Development of an in vitro metabolic hepatic clearance method

There is increasing demand from in vitro method developers, validation bodies, in vitro method end-users as well as receiving authorities and OECD to integrate kinetics information in toxicity testing in order to improve chemical risk assessment. A strategic way to do this is detailed in the "EURL ECVAM strategy for achieving 3Rs impact in the assessment of toxicokinetics and systemic toxicity" (Bessems J et al. 2015). One of the strategic aims of this report urges for the development and applied use of in vitro kinetic methods for absorption, distribution, metabolism and excretion to be used in the future risk assessment approaches using new advanced methodologies (NAMs). Information on metabolism has been identified as a critical piece of information in integrated test strategies based on non-animal methods. Therefore, the purpose of this report is to describe the preliminary experimental work towards a representative in vitro human hepatic metabolic clearance method that can be ultimately used in future defined approaches for toxicological risk assessment