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Mixture toxicology in the 21st century: Pathway-based concepts and tools
Citation:
Ankley, G. Mixture toxicology in the 21st century: Pathway-based concepts and tools. SETAC Focused Topic Meeting on Mixture Assessment, Denver, CO, September 06 - 08, 2017.
Impact/Purpose:
Assessing the potential risk of chemical mixtures remains a significant challenge both for human health and the environment. However, many new/evolving predictive toxicology tools and concepts, including in silico systems models, high-throughput screening assays and the adverse outcome pathway framework, could be fruitfully brought to bear on this challenge.
Description:
The past decade has witnessed notable evolution of approaches focused on predicting chemical hazards and risks in the absence of empirical data from resource-intensive in vivo toxicity tests. In silico models, in vitro high-throughput toxicity assays, and short-term in vivo tests with pathway-specific molecular and biochemical endpoints provide the mechanistic data to support these predictive approaches. And, the adverse outcome pathway (AOP) framework provides a conceptual basis for translation of the resultant mechanistic knowledge into the types of apical (whole organism) responses needed for risk assessment (e.g., changes in survival, growth and reproduction). To date, these predictive tools and concepts have largely been applied only to prospective assessments of single chemicals. However, the various approaches can be just as useful for assessing effects of contaminant mixtures in both prospective and diagnostic assessments. This presentation will describe the conceptual and technical underpinnings of various tools and approaches used in predictive toxicology, and provide “real world” examples of their application to ecological assessments of the occurrence and effects of chemical mixtures. The views expressed in this presentation are those of the author and do not represent the views or policies of the USEPA.