Hormesis: implications for cancer risk assessment

Current guidelines for cancer risk assessment emphasize a toxicant's "mode of action", rather than its empirically derived dose-response relationship, for determining whether linear low-dose extrapolation is appropriate. Thus, for reasons of policy, demonstration of hormesis is generally insufficient to justify a non-linear approach, although it may provide important insights into the actions of toxicants. We evaluated dose-response characteristics of four carcinogens reported to have hormetic dose-response curves: cadmium chloride; ionizing radiation; PAHs; and, 2,3,7,8-TCDD. For each, the study that documented hormesis in one organ also provided evidence of non-hormetic dose-responses in other organs or non-hormetic responses for seemingly similar carcinogens in the same species and organs. Such inconsistency suggests toxicologic reasons that the finding of hormesis alone is not sufficient to justify use of non-linear low-dose extrapolations. Moreover, available data in those examples are not sufficient to know whether hormesis is a property of the toxicants, the target organ, or the exposed species. From the perspectives of cancer risk assessment, the greatest informational value of hormesis may be that it provokes mechanistic studies intended to explain why hormesis occurs.