Evaluating Chemical Interaction Studies for Mixture Risk Assessment

We describe a set of criteria to evaluate the quality of data and interpretations in chemical interaction studies. These criteria reflect the consensus of the literature on interaction analysis developed over decades of research in pharmacology, toxicology, and biometry; address common pitfalls in published interaction studies; and can be easily applied to common methods of interaction analysis. The criteria apply broadly to interaction data for drugs, pesticides, industrial chemicals, food additives, and natural products and are intended to assist risk assessors who must evaluate interaction studies for use in component-based mixture risk assessments. The criteria may also assist researchers interested in conducting interaction studies to inform mixture risk assessment. The criteria are also intended to serve larger scientific goals, including increasing the repeatability of results obtained in chemical interaction studies, enhancing the reliability of conclusions drawn from interaction data, providing greater consistency of interpretations among various analysts, and decreasing uncertainty in using interaction data in risk assessments. We describe the basis for each criterion and demonstrate their utility by using them to evaluate interaction studies from the recent toxicological and pharmacological literature, which serve as examples of different types of data sets that the risk assessor may encounter.