Human-based Systems in Drug and Chemical Safety Testing — toward Replacement,the ‘Single R’

Abstract

The Three Rs was a concept originally conceived as a means of reducing the suffering of laboratory animals that are used largely in identifying any potential safety issues with chemicals to which humans may be exposed. However, with growing evidence of the shortcomings of laboratory animal testing to reliably predict human responsiveness to such chemicals, questions are now being asked as to whether it is appropriate to use animals as human surrogates at all. This raises the question of whether, of the original Three Rs, two — Reduction and Refinement — are potentially redundant, and whether, instead, we should concentrate on the third R: Replacement. And if this is the best way forward, it is inevitable that this R should be based firmly on human biology. The present review outlines the current state-of-the-art regarding our access to human biology through in vitro, in silico and in vivo technologies, identifying strengths, weaknesses and opportunities, and goes on to address the prospect of achieving a single R, with some suggestions as to how to progress toward this goal.