Human interindividual variability in parameters related to health risks.

Area of Science:

• Environmental Health
• Toxicology
• Risk Assessment

Background:

• Health risk analyses require understanding variability in exposure and individual susceptibility.
• A toxicity/susceptibility database is being developed for quantitative distributional analyses of non-cancer toxic risks.

Purpose of the Study:

• To review existing data on variability in parameters relevant to health risk analyses.
• To identify key steps in the pathway from exposure to biological response where variability is significant.

Main Methods:

• Review of data on exposure-related parameters and individual susceptibility to toxicity.
• Categorization of parameters across the exposure-to-response pathway.
• Analysis of variability in different parameter types.

Main Results:

• Significant variability exists across all steps of the exposure-to-response pathway.
• The greatest variability is observed in "functional reserve capacity," reflecting individual differences in physiological response.
• Population distributions of physiological parameters (e.g., Low Density Lipoprotein Cholesterol) can inform toxic susceptibility.

Conclusions:

• Individual differences in functional reserve capacity are a major source of variability in toxic susceptibility.
• Direct studies of population distributions of key physiological parameters can aid in estimating toxic susceptibility.
• This approach provides a foundation for quantitative distributional analyses of non-cancer toxic risks.