A biology-based dynamic approach for the modelling of toxicity in cell-based assays. Part I: Fate modelling

There is a need to integrate existing in vitro dose-response data in a coherent framework for extending their domain of applicability as well as their extrapolation potential. This integration would contribute towards the reduction of animal use in toxicology by using in vitro data for quantitative risk assessment; moreover it would reduce costs and time especially when such approaches would be used for dealing with complex human health and ecotoxicological endpoints. In this work, based on HTS (High Throughput Screening) in vitro data, we have assessed the advantages that a dynamic biology- toxicant fate coupled model for in vitro cell-based assays could provide when assessing toxicity data, in particular, the possibility to obtain the dissolved (free) concentration which can help in raking the toxicity potency of a chemical and improve data reconciliation from several sources taking into account the inherent variability of cell-based assays. The results show that this approach may open a new way of analyzing this type of data sets and of extrapolating the values obtained to calculate in vivo human toxicology thresholds.