The marginalization of hormesis.
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.