School of Public Health and Health Sciences, Department of Public Health, University of Massachusetts, Amherst, Massachusetts, USA.
Environ Toxicol Chem. 2011 Dec;30(12):2658-73. doi: 10.1002/etc.687. Epub 2011 Oct 26.
This paper assesses how medicine adopted the threshold dose-response to evaluate health effects of drugs and chemicals throughout the 20th century to the present. Homeopathy first adopted the biphasic dose-response, making it an explanatory principle. Medicine used its influence to discredit the biphasic dose-response model to harm homeopathy and to promote its alternative, the threshold dose-response. However, it failed to validate the capacity of its model to make accurate predictions in the low-dose zone. Recent attempts to validate the threshold dose-response indicate that it poorly predicts responses below the threshold. The long marginalized biphasic/hormetic dose-response model made accurate predictions in these validation studies. The failure to accept the possibility of the hormetic-biphasic dose-response during toxicology's dose-response concept formative period, while adopting the threshold model, and later the linear no-threshold model for carcinogens, led toxicology to adopt a hazard assessment process that involved testing only a few very high doses. This created the framework that toxicology was a discipline that only studied harmful responses, ignoring the possibility of benefit at low doses by the induction of adaptive mechanisms. Toxicology needs to assess the entire dose-response continuum, incorporating both harmful and beneficial effects into the risk assessment process.
本文评估了医学在 20 世纪至今如何采用阈值剂量反应来评估药物和化学物质对健康的影响。顺势疗法最早采用双相剂量反应,使其成为一种解释性原则。医学利用其影响力诋毁双相剂量反应模型,以伤害顺势疗法并推广其替代方法——阈值剂量反应。然而,它未能验证其模型在低剂量区做出准确预测的能力。最近验证阈值剂量反应的尝试表明,它在阈值以下的预测能力很差。长期被边缘化的双相/适应剂量反应模型在这些验证研究中做出了准确的预测。在毒理学剂量反应概念形成期,毒理学未能接受适应-双相剂量反应的可能性,而采用了阈值模型,后来又采用了线性无阈值模型来评估致癌物,这导致毒理学采用了一种仅测试少数非常高剂量的危害评估过程。这为毒理学创造了一种框架,即毒理学是一门只研究有害反应的学科,忽略了通过诱导适应机制在低剂量下可能产生的益处。毒理学需要评估整个剂量反应连续体,将有害和有益的影响纳入风险评估过程。