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Getting the dose-response wrong: why hormesis became marginalized and the threshold model accepted.

Edward J Calabrese¹

¹Department of Public Health, Environmental Health Sciences Division, School of Public Health and Health Sciences, University of Massachusetts, Morrill I, N344, Amherst, MA 01003, USA. edwardc@schoolph.umass.edu

Archives of Toxicology

|February 24, 2009

Summary

The scientific community wrongly adopted a threshold model for dose-response relationships, ignoring the hormetic-biphasic model. This error, rooted in historical conflicts, impacts biological and clinical science foundations.

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Area of Science:

Biological Sciences
Biomedical Sciences
Clinical Practices

Background:

The threshold model became the consensus for dose-response relationships in early 20th-century biological and biomedical sciences.
This model has underpinned scientific, health, and medical research and clinical practices for decades.
The historical rejection of the hormetic-biphasic model was influenced by conflicts with homeopathy.

Observation:

The scientific community's acceptance of the threshold model was not based on validation throughout the 20th century.
Recent research indicates the threshold model demonstrates poor predictive accuracy in low-dose zones.
Conversely, the hormesis model has shown strong performance, particularly in low-dose scenarios.

Findings:

This analysis reveals a fundamental error in the scientific community's understanding of dose-response relationships.
The widespread adoption of the threshold model was a decision influenced by factors beyond scientific validation.
The hormetic-biphasic model, previously rejected, is now shown to be more effective, especially at low doses.

Implications:

Challenges a foundational principle in biological, biomedical, and clinical sciences.
Suggests a need to re-evaluate established dose-response paradigms.
Highlights the potential impact of historical biases on scientific consensus and practice.