The Composition of Cigarette Smoke: Problems with Lists of Tumorigens

Since the mid-1960s, various investigators, agencies, and institutions have disseminated lists of cigarette mainstream smoke (MSS) components reported to be tumorigenic on the basis of laboratory bioassays conducted under conditions significantly different from those encountered by the smoker during exposure to the components in the cigarette MSS aerosol. Since 1990, numerous lists of cigarette MSS components, defined as significant tumorigens, have been compiled by American Health Foundation personnel, Occupational Safety and Health Administration (OSHA), Fowles and Bates, and R.J. Reynolds R&D personnel. The purpose of most of the reports was to define human risk assessment and to dissuade smokers from smoking. Various investigators and agencies have frequently cited the earlier and/or the more recent lists of tumorigenic entities. The recent compilations, involving nearly 80 MSS components, suffer from serious deficiencies including: a) Use of per cigarette delivery ranges for specified components which often include analytical data from cigarettes manufactured in the 1950s and 1960s which are not comparable to lower-'tar’ yield cigarettes manufactured since the mid-1970s. b) Absence of standard analytical procedures for most of the listed components. c) Methodological considerations regarding bioassays used to determine tumorigenicity of the listed MSS components. d) Difficulty in extrapolating in vivo bioassay data obtained by non-inhalation modes of administration of a single compound to the human smoking situation involving inhalation of a complex aerosol containing that compound. e) Inhalation data inadequacies regarding the tumorigenicity of many of the components. f) Several tobacco smoke components are listed despite the fact their presence has not been confirmed, their MSS level has not been defined, or their MSS level is no longer relevant. g) Insufficient consideration of inhibitors of tumorigenesis and mutagenesis found in MSS. h) Difficulty in extrapolation of inhibition/anticarcinogenesis/antimutagenesis observed in a one-on-one in vivo situation to the complex MSS aerosol situation. j) Alternate exposures to many of the listed smoke components. k) Discrepancies among the lists. l) Discrepancies within the lists.A more appropriate use of the listing process is the identification of potential chemical targets for removal from, or inhibition in cigarette MSS.