Support of In Silico Modeling to Refine In Vitro Systems experiments: example of Zebrafish embryos

• In vitro systems are indispensable tools in safety assessment research, allowing the investigation of adverse pathways under controlled laboratory conditions, thus contributing to our understanding of toxic processes. However, despite their invaluable contributions, traditional in vitro systems often fail to represent the intricate dynamics and physiological complexity of living organisms. 

• In this context, the zebrafish embryo (ZFE) model could address some points regarding physiology and development. Therefore, this model is increasingly used as a screening tool to assess the toxicity or the developmental adverse effects of chemicals. However, the actual exposure is poorly accessible, while a predictive toxicokinetic model based on the physiology (PBTK) could estimate these concentrations.

• Ineris has developed a PBTK model including the main physiological changes in the ZFE such as, the organ ontogenesis, the chorionic transport barrier and its permeabilization, hatching dynamics within a ZFE population over development, and active mediated transport and metabolism mechanisms.