Toxicology rewrites its history and rethinks its future: Giving equal focus to both harmful and beneficial effects

• Published in: Environmental toxicology and chemistry 2011-12, Vol.30 (12), p.2658-2673
• Main Author: Calabrese, Edward J.
• Format: Article
• Language: English
• Subjects: Biphasic; Carcinogens - pharmacology; Carcinogens - toxicity; Dose-response; Dose-Response Relationship, Drug; Drug dosages; Ecotoxicology - history; Ecotoxicology - methods; Environmental Pollutants - pharmacology; Environmental Pollutants - therapeutic use; Environmental Pollutants - toxicity; Forecasting; History, 20th Century; Homeopathy - history; Homeopathy - methods; Hormesis; Hormetic; Humans; Research Design; Risk; Risk assessment; Risk Assessment - methods; Toxicology; Validation studies
• ISSN: 0730-7268; 1552-8618
• DOI: 10.1002/etc.687

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. Environ. Toxicol. Chem. 2011;30:2658–2673. © 2011 SETAC