Carcinogenic risk assessment of complex mixtures

Although procedures for assessing the carcinogenic risks associated with exposure to individual chemicals are relatively well developed, risk assessment methods for mixtures of chemicals are still in the developmental stage. In this paper, we examine the difficulties in assessing the risks of exposure to complex mixtures, with special reference to the potential for synergistic effects among the components of the mixture. Statistical models for describing the joint action of multiple exposures are reviewed, and their implications for low-dose risk assessment are examined. The potential use of pharmacokinetic models to describe the metabolism of mixtures is also considered. Application of these results in regulating mixtures of carcinogenic substances is illustrated using examples involving multiple contaminants in drinking water and polycyclic aromatic hydrocarbons produced from combustion sources.