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History of dose response
1Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, KY, USA. bwaddell@louisville.edu
The Journal of Toxicological Sciences
|February 2, 2010
Summary
The history of dose-response relationships spans three eras, highlighting Paracelsus
Area of Science:
- Toxicology and pharmacology.
- Environmental health and risk assessment.
- Chemical safety and regulatory science.
Background:
- The dose-response curve, or chemical concentration-effect relationship, is fundamental to understanding chemical toxicity.
- Historical analysis of dose-response curves reveals critical shifts in toxicological understanding and methodology.
- Key figures like Paracelsus recognized the importance of dose in determining chemical toxicity.
Observation:
- The history of dose-response analysis can be broadly categorized into three eras: Preclassical, Classical, and Current.
- The Classical Era (approx. 1900-1965) saw significant advancements in the parameters used for data analysis.
- The Current Era, beginning in the mid-1970s, is marked by the adoption of the linearized multistage model.
Findings:
- Paracelsus (1493-1541) is credited as the first to emphasize the critical role of dose in chemical toxicity.
- A significant error in modern toxicology is the use of a linear scale for dose in the linearized multistage model for DNA-reactive carcinogens.
- The Classical Era established that dose should be plotted on a logarithmic scale, a principle now often ignored.
Implications:
- Plotting dose on a linear scale distorts dose-response curves at low doses, hindering accurate risk assessment.
- Failure to use logarithmic scales for dose can impede the detection of relationships between carcinogen exposure and cancer development.
- Revisiting and adhering to historical principles of dose-response analysis is crucial for accurate toxicological evaluations.
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