Record Display for the EPA National Library Catalog

RECORD NUMBER: 31 OF 76

Main Title Human Variability in Susceptibility to Toxic Chemicals: A Preliminary Analysis of Pharmacokinetic Data from Normal Volunteers.
Author Hattis, D. ; Erdreich, L. ; Ballew, M. ;
CORP Author Environmental Protection Agency, Cincinnati, OH. Environmental Criteria and Assessment Office. ;Massachusetts Inst. of Tech., Cambridge. Center for Technology, Policy and Industrial Development.
Year Published 1987
Report Number EPA/600/J-87/320;
Stock Number PB88-196324
Additional Subjects Risk analysis ; Toxicity ; Humans ; Dose ; Variability ; Reprints ; Toxic substances ; Pharmacokinetic parameters ; Susceptibility
Holdings
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Status
NTIS  PB88-196324 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 12p
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.