Human Variability in Susceptibility to Toxic Chemicals I. Noncarcinogens

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The tenfold 'safety' factor traditionally used to guard against human interindividual differences in susceptibility to toxicity is not based on human observations. Some support for a tenfold dose-reduction is based upon the distribution of profit slopes from acute toxicity in animals. Although human data is preferable, epidemiologic data are unlikely to have precise exposure measurements. To study human interindividual variability the authors used papers from the recent pharmacological literature to construct a data base of individual measurements of key pharmacokinetic parameters for specific substances (mostly drugs). The parameters studied, elimination halflives, maximal blood concentrations and area under the curve (AUC) of blood concentrations are only components of overall susceptibility to toxic agents, and do not include variability parameters that would affect exposure and response, nor from age or illness. 72 of the 101 data sets studied were positively skewed, indicating that the distributions are generally closer to log-normal distribution than a normal distribution.


U.S. EPA. Human Variability in Susceptibility to Toxic Chemicals I. Noncarcinogens. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/8-86/033 (NTIS PB87101242), 1986.