Chair: Richard A. Becker, PhD, DABT, American Chemistry Council, Washington, DC
Co-Chair: Lisa M. Sweeney, PhD, DABT, Naval Medical Research Unit Dayton, Dayton, OH
 

Overview

The development and use of in vitro methods to examine potential effects of consumer product chemicals, commodity substances, food additives and ingredients is accelerating. Compared to traditional animal toxicity studies, advanced high throughput screening methods (HTS) and high content cellular based omics hold considerable promise to more efficiently define biological activity profiles of chemicals. However, methods are needed to extrapolate the concentrations found to elicit effects in vitro to equivalent doses and relevance in humans. This is accomplished with In Vitro to In Vivo Extrapolation (IVIVE), a technique that uses knowledge (or measurements) of chemical specific distribution parameters and physiologically-based pharmacokinetic modeling to calculate oral equivalent doses (or internal circulating/target organ concentrations) in humans. Such IVIVE-derived doses can then be compared to modeled or measured human intakes or exposures to better understand margins of exposure.
 

The colloquium started with an overview of IVIVE and a discussion of the principles underpinning the development of the methodology and highlight key elements to think through when considering applying IVIVE. Second, technical details and data needed for IVIVE were discussed. Third, examples of IVIVE applications in chemical assessment (including substances relevant to food safety) were presented. Fourth, the opportunities and challenges for using IVIVE in safety evaluations were discussed. Finally, the colloquium concluded with a panel discussion addressing the key issues brought up by the speakers and questions from participants.