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Int. J. Mol. Sci. 2016, 17(12), 2034; doi:10.3390/ijms17122034

The Emergence of the Dose–Response Concept in Biology and Medicine

School of Public Health & Health Sciences, Environmental Health Sciences, Morrill I-N344, University of Massachusetts, Amherst, MA 01003, USA
Academic Editors: Guido R. M. M. Haenen, Aalt Bast and Mireille M. J. P. E. Sthijns
Received: 11 October 2016 / Revised: 21 November 2016 / Accepted: 22 November 2016 / Published: 5 December 2016
(This article belongs to the Special Issue Hormesis and Transhormesis in Toxicology and Risk Assessment)
View Full-Text   |   Download PDF [954 KB, uploaded 5 December 2016]   |  


A historical assessment of the origin of the dose–response in modern toxicology and its integration as a central concept in biology and medicine is presented. This article provides an overview of how the threshold, linear and biphasic (i.e., hormetic) dose–response models emerged in the late 19th and early 20th centuries and competed for acceptance and dominance. Particular attention is directed to the hormetic model for which a general description and evaluation is provided, including its historical basis, and how it was marginalized by the medical and pharmacology communities in the early decades of the 20th century. View Full-Text
Keywords: hormesis; dose–response; biphasic; linear non-threshold; threshold; adaptive response; history of science hormesis; dose–response; biphasic; linear non-threshold; threshold; adaptive response; history of science

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Calabrese, E.J. The Emergence of the Dose–Response Concept in Biology and Medicine. Int. J. Mol. Sci. 2016, 17, 2034.

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