HORMESIS AS A BIOLOGICAL HYPOTHESIS

A comprehensive effort was undertaken to identify articles demonstrati ng chemical hormesis. Nearly 4000 potentially relevant articles were r etrieved from preliminary computer database searches by using various key word descriptors and extensive cross-referencing. A priori evaluat ion criteria were established including study design features (e.g., n umber of doses, dose range), statistical analysis, and reproducibility of results. Evidence of chemical hormesis was judged to have occurred in approximately 350 of the 4000 studies evaluated. Chemical hormesis was observed in a wide range of taxonomic groups and involved agents representing highly diverse chemical classes, many of potential enviro nmental relevance. Numerous biological end points were assessed; growt h responses were the most prevalent, followed by metabolic effects, lo ngevity, reproductive responses, and survival. Hermetic responses were generally observed to be of limited magnitude. The average low-dose m aximum stimulation was approximately 50% greater than controls. The he rmetic dose-response range was generally limited to about one order of magnitude, with the upper end of the hermetic curve approaching the e stimated no observable effect level for the particular end point. Base d on the evaluation criteria, high to moderate evidence of hormesis wa s observed in studies comprised of > 6 doses; with > 3 doses in the ho rmetic zone. The present analysis suggests that chemical hormesis is a reproducible and relatively common biological phenomenon. A quantitat ive scheme is presented for future application to the database.