Effect-directed analysis and beyond: how to find causal environmental toxicants

Humans and wildlife are exposed to complex environmental mixtures. Identifying causal toxic pollutants in environmental samples remains challenging because of the high complexity of sample mixtures and the unknown nature of the potential toxicants. In the field of environmental chemistry and toxicology, this pursuit of causal toxicants leads us to the method of effect-directed analysis (EDA), an integrated method comprised of three iterative modules: (1) bioassays to guide component prioritization; (2) fractionation to reduce the mixture complexity; and (3) chemical analysis to identify the toxicants. In this commentary review, we try to provide a concise guideline for EDA beginners by summarizing good practices from successful EDA studies, categorized by sample-toxicity pair selection, efficient separation, and chemical analysis. We also discussed the practical challenges faced with current EDA practices. Based on these above, we try to provide suggestions and perspectives for future EDA studies. Specifically, we discussed the potential of applying EDA on human biological examples to identify the environmental causes of human diseases. We proposed future collaboration between environmental chemists and toxicologists, environmental health scientists, epidemiologists, physicians, and social scientists.