Chapter 7 - Extrapolation of In Vitro Results to Predict Human Toxicity

Abstract

A gold standard for toxicity prediction in a living system is very much needed by the toxicology community. The enormous effort that gets unaccounted for between the numbers of successful drugs reaching the market and the investment during drug discovery needs to be addressed for better success. Classical methods are not sufficient enough anymore to predict the toxicity as a whole by taking into account the species specificity, drug metabolism, drug exposure, acute versus chronic effect, and existing ailment multiple effects occurring at the same time. Routine biochemical measurements typically include enzyme activity and metabolite concentration measurement in a cell-free environment. Observations gathered from one type of in vitro system remotely mimic the whole animal behavior. Moreover, these biochemical measurements are typically the end point of toxicity when the derangement in the biological processes causes terminal damage to the system. Onset as well as progress of toxicity can hardly be accounted for from these “end point”–type observations. A better predictive method need to be able to integrate various forms of alteration measured in multiple cell system under different condition—a steady accumulation of changes eventually culminates into an irreversible outcome. An endeavor to collate various results obtained from different in vitro systems on different measurements together may reveal the holistic picture behind toxicity.