Tobacco Documents Online

P!,ir;:FG'6V Mr Cuhr- I I-p"PI iI^;, Har r, s `1V :n 1953, wynder ano his group reported that repeated applications of cigarette smoke condensate could produce tu.;,~Mrs on mouse skin. Shortly after this article was published, Liggett t N.yers established a contractual arrangement with Arthur D. Little, Inc. The o:jectives of this joint effort were to determine the va_idity of Wynder's results when the appropriate smoking condi- tions were used, and to determine the effect of different types of tobacco on the response level. An extensive program was also directed toward defining the nature of the material responsible for the tumorigenic effect. E+'ynder's findings were confirmed and all commercial cigarette types produced virtually identical mouse skin tumor incidences. The tumorigenic inltiating effect was four,d to reside in a rela- tively small smoke fraction containing the polycyclic aromatic hydrocarbons. In 1968, L&M initiated a tobacco additive program designed- to reduce or eliminate the tumorigenic activity of cigarette smoke. Once the reduction in tumorigenicity was achieved, the next step involved the development of a commercially viable ciga- rette. The research efforts were then directed toward the compi- lation of evidence providino assurance that the tobacco treatment would not introduce any new or increased hazard to the smoker. Although the only meaningful test capable of ascertaining whether tumorigenic activity had been reduced was the mouse skin painting test, time and monetary constraints required the develop-~ent of a hierarchy of chemical tests indicative of actual tumorioenic::y. B. JOHNSON 24'85 ... ~~ YUVOSf ~. C T R 1 --1 N 0:' -2 8:2 4 1

;:.is tes thiera: chy was used to evaluate additives selected or, t-e basis of existing tecT.nology in other fields. The most pronisin: tobacco additives were thern evaluated in act-jal mouse-skin paintinc experiments. The reduction of the tumorigenicity proved to be a rather arduous task. The development of the chemical tests required about 15 years and the screening of potential additives took about 5 years. In total, about 14 million dollars has been spent in the overall development of the XA product. After evaluating more ttian 200 aduitives, the most effective 0 treatment was found to be the application of palladium metal and rr,ag;.es:um nitrate to'tobacco blends. This treatment reduced the incidence of tumors on mouse skin by as much as 95% and the inci- der,ce of mouse skin cancers by as much as 1009. This plot of tumor incidence vs. time (slide 23) illustrates the effect of the treatment. The upper line is the control and - the lower line is the sample treated with palladium and magnesium nitrate. :,dditional moLse skin painting tests have further established the efficacy of the palladium treatment and have demonstrated its applicability to a rather wide range of blend comaositions. Cigarette smoke contains,a number of promoters which act in concert with other true carcinogens to enhance the production of mouse skin tumors. The palladium treatment also significaritly re- duces the cigarette smoke promoting activity. The presence of the nitrate in the tobacco places certain lir,.itations on the finished cigarette. The major combustion p_o- COPY l.y IR HN 01B~'°"t` ~

duct associated the nitrate is nitric oxide. Whi1e there is no direct evidence that this component is harmful at the levels present in smoke, there is a body of opinion that questions whether it may be detrimental to the smoker. With this in mind,•Ligcett has ar5itrari:y set a nitric oxide upper limit equivalent to that present in the top ten best selling U.S. brands. Two general techniques are available to control the levels of nitric oxide in smoke: (1) air dilution and (2) selective filtra- tion. F.lte:native products have been manufactured with tar yields of 8 mg for the cigarettes utilizing air dilution and.10 mg for the samples utilizing selective filtration coupled with modest air dilutior.. An 8 mg cellulose acetate-menthol version has also been prepared. while there can be no argument that the use of the additives has resulted in a product with lower carcinogenic effects, it was necessary to prove that the additives do not introduce any hazard to the smoker. To this end, Liggett has obtained extensive biolo- gical and chemical evidence demonstrating that the presence of the additives will not be detrimental to the smoker. The chemical evidence is based on measurements of specific smoke compounds deemed "undesirable" by health•authorities. The "undesirab:e" compounds in the smoke from the treated filter ciga- rettes are reduced relative to those from conventional filter brands. In addition, no new semi-volatile compounds have been detegted in the smoke from the treated cigarettes. The biological evidence-is based or. a number of experiments. Cytotox:city tests measuring the effcct of cigarette smoke on COPY 1...+' i' S''4 [ i i i S~A 2.(_,~ 243

c-,:I-ured cells, and ciliatoxicity tests measuring the e:fecT of s-oke on chicken trachea demonstrated much lower inhibitory effects produced by smoke from the treated filter cigarettes than from conventional filter cigarettes. Inhalation tests, in which rats were exposed to maximal cora- centrat:Lons of smo;ce,have also been performed. In a six-week test, no evidence of increased toxicity to the animals receiving smoke frc-, palladium-treated cigrsettes was observed relative to un- treated cigarettes. ti~ extended inhalation test, currently in progress, has been evalaated after 5 months of exF.osure. The catalyst treateC ciga-~ ze:tes have shown less pathologic ef:ect thzn the low used as a control. No palladium was found in any of the major oi•ga_s or in the carcass after either 15 or 22 weeks of exposure, using the most sensitive analytical technique available. This chronic inha- l?tion test is scheduled to continue into 1980. 7he results of' the 12 month sacrifice will be available in late 1579, and are expected to parallel the 5-month results. The hasic U.S. pattnt was issued in October of 1977, and several supportive patents are currently being processed. Foreign patent applications have been filed a.nd the pate.nts have issued in several countries. In suarvaary, L&M has developed a method of treating tobacco which neutralizes cigarette tar. Cigarettes have been proc3uczd in a tar :anoe of B-12 ma which are believed to be of commercial c%;ality and which do not demonstrate any new or increasEd hazard when evaluated by extensive chemical and biological tests. COPY V \91 "Y H141 `..I` f...'Y.aF'244