Hormesis: The dose-response revolution

Hormesis, a dose-response relationship phenomenon characterized by low-dose stimulation and high-dose inhibition, has been frequently observed in properly designed studies and is broadly generalizable as being independent of chemical/physical agent, biological model, and endpoint measured. This under-recognized and -appreciated concept has the potential to profoundly change toxicology and its related disciplines with respect to study design, animal model selection, endpoint selection, risk assessment methods, and numerous other aspects, including chemotherapeutics. This article indicates that as a result of hormesis, fundamental changes in the concept and conduct of toxicology and risk assessment should be made, including (a) the definition of toxicology, (b) the process of hazard (e.g., including study design, selection of biological model, dose number and distribution, endpoint measured, and temporal sequence) and risk assessment [e.g., concept of NOAEL (no observed adverse effect level), low dose modeling, recognition of beneficial as well as harmful responses] for all agents, and (c) the harmonization of cancer and noncancer risk assessment.