Historical blunders: how toxicology got the dose-response relationship half right

Area of Science:

• Toxicology and Pharmacology
• Dose-Response Relationships
• Scientific History

Background:

• The hormetic dose response model, also known as the Arndt-Schulz Law, is frequently observed across various biological models and chemical classes.
• Objective comparisons show hormesis is more prevalent than the threshold model.
• Toxicology has largely ignored hormesis for nearly a century.

Observation:

• The rejection of hormesis stemmed from its historical association with homeopathy and a feud with traditional medicine.
• Misrepresentations and appeals to authority led to hormesis being unfairly linked to extreme homeopathic views.
• Established toxicological practices, including limited dose testing and statistical constraints, hindered hormesis recognition.

Findings:

• Hormetic dose responses are common and generalizable in toxicological data.
• The threshold model is less common than hormesis in direct comparisons.
• Historical biases and methodological limitations caused the exclusion of hormesis from toxicology.

Implications:

• The historical rejection of hormesis represents a significant error in toxicology, impacting research and risk assessment.
• Revisiting and integrating the hormetic dose response model is essential for advancing toxicological science.
• Improved study designs and statistical approaches are needed to accurately assess hormetic effects.