Evaluation of the biological activity of cigarette‐smoke condensate fractions using sixin vitroshort‐term tests

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Abstract
The biological activity of the volatile part of the particulate phase of cigarette-smoke condensate, the semivolatile fraction, was examined, since the constituents of this material were accessible to selective filtration. Such a process offered a possibility to reduce the biological activity of total cigarette smoke without appreciably affecting the taste. Cigarette-smoke condensate, obtained from domestic American blend type cigarettes, was separated into a nonvolatile and a semivolatile fraction, and the latter was fractionated by liquid-liquid extractions into 4 subfractions: acids, phenols, bases and neutrals. The biological activity of these fractions was investigated using 6 in vitro short-term tests, of which 2, the Ames test and the induction of sister chromatid exchanges, provided information on their genotoxicity, and the other 4 provided information on their cytotoxicity by measuring inhibition of cell growth, inhibition of oxidative metabolism, membrane damage and ciliotoxicity. Sister chromatid exchanges were induced by the total condensate, the nonvolatile and the semivolatile fractions and the subfractions derived from the semivolatile fraction, except the bases. The Ames test showed that the total condensate and the nonvolatile fraction contained direct-acting base-pair mutagens and indirect-acting frameshift mutagens. While the semivolatile fraction was nonmutagenic, 2 of its subfractions, acids and phenols, contained base-pair mutagens, which did not require metabolic activation. The total condensate and the nonvolatile and semivolatile fractions showed similar activity in the 4 cytotoxicity tests. Of the semivolatile subfractions, the acids and the phenols exhibited the highest activity and the bases the lowest; the toxicity observed for the neutrals varied with the test system used.