Chairs: Abdulkarim Najjar & Bambou Tan
Physiologically Based Pharmacokinetics (PBPK) models have been broadly proposed and investigated as a New Approach Methodology (NAM) and key to establish Next generation risk assessment (NGRA). PBPK is implemented either to predict internal concentrations after exposure to ingredients, within the cosmetics industry – or for in vitro to in vivo extrapolation (IVIVE) of the in vitro point of departure to enable animal-free risk assessment. Regulatory guidance has been published to guide the development of top-down PBPK modelling. The bottom-up approach for PBPK of data poor chemicals, has been discussed in the OECD Guidance 331. Nonetheless, while OECD Guidance 331 provides a framework, it acknowledges the challenge of validating models built solely on in vitro and in silico data. Rigorous Absorption, Distribution, Metabolism, and Elimination (ADME) characterisation through the study of in vitro properties have a crucial role in increasing confidence in those tools. This is complementary to the approaches that are proposed by OECD guidance 331 for characterisation of the uncertainty, sensitivity analysis, and assessment of the underlying biological assumptions and equations. These aspects will be covered in this session, discussing the assumptions to be made to be protective, and their use for risk assessment in the NGRA context. A number of case studies will be presented in this session, in which a rigorous in vitro ADME characterisation has improved the overall performance of the PBPK model and allowed integrating a robust quantification of uncertainty in the model’s outcome.
Speakers
- Ans Punt – Best practices in Physiologically Based Kinetic (PBK) modelling for Next Generation Risk Assessment (NGRA)
- Nazanin Golbamaki – STRATEGIC IN VITRO TESTING FOR PARAMETERIZATION IN PBK MODEL DEVELOPMENT OF COSMETIC INGREDIENTS
- Jeremy Perrier – CHALLENGES AND PERSPECTIVES FOR REGULATORY ACCEPTANCE OF BOTTOM UP NGRA PBK MODELS
- Nynke Kramer – Quantitative In Vitro In Vivo Extrapolation of Nephrotoxicants using PBPK Modelling
- Daniela Lange – Evaluation of In Vitro Methods to Investigate Long-Term Hepatic Clearance Using Three Low-Clearance Compounds