HUMAN VARIABILITY IN SUSCEPTIBILITY TO TOXIC CHEMICALS: A PRELIMINARY ANALYSIS OF PHARMACOKINETIC DATA FROM NORMAL VOLUNTEERS
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Abstract
The tenfold 'uncertainty' factor traditionally used to guard against human interindividual differences in susceptibility to toxicity is not based on human observations. To begin to build a basis for quantifying an important component of overall variability in susceptibility to toxicity, a data base has been constructed of individual measurements of key pharmacokinetic parameters for specific substances (mostly drugs) in groups of at least five healthy adults. 72 of the 101 data sets studied were positively skewed, indicating that the distributions are generally closer to expectations for log-normal distributions than for normal distributions. Measurements of interindividual variability in elimination half-lives, maximal blood concentrations, and AUC (area under the curve of blood concentration by time) have median values of log sub 10 geometric standard deviations in the range of 0.11-0.145. For the median chemical, therefore, a tenfold difference in these pharmacokinetic parameters would correspond to 7-9 standard deviations in populations of normal healthy adults.
Citation
Hattis, D., L. Erdreich, AND M. Ballew. HUMAN VARIABILITY IN SUSCEPTIBILITY TO TOXIC CHEMICALS: A PRELIMINARY ANALYSIS OF PHARMACOKINETIC DATA FROM NORMAL VOLUNTEERS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-87/320 (NTIS PB88196324), 1987.
Additional Information
Pub. in Risk Analysis, v7 n4 p415-424 1987. See also PB87-101242. repared in cooperation with Massachusetts Inst. of Tech., Cambridge. Center for Technology, Policy and Industrial Development.