Biotransformation in vitro: An essential consideration in the quantitative in vitro-to-in vivo extrapolation (QIVIVE) of toxicity data.

Early consideration of the multiplicity of factors that govern the biological fate of foreign compounds in living systems is a necessary prerequisite for the quantitative in vitro-in vivo extrapolation (QIVIVE) of toxicity data. Substantial technological advances in in vitro methodologies have facilitated the study of in vitro metabolism and the further use of such data for in vivo prediction. However, extrapolation to in vivo with a comfortable degree of confidence, requires continuous progress in the field to address challenges such as e.g., in vitro evaluation of chemical-chemical interactions, accounting for individual variability but also analytical challenges for ensuring sensitive measurement technologies. This paper discusses the current status of in vitro metabolism studies for QIVIVE extrapolation, serving today's hazard and risk assessment needs. A short overview of the methodologies for in vitro metabolism studies is given. Furthermore, recommendations for priority research and other activities are provided to ensure further widespread uptake of in vitro metabolism methods in 21st century toxicology. The need for more streamlined and explicitly described integrated approaches to reflect the physiology and the related dynamic and kinetic processes of the human body is highlighted i.e., using in vitro data in combination with in silico approaches.