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Stephen S Ferguson

OpenTox Virtual Conference 2023

Modeling human hepatic metabolism and toxicity using NAMs:  How much is enough?

Prediction of human responses to chemical exposures is a fundamental challenge for pharmaceutical and environmental toxicology research. Xenobiotic metabolism continues to arise as central role in toxicity mechanisms and our understanding of human internal exposures. At the Division of Translational Toxicology (DTT) within the National Institute of Environmental Health Sciences (NIEHS), we have been addressing these challenges through various Tox21 efforts to develop and qualify novel approaches to emulate human hepatic metabolism and corresponding hepatocellular responses (e.g., toxicity) to xenobiotic exposures with physiologically-relevant in vitro liver models. Pairing highly differentiated hepatocellular systems with high dimensional assay platforms (e.g., high throughput transcriptomics, metabolomics, cellular imaging) has enabled broader use of new approach methods (NAMs) to address real-world challenges. In this presentation, I will outline progress towards building confidence with these emerging tools for decision-making (e.g., prioritization, safer alternatives).