U-shaped dose-responses in biology, toxicology, and public health

The occurrence of U-shaped dose-response relationships (often termed hormes is) has been documented in numerous biological, toxicological, and pharmaco logical investigations. Many of the endpoints studied are of considerable s ignificance to public health (e.g. body weight, cholesterol levels, ethanol consumption, longevity, cancer incidence, etc). Despite the fact that U-sh aped dose-responses are widely and independently observed, little attempt h as been made to assess this phenomenon in an integrative manner. This revie w provides an overview of the historical foundations of hormesis and a disc ussion of its definition within a mechanistic framework. The occurrence, ge neralizability, and biological significance of U-shaped dose-response relat ionships along with the concept of biological optimality are addressed.