EURL ECVAM in vitro hepatocyte clearance and blood plasma protein binding dataset for 77 chemicals

The European Commission’s Joint Research Centre (JRC) runs the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) which promotes regulatory acceptance of non-animal tests relevant to chemicals safety evaluation, through research, development and validation. In particular, EURL ECVAM engages with numerous international stakeholders to improve approaches to risk assessment, including the generation, sharing and use of non-animal data. Although not typically a regulatory requirement, information about the toxico-kinetics (TK) or biological fate of a substance, characterised by physiological processes of adsorption, distribution, metabolism and excretion (ADME), can be very valuable for predicting toxicological hazard and informing risk assessment. The ADME/TK profiling of chemicals using non-animal methods has advanced considerably in recent years to support prioritisation and screening, read-across, and potentially ab initio safety assessment. The aim of this study was to generate in vitro data on blood-plasma protein binding (relevant to adsorption) and liver hepatocyte clearance (relevant to metabolism) for a set of 77 (primarily) industrial chemicals and to use the data for TK profiling and quantitative in vitro to in vivo extrapolation (qIVIVE). The data have been exploited for a ‘next generation chemical risk assessment’ case study being developed within the context of an international cooperation between regulatory agencies and regulatory science organisations committed to Accelerating the Pace of Chemical Risk Assessment (APCRA).