Archives of Toxicology

, Volume 83, Issue 3, pp 227–247

Getting the dose–response wrong: why hormesis became marginalized and the threshold model accepted

Review Article

DOI: 10.1007/s00204-009-0411-5

Cite this article as:
Calabrese, E.J. Arch Toxicol (2009) 83: 227. doi:10.1007/s00204-009-0411-5


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.


Hormesis Hormetic Threshold Biphasic U-shaped J-shaped 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Department of Public Health, Environmental Health Sciences Division, School of Public Health and Health SciencesUniversity of MassachusettsAmherstUSA

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