Component-based risk assessment approaches with additivity and interactions

Abstract

Mixture risk assessments are most often based on toxicology information for the component chemicals, primarily because dose-response information on the mixture of concern is inadequate. The most widely used component methods in mixture risk assessment are based on dose addition or response addition. Two methods described here are derived from dose addition: the hazard index and the relative potency factor method. The hazard index informs safety decisions for specific environmental exposures, while the relative potency factor formula actually estimates the health risk for specific environmental exposures. Use of dose addition is supported when chemicals are toxicologically similar (see Chap. 9). The hazard index is motivated by dose addition and is applied to chemicals having a common toxicological target organ, which is fairly weak evidence of toxicological similarity. A weight of evidence system for binary mixtures allows the hazard index to be modified to incorporate toxicological interactions. Relative potency factors are applied in a dose addition formula and are developed for chemicals that have good evidence of toxicological similarity, e.g., chemicals that share a common adverse outcome pathway (AOP) and are assumed not to elicit toxicological interactions. Two other methods described here are related to response addition, both requiring the assumption of toxicological independence (see Chap. 9). When response is a risk (probability), response addition follows the statistical formula for independent events. When response is a measured effect, the addition is called effect summation, where the component incremental effects are added. This chapter reviews the history and concepts related to component-based methods for health risk assessment of chemical mixtures, illustrates commonly used methods and some modifications, and discusses strengths, limitations, and likely future development.