Translational Toxicology and the Work of the Predictive Safety Testing Consortium

Toxicology has always been translational—at least with respect to its primary focus on human “health.” The earliest “toxicologists” explored the effects of plant and animal poisons on humans, conducting experiments on (often unsuspecting) human subjects.1 Not until the sulfanilamide disaster of 1937, the 1938 US Federal Food, Drug and Cosmetic Act, and the Nuremberg Code did animals become central to the experimental assessment of chemical safety.2,3 Now, with harmonization of requirements among various international regulatory agencies, the types and design of safety evaluation studies conducted to support first-in-human investigations have been reasonably standardized.4 Most drug safety studies are conducted in both a rodent and a nonrodent species, with the aim of identifying adverse reactions relevant to human health, potential target organs of toxicity, a dose for first-in-human studies, a margin of safety between the efficacious and toxic doses, and strategies for monitoring safety during clinical trials.5 Clinical Pharmacology & Therapeutics (2009); 85, 3, 327–330 doi:10.1038/clpt.2008.270