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History of dose response.

William J Waddell¹

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

This summary is machine-generated.

The history of dose-response relationships spans three eras, highlighting Paracelsus

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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.