A general classification of U-shaped dose-response relationships in toxicology and their mechanistic foundations.
The development of a comprehensive database of chemical hormetic responses (i.e., U- or inverted U-shaped dose-response relationships) using objective a priori study design, statistical and study replication criteria has recently been reported. An assessment of this database reveals the existence of a wide range of hormetic dose-response relationships including those demonstrating a direct stimulation or an overcompensation response to a disruption of homeostasis. These two broad types of hormetic responses are affected by temporal factors and display unique patterns of dose-range stimulation, magnitude of stimulatory response and relationship of the maximum stimulatory response to the NOAEL. A general classification of U-shaped dose-response relationships is proposed to provide a more organized framework to evaluate the highly distinctive and diverse hormetic responses within the context of establishing underlying biological mechanisms and exploring risk assessment implications.
Calabrese
E J
EJ
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst 01003, USA.
Baldwin
L A
LA
D000818:Animals; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015233:Models, Statistical; D018570:Risk Assessment / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*