A New In Vitro Toxicology: Shifting from Cells to Serum by Exploiting Pathology Data and Machine Learning to Investigate Liver Toxicity

In vitro toxicology is traditionally cell-based systems of 2D or 3D cultures on which chemical and drug toxicity can be tested in advance of human application, and without resort to animal testing. This White Paper proposes another in vitro toxicology based on serum/plasma analyses, specifically those available through routine and special diagnostic pathology. The combination of diagnostic automation, the central role of the laboratory in modern healthcare, and sophisticated computational tools allows high-dimensional data modeling and prediction of total tissue and organ responses to toxic insults in vivo. To illustrate this concept, the liver function test is examined, with reference to general toxicity as detected by gamma-glutamyl transferase. This new in vitro toxicology is valuable in isolation, but will become more powerful when integrated with cell-based toxicology, including organ-on-a-chip technologies.