Steven Stellman - Incremental lifetime cancer risks computed for benzo[a]pyrene and two tobacco-specific N-nitrosamines in mainstream cigarette smoke compared with lung cancer risks derived from epidemiologic data

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      Watanabe, K. H., Djordjevic, M. V., Stellman, S. D., Toccalino,   P. L., Austin, D. F., Pankow, J. F. 55 (2) 123-33-

      Abstract: The manner in which humans smoke   cigarettes is an important determinant of smoking risks. Of the   few investigators that have predicted cancer risks from smoking   on a chemical-specific basis, most used mainstream cigarette   smoke (MCS) carcinogen emissions obtained via machine smoking   protocols that only approximate human smoking conditions. Here we   use data of Djordjevic et al. [Djordjevic, M.V., Stellman, S.D.,   Zang, E., 2000. Doses of nicotine and lung carcinogens delivered   to cigarette smokers. J. Natl. Cancer Inst. 92, 106-111] for MCS   emissions of three carcinogens measured under human smoking   conditions to compute probability distributions of incremental   lifetime cancer risk (ILCR) values using Monte Carlo simulations.   The three carcinogens considered are benzo[a]pyrene,   N'-nitrosonornicotine (NNN), and   4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Computed   NNK ILCR values were compared with lifetime risks of lung cancer   (ILCR(CMD)(obsSigma-lung)) derived from American Cancer Society   Cancer Prevention Studies (CPS) I and II. Within the Monte Carlo   simulation results, NNK was responsible for the greatest ILCR   values for all cancer endpoints: median ILCR values for NNK were   approximately 18-fold and 120-fold higher than medians for NNN   and benzo[a]pyrene, respectively. For "regular" cigarettes, the   NNK median ILCR for lung cancer was lower than   ILCR(CMD)(obsSigma-lung) from CPS-I and II by >90-fold for men   and >4-fold for women. Given what is known about chemical   carcinogens in MCS, this study shows that there is a higher   incidence of lung cancer from exposure to MCS than can be   predicted with current risk assessment methods using available   toxicity and emission data.

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