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A general classification of U-shaped dose-response relationships in toxicology and their mechanistic foundations

Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts 01003, USA

Linda A Baldwin

Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts 01003, USA

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.¹ An assessment of this database reveals the existence of a wide range of hormetic dose-reponse 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.

Key Words: hormesis • low dose • risk assessment • paradoxical effects • U-shaped

Human & Experimental Toxicology, Vol. 17, No. 7, 353-364 (1998)
DOI: 10.1177/096032719801700701


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