An international effort to promote the regulatory use of PBK models based on non-animal data

Abstract

Abstract The Organisation for Economic Co-operation and Development (OECD) coordinates international efforts to promote the regulatory use of Physiologically Based Kinetic (PBK) models based on non-animal data. The new generation PBK models rely on in vitro and in silico ADME (Absorption, Distribution, Metabolism and Excretion) data and aim to provide internal dose metrics that are considered more predictive when establishing biological responses that are needed in chemical risk assessment. However, the uncertainty derived from the chemical-dependent parameters (physicochemical and ADME properties) of PBK models for chemicals with no in vivo data need to be clearly communicated to the regulators evaluating data derived from these tools. This manuscript highlights these international efforts that aim to enhance regulatory acceptance of new generation PBK models through the development of a harmonised approach for characterising, validating and reporting them.