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.
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Effort sponsored by the Air Force Office of Scientific Research, Air Force Material Command, USAF, under grant number FA9550-07-1-0248. The US Government is authorized to reproduce and distribute for governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsement, either expressed or implied, of the Air Force Office of Scientific Research or the US Government.
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Calabrese, E.J. Getting the dose–response wrong: why hormesis became marginalized and the threshold model accepted. Arch Toxicol 83, 227–247 (2009). https://doi.org/10.1007/s00204-009-0411-5
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DOI: https://doi.org/10.1007/s00204-009-0411-5