Limits to chemical hormesis as a dose–response model in health risk assessment

Abstract

This review presents and discusses the extent to which chemical hormesis meets five important requirements for performance of any dose–response model in the toxicological and regulatory sciences. These include (1) the requirement that there be a documented and accepted mechanistic basis for the dose–response model's plausible role and use in health risk assessment; (2) the requirement that any newly proposed dose–response methodology can be compared with current models as to reliability and scientific validity; (3) the requirement that the underlying reliability and stability of the model be established as to its temporal aspects, that is, minimal temporal lag between stressor contact and biological or toxicological response and temporal stability expressed throughout the prevailing relationship; (4) the requirement that the dose–response model be as broadly applicable as other dose–response methodologies being applied in human health risk assessment; and, (5) the requirement that any dose–response model proposed as default methodology can be characterized as to variability and uncertainty and will have a minimal likelihood of harm to the health of impacted populations. This review includes a brief treatment of definitions of hormesis and its place in nonmonotonic dose–response relationships. Overall, critical evaluation of chemical hormesis as a dose–response model in risk assessment shows it to have significant limits within the five requirements. These limits will impede any acceptance of chemical hormesis as a default approach in health risk assessment.