIG THAN THOSE N'S IN O CONSUMER PRODUCTS " see those in bacon & beef reeulated bv USDA which cannot exeee parts per billion whereas unregulated n's in tob. are foundin the parts-per-mi ion range, see dose in snuff is u o O 000 TIMES I-IIGHER THAN LEVELS REGULATE acon o *"~*°~permission o suc evels of n's is B7AJOR LEGISLATIVE FAILURE"#"**tR877. .10o0Y greater than benzo(a)pyrene in snuff...N_s are ot reduced in lower tar ci the or~anos-pecific'~,ty of NNK for the str un~ is ?kina."bR~ RECENT IDENT ATION OF AGENT WHICH COULD INHIBIT TUMOROGENESIS by NNN & NNK is important re cancer chemopreven- tion: isothiocynates are broad spectrum inhibitors of the metabolic ,' activation & DNA binding of NNN & NNK, bL878...these n's require metabolic ~ivationfor binding to DNA...studies of this meta o ic ac ivation noted, th O, compoun s orming "macromolecular adducts"...new insights into the mechanisms by which DNA is modified & cancer triggered...pertinent levels of the repair enzymes may play critical roles//SUMMARY & CONCLUSION: these levels of n's represent "an unacceptable risk to tob. consumer... see strong quote here o'n EL-SS2- o~-ee ".-('L evels of to .-spec~.fic n's in tob. are thousands of times higher than the amounts of other n's in consumer products that are regulated by govt authorities"*****"The dev. of assays for quantifying the metabolic activation of of NNK & NNN,has led to the discovery of compounds which inhibit this process, most notably isothiocyanates.... --LUNG CANCER & THE CHANGING CIGARETTE/by the Hoffmans & EW, IAR Epidemiological studies have s o~t lone have 20-50% lowe -term smkrs of 1ow-viel b~-. r ribsk of l.c. t an h smkr of high ields/"Although a smoke- free society should e the maJor pu~7.3c 7 ealth g~ecent consumer sta- ~p ! tistics do not support this goal. Thus, a strong social case is made FOR ~ FURTHER DEVELOPMENTS':IN THE LOW-YIELD CIG.... in developing areas in world ~ cig consumption was outstripping pop. growth (excepting Europe)...T/N ~ ields in US UK & FRe German bet '60 &_~had fallen $5-5OJ (fo+^~"~?~s, O~ nic off a bit less - /TEC . E4'h'LbPMENTS: T's can be reduced no ~0 more than 50 conventional filter tip because of draw resistance beyondtv that but can ~ wremove p O o certain volatile smoke components...then ~ u to d~ S- elp perforate i er ips dilute it even more..& e~c ven though avg cig length has incre wei ht tob t ical US ci off fro 1300 m ased, av in '40s to 750 mg in 2eLSsti u$oT. r3cbs &' expanded tob. (fillers), see t453*~#~*~~~#~3`thi s ~*~~~#~3`this . is v ood summar o • CATION PROCESS//COb7PENSATION, b453, but not entirely, see IARC study of '8 SEE 55 for OII~IPOSITION OF TYPICAL US BLEND CIG (flue-cured leaf 32%, burle 20 2, Orienta 10, ste 2 i casi , avors- umec an s ..see Ho mann study of drop in one.NON-FIL R~~ CZG from '58-'79 showing drop in benzo(a)pyrene levels while T/N in this cig off 31% & 39% respectively, benzpy. off 56%//HOWEVER, in evaluating preventive strategies that involve product modification, must monitor not only for specific indicators but for the overall chem. compo- sition sit7.on of the smoke..,use of N2TRATE-R-LCH TOR. A: RTBS TN('.RF.ACF:S mHF PQr N- tl// TIAL FOR H ar-rFR SmDKF YTF•r OF mOR-Sp CIF2C NITROSAMINES tha-t are hiShly carcinogenic in some test NYT edit re Premier urging further product modification & that '..the best should not be the enemv of thA voo~l"