title: Getting the dose-response wrong: why hormesis became marginalized and the threshold model accepted.
abstract: The dose-response relationship is central to the biological and biomedical sciences. During the early decades of the twentieth century consensus emerged that the most fundamental dose-response relationship was the threshold model, upon which scientific, health and medical research/clinical practices have been based. This paper documents that the scientific community made a fundamental error on the nature of the dose response in accepting the threshold model and in rejecting the hormetic-biphasic model, principally due to conflicts with homeopathy. Not only does this paper detail the underlying factors leading to this dose response decision, but it reveals that the scientific community never validated the threshold model throughout the twentieth century. Recent findings indicate that the threshold model poorly predicts responses in the low dose zone whereas its dose response "rival", the hormesis model, has performed very well. This analysis challenges a key foundation upon which biological, biomedical and clinical science rest.
authors.affiliation: Department of Public Health, Environmental Health Sciences Division, School of Public Health and Health Sciences, University of Massachusetts, Morrill I, N344, Amherst, MA 01003, USA. edwardc@schoolph.umass.edu
authors.forename: Edward 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; D014116:Toxicology / Q000266:history