Theoretical and mathematical foundation of the Virtual Cell Based Assay - A review

There is a need to interpret in vitro concentration-viability data in terms of the actual concentration that the cells are exposed to, rather than the nominal concentration applied to the test system. We have developed a process-based model to simulate the kinetics and dynamics of a chemical compound in cell-based in vitro assays. In the present paper we describe the mathematical equations governing this model as well as the parameters that are needed to run the model. The Virtual Cell Based Assay (VCBA) is an integrated model composed of: [1] a fate and transport model; [2] a cell partitioning model; [3] a cell growth and division model; [4] a toxicity and effects model; [5] the experimental set up. The purpose of the VCBA is to simulate the medium and intracellular concentrations, which can be used on its own to design and interpret in vitro experiments, and in combination with physiologically based kinetic (PBK) models to perform in vitro to in vivo extrapolation. The results can be used in chemical risk assessment to link an external dose to an internal effect or vice versa, using solely in vitro and in silico tools and thereby avoiding animal testing.