Carcinogenic Mixtures

Human populations are generally exposed simultaneously to a number of toxicants present in the environment, including complex mixtures of unknown and variable origin. While scientific methods for evaluating the potential carcinogenic risks of pure compounds are relatively well established, methods for assessing the risks of complex mixtures are somewhat less developed. This article provides a report of a recent workshop on carcinogenic mixtures sponsored by the Committee on Toxicology of the U.S. National Research Council, in which toxicological, epidemiological, and statistical approaches to carcinogenic risk assessment for mixtures were discussed. Complex mixtures, such as diesel emissions and tobacco smoke, have been shown to have carcinogenic potential. Bioassay‐directed fractionation based on short‐term screening tests for genotoxicity has also been used in identifying carcinogenic components of mixtures. Both toxicological and epidemiological studies have identified clear interactions between chemical carcinogens, including synergistic effects at moderate to high doses. To date, laboratory studies have demonstrated over 900 interactions involving nearly 200 chemical carcinogens. At lower doses, theoretical arguments suggest that risks may be near additive. Thus, additivity at low doses has been invoked as a working hypothesis by regulatory authorities in the absence of evidence to the contrary. Future studies of the joint effects of carcinogenic agents may serve to elucidate the mechanisms by which interactions occur at higher doses.