The Dose Determines the Stimulation (and Poison): Development of A Chemical Hormesis Database

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Abstract
A comprehensive effort was undertaken to identify articles demonstrating chemical hormesis. Nearly 4000 potentially relevant articles were retrieved from preliminary computer searches utilizing various keyword descriptors and extensive cross-referencing. A priori evaluation criteria were established including study design features (e.g., number 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 environmental relevance. Numerous biologic endpoints were assessed, with growth responses the most prevalent, followed by metabolic effects, longevity, reproductive responses, and survival. Hormetic responses were generally observed to be of limited magnitude with the average low-dose maximum stimulation approximately 50% greater than controls. The hormetic dose-response range was generally limited to about one order of magnitude with the upper end of the hormetic curve approaching the estimated no-observed-effect level (NOEL) for the particular endpoint. Based on the evaluation criteria, high to moderate evidence of hormesis was observed in studies comprised of ≥ doses with <3 doses in the hormetic zone. The present analysis suggests that chem ical hormesis is a reproducible and generalizable biologic phenomenon. Over the last decade advances have been made providing mechanistic insight helpful in explaining the phenomenon of chemical hormesis in multiple biologic systems with various endpoints. The reason for the uncertainty surrounding the existence of hormesis as a “real phenomenon” is believed to be the result of its relatively infrequent observation in the literature due to experimental design considerations, especially with respect to the number of doses, range of doses, and endpoint selection.