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Toxicologic Pathology
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The Marginalization of Hormesis

Edward J. Calabrese

Department of Environmental Health Sciences, School of Public Health, University of Massachusetts, Amherst, Massachusetts

Linda A. Baldwin

Department of Environmental Health Sciences, School of Public Health, University of Massachusetts, Amherst, Massachusetts

Despite the substantial development and publication of highly reproducible toxicological data, the concept of hormetic dose-response relationships was never integrated into the mainstream of toxicological thought. Review of the historical foundations of the interpretation of the bioassay and assessment of competitive theories of dose-response relationships lead to the conclusion that multiple factors contributed to the marginalization of hormesis during the middle and subsequent decades of the 20th Century. These factors include the following: (a) the close association of hormesis with homeopathy, which led to the hostility of modern medicine toward homeopathy, thereby creating a guilt-by-association framework, and the carryover influence of that hostility toward hormesis in the judgements of medically based pharmacologists/toxicologists; (b) the emphasis of high-dose effects linked with a lack of appreciation of the significance of the implications of low-dose stimulatory effects; (c) the lack of an evolution-based mechanism(s) to account for hormetic effects; and (d) lack of appropriate scientific advocates to counter aggressive and intellectually powerful critics of the hormetic perspective.

Key Words: Low dose • stimulation • β-curve

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Toxicologic Pathology, Vol. 27, No. 2, 187-194 (1999)
DOI: 10.1177/019262339902700206
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