Abstract
Accurate risk assessments for chemical health hazards are closely tied to the ability to predict the conditions under which toxic effects are likely to occur in exposed people based on observations of toxicity in experimental animals. These predictions require (1) knowledge of the dose-response characteristics for the effect and (2) the ability, based on mechanistic considerations, to extrapolate to expected incidences at much lower doses in exposed people. An important concept for these extrapolations is the definition of “dose,” that is, to what measure of “dose” should we relate toxicity and how does the chosen measure of dose extrapolate across species? This brief commentary looks at the evolution of our understanding of both the chemical and biological aspects of the concept of tissue dose