The relative toxicity of compounds in mainstream cigarette smoke condensate

Many different in vivo and in vitro tests are currently used to assess the toxicity of chemicals and complex mixtures such as cigarette smoke condensa te. In vivo tests include assays in rodents to determine carcinogenicity, t umorigenicity and reproductive effects. In vitro tests of mutagenicity are conducted with both bacterial and mammalian cell systems. A first step towa rds lowering the toxicity of cigarette smoke condensate is the identificati on of the relevant compounds. However, changing the concentration of a give n smoke component may not linearly alter the biological activity of the com plex mixture due to interactive effects. The "effective toxicity" of a chem ical constituent is a function of the concentration, the metabolic fate, th e potency in in vivo and in vitro assays, and the ability to reach the targ et tissues. The logarithm of the octanol-water partition coefficient (log P ) is an important parameter since it affects metabolism, biological transpo rt properties and intrinsic toxicity. Using concentration data from the Int ernational Agency for Cancer Research (IARC), biological activity data from the Registry of Toxic Effects of Chemical Substances (RTECS) database and measured and calculated log P values, we have rank ordered some of the impo rtant compounds in cigarette smoke condensate by their measured or potentia l toxicity. Condensates from different cigarette brands, tar categories and styles vary in their concentrations of these compounds. Chemicals of great er commercial or scientific interest may be toxicity tested more extensivel y, thereby increasing the probability of positive test results and highligh ting the need for consideration of structure-activity relationships. (C) 20 00 Elsevier Science Ltd. All rights reserved.