In fact, these new cigarettes require flavor corrections by additives in order to be acceptable to the consumer. Wrong assumption Within British American Tobacco, flavor ingredients are not used any more on low tar cigarettes than on higher yield cigarettes - menthol is an exception - its use increases as tar yield decreases STUDIES ON INGREDIENTS SINCE 1950s Pyrolysis Effects on smoke chemistry Mouse skin painting Inhalation toxicity In vitro bioassays - genotoxicity - cytotoxicity PUBLISHED REVIEWS ON TOBACCO INGREDIENTS Paschke, Scherer and Heller, 2002 Rodgman, 2002, two reviews, including much previously unpublished RJRT work Dixon et al., 2000, effects of ammonia ingredients on nicotine transfer andbioavailability RECENT MAJOR STUDIES ON INGREDIENTS Carmines et al., 2002, four papers chemistry and biology Gaworski et al., 1997-2002, four papers biology Baker et al., 2004, four papers pyrolysis, chemistry and biology Paschke, Scherer and Heller 198 papers/patents from 1952-2002 on ingredients reviewed Over 300 ingredients Smoke chemistry 150 single ingredients + 61 combinations Pyrolysis (161 papers) Smoke biological activity (37 papers) Paschke, Scherer and Heller - Conclusions Tobacco ingredients used commercially do not increase the biological activity of cigarette smoke Many gaps in knowledge on pyrolysis and transfer to smoke Standard analytical methods needed for influence of ingredients on smoke chemistry Rodgman Reviews- (1) Flavorings - (2) Casings Includes previously unpublished RJRT studies Includes work aimed at identifying precursors of smoke toxins -predicted that relatively volatile flavors would distil out of cigarette burning zone -studies on ingredients that could potentially generate smoke toxins Rodgman - Conclusions Neither flavorings nor casing and humectant ingredients added to tobacco during commercial cigarette manufacture in the USA increase the toxicity of cigarette smoke Carmines and co-workers, 2002 Study of 333 ingredients added to tobacco in 3 mixtures at normal and 1.5 3 x normal use Effects on 51 Hoffmann analytes in smoke Effects on Ames and neutral red uptake bioassays Effects on sub-chronic inhalation toxicity (90-day rat inhalation) Carmines and co-workers - conclusions The addition of the 333 ingredients had not affected the toxicity of smoke, even in the exaggerated high level mixtures

and/or (3) insecticides acting on nAChRs, as with the subsequently developed neonicotinoids 17
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The deposition values in three experimental rounds (N1, N2 and N3) were noted to be in range of 15% standard deviation validating uniform smoke distribution across different runs (Fig