HUMAN VARIABILITY AND NONCANCER RISK ASSESSMENT - AN ANALYSIS OF THE DEFAULT UNCERTAINTY FACTOR

A 10-fold uncertainty factor is used for noncancer risk assessments to allow for possible interindividual differences between humans in the fate of the chemical in the body (kinetics) and target organ sensitivi ty (dynamics). Analysis of a database on the variability in each of th ese aspects is consistent with an even subdivision of the 10-fold fact or into 10(0.5) (3.16) for kinetics and 10(0.5) (3.16) for dynamics. A nalysis of the number of subjects in a normally and log-normally distr ibuted population which would not be covered by factors of 3.16 suppor ts this subdivision and also the use of a 10-fold factor to allow for both aspects. Analysis of kinetic data for subgroups of the population indicates that the standard default value of 3.16 for kinetics will n ot be adequate for all routes of elimination and all groups of the pop ulation. A scheme is proposed which would allow the selection of appro priate default uncertainty factors based on knowledge of the biologica l fate and effects of the chemical under review. (C) 1998 Academic Pre ss.