title: The in vitro cytotoxicity and genotoxicity of cigarette smoke particulate matter with reduced toxicant yields.
abstract: Tobacco smoke contains more than 5600 constituents, of which approximately 150 are toxicants. This paper describes the activities in the Neutral Red uptake (NRU) assay, the Salmonella mutagenicity test (SAL), the mouse lymphoma mammalian cell mutation assay (MLA) and the in vitro micronucleus test (IVMNT) of Particulate Matter (PM) obtained from experimental cigarettes (ECs), designed to produce reduced levels of toxicants. The designs included tobacco substitute sheet (TSS) containing glycerol, which dilutes toxicants in smoke, or the incorporation of blend-treated (BT) tobacco to reduce the levels of nitrogenous toxicant precursors and some polyphenols. All samples were cytotoxic in the NRU, however TSS reduced PM cytotoxicity in this assay. All PMs were mutagenic in the SAL, MLA and IVMNT. Reductions in bacterial mutagenicity were observed in the SAL, for cigarettes with BT tobacco, compared with their respective controls. The quantitative changes in bacterial mutagenicity could be explained by analytical chemistry data on smoke generated from the ECs used in the study. These observations, and the absence of consistent qualitative differences in the activities of the experimental, control and reference cigarettes, suggest that reduced toxicity cigarettes, as measured by the tests described in this paper, may be developed without introducing any additional cytotoxic or genotoxic hazards, but the impact of this on human health risks remains unknown.
authors.affiliation: British American Tobacco, Group Research and Development, Regents Park Road, Southampton SO15 8TL, UK. robert.d.combes@gmail.com
authors.forename: R
authors.initials: R
authors.lastname: Combes
authors.forename: K
authors.initials: K
authors.lastname: Scott
authors.forename: I
authors.initials: I
authors.lastname: Crooks
authors.forename: D
authors.initials: D
authors.lastname: Dillon
authors.forename: C
authors.initials: C
authors.lastname: Meredith
authors.forename: K
authors.initials: K
authors.lastname: McAdam
authors.forename: C
authors.initials: C
authors.lastname: Proctor
mesh_terms: D000818:Animals; D001681:Biological Assay; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009499:Neutral Red / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D009153:Mutagens; D014028:Tobacco Smoke Pollution; D009499:Neutral Red