title: Historical blunders: how toxicology got the dose-response relationship half right.
abstract: Substantial evidence indicates that reliable examples of hormetic dose responses in the toxicological literature are common and generalizable across biological model, endpoint measured and chemical class. Further evaluation revealed that the hormetic dose response model is more common than the threshold dose response model in objective, head-to-head comparisons. Nonetheless, the field of toxicology made a profound error by rejecting the use of the hormetic dose response model in its teaching, research, risk assessment and regulatory activities over nearly the past century. This paper argues that the hormetic dose response model (formerly called the Arndt-Schulz Law) was rejected principally because of its close historical association with the medical practice of homeopathy as a result of the prolonged and bitter feud between traditional medicine and homeopathy. Opponents of the concept of hormesis, making use of strong appeals to authority, were successful in their misrepresentation of the scientific foundations of hormesis and in their unfair association of it with segments of the homeopathic movement with extreme and discreditable views. These misrepresentations became established and integrated within the pharmacology and toxicology communities as a result of their origins in and continuities with traditional medicine and subsequently profoundly impacted a broad range of governmental risk assessment activities further consolidating the rejection of hormesis. This error of judgment was reinforced by toxicological hazard assessment methods using only high and few doses that were unable to assess hormetic responses, statistical modeling processes that were constrained to deny the possibility of hormetic dose response relationships and by the modest nature of the hormetic stimulatory response itself, which required more rigorous study designs to evaluate possible hormetic responses.
authors.affiliation: Environmental Health Sciences Program, School of Public Health, University of Massachusetts, Amherst, 01003, USA. edwardc@schoolph.umass.edu
authors.forename: E J
authors.initials: EJ
authors.lastname: Calabrese
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D049672:History, 19th Century; D049673:History, 20th Century; D006705:Homeopathy / Q000266:history; D006801:Humans; D008954:Models, Biological; D010600:Pharmacology / Q000266:history; D018570:Risk Assessment; D018675:Toxicity Tests; D014116:Toxicology / Q000266:history / Q000379:methods