Mike Santillo of the FDA

"Predicting toxicity from a chemistry perspective using in vitro and in silico methods"

Animal testing has been traditionally used to predict human health hazards of chemicals. However, animal testing is not sustainable due to vast numbers of chemicals that require testing along with being inefficient, laborious, expensive, and often unpredictive of human toxicity. Therefore, to address this challenge, alternative methods are being developed, featuring measurements in cells (in vitro models) or predictions based upon chemical structures (in silico models). Toxic effects often originate from interactions between chemicals and biological targets within cells (e.g., enzymes, transporters, receptors, and ion channels). Using in vitro and in silico methods, these chemical-target interactions can be identified, which provide important information to understand their potential toxicity. In this seminar, two projects involving biological targets will be presented. In the first project, an in vitro assay was used to identify inhibitors of acetylcholinesterase, a biological target associated with toxicity, among a library of 10,000 chemicals relevant to human health. In the second project, in silico methods were used to predict interactions between a group of chemicals and 4,000 biological targets; this may aid in understanding toxicity of these chemicals since they have not been previously studied in humans. Together, these in vitro and in silico methods can help identify emerging chemical hazards, prioritize subsequent testing, and provide data that can help predict toxicity.