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Related Experiment Videos

Hormesis, Gompertz functions, and risk assessment.

H Boxenbaum1, P J Neafsey, D J Fournier

  • 1Drug Metabolism Department, Merrell Dow Research Institute, Cincinnati, Ohio 45215-6300.

Drug Metabolism Reviews
|January 1, 1988
PubMed
Summary

Low doses of toxic substances may offer health benefits, a concept known as hormesis. This phenomenon, observed across centuries and in modern studies, challenges traditional risk assessment by suggesting beneficial effects at low exposure levels.

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Area of Science:

  • Toxicology
  • Gerontology
  • Biostatistics

Background:

  • Historical literature suggests low doses of toxic substances can be beneficial.
  • Modern bioassay studies reveal low-dose exposure can induce beneficial changes, promoting health and longevity (longevity hormesis).
  • This phenomenon is nonspecific, reversible, and operates via an unknown mechanism.

Purpose of the Study:

  • To review historical and modern evidence for low-dose benefits of toxic substances.
  • To model the phenomenon of longevity hormesis kinetically.
  • To discuss the implications for current risk assessment practices.

Main Methods:

  • Historical literature survey.
  • Assessment of mortality data from modern bioassay studies.

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  • Kinetic modeling using age-specific mortality rate and a generalized Gompertz function.

    • Main Results:

    • Evidence supports the concept of hormesis, where low-dose toxicant exposure can be beneficial.
    • A kinetic model suggests hormetic reduction in injury can offset aging and toxicity-related mortality.
    • A net reduction in age-specific mortality rate is observed at low exposure levels.

    Conclusions:

    • The principle of hormesis, or low-dose benefits, is supported by historical and modern data.
    • Current risk assessment models, assuming higher-dose effects solely dictate low-dose responses, are qualitatively incorrect.
    • Re-evaluation of toxicological risk assessment is needed to incorporate hormetic effects.