Evaluating chemical interaction studies for mixture risk assessment

We describe a set of criteria to evaluate the quality of data and interpret ations in chemical interaction studies. These criteria reflect the consensu s of the literature on interaction analysis developed over decades of resea rch in pharmacology, toxicology, and biometry; address common pitfalls in p ublished interaction studies; and can be easily applied to common methods o f interaction analysis. The criteria apply broadly to interaction data for drugs, pesticides, industrial chemicals, food additives, and natural produc ts and are intended to assist risk assessors who must evaluate interaction studies for use in component-based mixture risk assessments. The criteria m ay also assist researchers interested in conducting interaction studies to inform mixture risk assessment. The criteria are also intended to serve lar ger scientific goals, including increasing the repeatability of results obt ained in chemical interaction studies, enhancing the reliability of conclus ions drawn from interaction data, providing greater consistency of interpre tations among various analysts, and decreasing uncertainty in using interac tion data in risk assessments. We describe the basis for each criterion and demonstrate their utility by using them to evaluate interaction studies fr om the recent toxicological and pharmacological literature, which serve as examples of different types of data sets that the risk assessor may encount er.