Abstract
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.
Highlights
The dose–response relationship is a central concept in many biological disciplines, but especially in pharmacology, toxicology and risk assessment
In 2015, the US Nuclear Regulatory Commission called for a national debate over whether the linear-non-threshold (LNT) model for radiation risk assessment should be replaced by the hormesis dose response [1]
While the current issue is designed to assess in detail aspects of the hormetic dose–response relationship, it was deemed of value to explore the historical foundations of the hormetic dose–response within a broader context, that is, in comparison to the two other leading dose–response models, the threshold and LNT models
Summary
The dose–response relationship is a central concept in many biological disciplines, but especially in pharmacology, toxicology and risk assessment. The area of dose–response, especially with respect to low dose treatment effects, remains highly controversial and unresolved. This confusion may be highlighted with the ongoing debate over the use of the linear-no-threshold dose–response model for cancer risk assessment for ionizing radiation and chemical carcinogens. In 2015, the US Nuclear Regulatory Commission called for a national debate over whether the linear-non-threshold (LNT) model for radiation risk assessment should be replaced by the hormesis dose response [1]. While specific controversial issues associated with dose–response models have often changed over generations, the area of dose–response is an active research zone and it is expected that new insights, perspectives and judgments may emerge, with profound medical, public health and regulatory implications. This article provides the historical setting from which new research findings on dose–response models and their underlying mechanisms will emerge to both inform and possibly challenge the status quo
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