In the mid-1980s, each major US cigarette manufacturer prepared a list of those ingredients added at that time to its cigarette products. The lists were combined into one and submitted to the US Office of Smoking and Health in 1986. It comprised 599 entities. On the basis of extensive literature survey and examination of much unpublished data from the Tobacco Industry members on the chemistry and toxicology of the ingredients, a panel of eminent toxicologists assessed the safety of each listed ingredient with regard to its pyrolysate components and its possible effect when added to cigarette tobacco on the chemical and biological properties of the cigarette mainstream smoke. Subsequently, Doull et al. listed the 599 ingredients and summarized the conclusions of the panel on their effect on the chemical and biological properties of cigarette smoke.
In addition to the panel and Doull et al., other investigators have noted that many of the compounds used as ingredients in cigarette tobacco blends are identical with or similar to identified components of tobacco and/or tobacco smoke. The validity of this statement is obvious when the compounds in the Doull et al. list are cataloged as in Table 1. Those tobacco ingredients that are not individual compounds but are naturally-occurring oils, resins, etc. or extracts of naturally-occurring materials not only contain many of the compounds listed by Doull et al. as tobacco additives but also contain many of the same compounds present in tobacco.
Detailed examination of the literature on the chemical and biological properties of the recently used tobacco ingredients listed by Doull et al. plus a massive amount of chemical and biological data generated during the past several decades indicates that not only does none of the Doull et al. listed ingredients contribute any significant adverse chemical properties to cigarette mainstream smoke (MSS) but also none affects adversely the biological properties of the MSS.
The chemical factors examined included: a) The effect on MSS composition of the ingredients added to cigarette tobacco at the usual use level or several times that. In two major series of studies, one by Carmines et al. and one by Baker et al., the effect of the added ingredient on the concentration in mainstream smoke of specific components defined as toxicants was determined. The Carmines et al. study involved analysis of the smoke components suggested by the US Consumer Product Safety Commission and of concern to the International Agency for Research on Cancer (IARC). The Baker et al. study involved analysis of the so-called ‘Hoffmann analytes’ in cigarette smoke. b) The nature of the pyrolysis products generated during the smoking process or during pyrolysis of an individual ingredient under conditions approximating those in the cigarette pyrolysis zone. In many instances when the added ingredient is a compound, a significant percentage of it is transferred unchanged to the MSS and sidestream smoke (SSS). The small percentage not transferred intact to the smoke is seldom converted to an MSS component possessing significant toxic properties.
The extensive biological studies that showed no significant adverse effect of the MSS from ingredient-containing cigarettes included: a) The specific tumorigenicity to laboratory animal skin of the mainstream cigarette smoke condensate (CSC) from ingredient-containing cigarettes vs. the mainstream CSC from ingredient-free cigarettes. b) Exposure of laboratory animals via inhalation to the MSS from ingredient-containing cigarettes vs. the MSS from ingredient-free cigarettes. c) Determination in a variety of tests of the in vitro genotoxicity of the mainstream particulate phase and/or vapor phase.
In addition, the results of non-tobacco-related studies are available in which many individual compounds on the Doull et al. list were assayed for mutagenicity in the Ames test with several strains of Salmonella typhimurium. An excellent example is the 1984 study by Ishidate et al. who examined the mutagenicity of many compounds included as additives in Japanese foods. Over 40 of the compounds exhibiting non-mutagenicity also occur on the Doull et al. tobacco ingredient list.
Assessment of the total chemical and biological data cited herein provides a noteworthy contradiction to the much repeated assertions - with no data supporting them - that the ingredients added to cigarette tobacco result in significant adverse changes in the chemical and biological properties of the cigarette MSS.