The failure of dose-response models to predict low dose effects: a major challenge for biomedical, toxicological and aging research.

Recent detailed evaluations of the pharmacological, toxicological, and biogerontological literature indicate that the hormetic dose-response is quite common and highly generalizable by biological model, endpoint, and chemical class. Head-to-head comparisons of the hormetic model with the traditional threshold model have revealed the hormetic model to occur with considerably greater frequency in the biomedical literature. Despite these developments, the history of both pharmacology and toxicology reflects a strong acceptance and centralizing of the threshold model concept while profoundly marginalizing of the hormetic dose-response. This commentary will address why the biomedical community especially those in the areas of pharmacology and toxicology made an incorrect judgment that the most fundamental nature of the dose-response was threshold rather than hormetic and why this conclusion has continued to dominate these fields and their numerous applications despite convincing evidence to the contrary. These findings have particular relevance to the area of biogerontology since this discipline often resides at the pharmacological-toxicological interface.