Addressing human variability in risk assessment--the robustness of the intraspecies uncertainty factor.

Addressing human variability and sensitive subpopulations is one of the challenges of risk assessment and is an important aspect of the Food Quality Protection Act, the law passed in 1996 that regulates food use pesticides in the United States. The intraspecies uncertainty factor is intended to address differences in susceptibility within the human population. This paper examines the history and scientific basis for the intraspecies uncertainty factor. Our best source of knowledge about human variability in the response to chemicals comes from clinical trials of pharmaceuticals. This large body of data allows both qualitative and quantitative characterization of variability in pharmacokinetic and pharmacodynamic parameters in the general population and in subgroups such as children. The preponderance of evidence in the areas of pharmacodynamics and pharmacokinetics supports the routine use of an intraspecies uncertainty factor in the range of 1-10 as being protective of greater than 99% of the human population. The intraspecies uncertainty factor is highly protective of various subpopulations, including infants and children.

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