Hormesis: A highly generalizable and reproducible phenomenon with important implications for risk assessment

From a comprehensive search of the literature, the hormesis phenomenon was found to occur over a wide range of chemicals, taxonomic groups, and endpoi nts. By use of computer searches and extensive cross-referencing, nearly 30 00 potentially relevant articles were identified. Evidence of chemical and radiation hormesis was judged to have occurred in approximately 1000 of the se by use of a priori criteria. These criteria included study design featur es (e.g., number of doses, dose range), dose-response relationship, statist ical analysis, and reproducibility of results. Numerous biological endpoint s were assessed, with growth responses the most prevalent, followed by meta bolic effects, reproductive responses, longevity, and cancer. Hermetic resp onses were generally observed to be of limited magnitude with an average ma ximum stimulation of 30 to 60 percent over that of the controls. This maxim um usually occurred 4- to 5-fold below the NOAEL for a particular endpoint. The present analysis suggests that hormesis is a reproducible and generali zable biological phenomenon and is a fundamental component of many, if not most, dose-response relationships. The relatively infrequent observation of hormesis in the literature is believed to be due primarily to experimental design considerations, especially with respect to the number and range of doses and endpoint selection. Because of regulatory considerations, most to xicologic studies have been carried out at high doses above the low-dose re gion where the hormesis phenomenon occurs.