SaferWorldbyDesign: QIVIVE as a central piece in NGRA: assessment of DNT in the ONTOX project
Understanding the absorption, distribution, metabolism, and excretion (ADME) of a chemical is fundamental to predicting its toxicity. Physiologically-based kinetic (PBK) models simulate these ADME processes by integrating physiological and chemical-specific data, making them crucial tools for next-generation risk assessment. Specifically, they enable the extrapolation of in vitro effect concentrations to in vivo bioequivalent doses, a process known as quantitative in vitro-in vivo extrapolation (QIVIVE). However, accurate QIVIVE also requires assessing chemical availability within the in vitro system. This can be achieved using in silico models that consider both chemical properties and system characteristics, paralleling the approach of PBK modeling. This presentation will explain the QIVIVE framework and specific case-studies from the ONTOX project, focusing on developmental neurotoxicity (DNT). Here, the physiology of pregnant women, characteristics of DNT in vitro systems, and DNT chemical space needed to be considered, which illustrated the benefit of developing tools and designing their integration in an ontological manner. Open-source tools, including the Open Systems Pharmacology suite and R, were used to develop the presented QIVIVE case-studies.
Speaker: Susana Proenca (ESQLabs)
Susana is a scientist in esqLABS GmbH since October 2024. She started her studies in biology and gradually entered the toxicokinetic field, first with a traineeship in ECVAM-JRC and then with her PhD in the Institute for Risk Assessment, Utrecht University, where she focused on kinetics in different in vitro systems. Afterwards, Susana worked as a post-doc researcher in Wageningen University in the ambit of the ONTOX project, looking again at the in vitro kinetics. Since then, Susana has kept working in the ONTOX project but now focused on developing PBK models and QIVIVE frameworks integrating different in silico models and in vitro data.
