Exercises in the use of weight-of-evidence approach for chemical-mixture interactions

Consistency and accuracy are two testable characteristics of a proposed weight-of-evidence approach to evaluate chemical interactions (Mumtaz and Durkin, 1992). A study was designed to evaluate the consistency characteristics. Existing interaction data between two pairs of chemicals were evaluated using this approach: (1) polychlorinated biphenyls and carbon tetrachloride, and (2) cadmium and zinc. The results of this study show that this methodology can be consistently applied by a group of scientists with varying experience in risk assessment. The influence on toxicity can be estimated with confidence for certain pairs of chemicals, but not for others. The next step to further the development of this approach is to test its accuracy characteristics and this work is underway. Accuracy characteristics cannot be determined through existing data, bur only through specifically designed experimental studies to discern chemical interactions at low and high concentrations of chemical mixtures and as a function of the individual component ratios.