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

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.

High doses of ethylenediurea (EDU) as soil drenches did not increase leaf N content or cause phytotoxicity in willow grown in fertile soil

“…EDU1600 did not affect any physiological traits whereas EDU800 did affect some, especially J max and C i :C a which were significantly increased and decreased, respectively. This phenomenon where EDU800 increased J max (or decreased C i :C a ) whereas EDU1600 did not affect it indicates hormesis, a biological phenomenon where a biphasic response of an organism to an agent occurs in the framework of contrasting responses between low and high doses of an agent (Calabrese, 2016;Calabrese et al, 1999). That is, EDU800-induced stimulation was below the no-observed-adverse-effect level (NOAEL) and EDU1600 was the NOAEL.…”

“…The plant size remained indifferent between EDU treatments at the end of the experiment, in agreement with earlier experiments where EDU did not affect plant morphology under quite low O 3 exposures (Agathokleous et al, 2014(Agathokleous et al, , 2016cAinsworth and Ashmore, 1992;Ashrafuzzaman et al, 2017). These results may suggest an indirect EDU-induced stimulation of plants at dosespecific thresholds (Agathokleous et al, 2016a;Kostka-Rick and Manning, 1993a,b) through disruptions in homeostasis that lead to overcompensation (Calabrese, 2014(Calabrese, , 2016Agathokleous, 2017). FM and DM were lower in EDU800 and EDU1600 plants than in EDU0 plants.…”

Homoeopathic Treatment of Chronic Hepatitis C Virus

“…Nano particle on entering the peripheral nervous system of the patient through neuropeptides and immunopeptides reaches the central nervous system to release the unusal imbalance on the emotional and mental state that has led to the pathological state in patient. The brain communication along with the electromagnetic resonance in homeopathy collectively is characterized as the vital force [10][11][12][13][14][15][16] . The main homoeopathic medicines used for the treatment of Mrs Tahira included: Chelidonium majus, Phosphorus, Lycopodium, Natrum phosphoricum, Natrum sulphururicum, Lachesis, China officinalis, Arnica montana.…”

The hazards of hazard identification in environmental epidemiology

“…A second frequent and important set of assumptions concerns the stage following hazard identification, namely quantitative risk assessment. Over the last half a century a large number of papers has been written exploring the forms and the regulatory implications of exposure-response (dose-response) curves, a key and permanently debated issue being the presence or absence of a threshold of exposure below which no response occurs [ 17 , 18 ]. This “fires back” into hazard identification, because if a threshold exists an agent would qualify as “hazard” only above the threshold level of exposure, a fact of great public health importance..…”