Problems with the Numerator in Noncancer Risk Assessment. G. M. Gray and S. J. S. Baird, Harvard School of Public Health, 718 Huntington Ave., Boston, MA 02159; J. T. Cohen, Gradient Corporation, 44 Brattle St., Cambridge, MA 02138; and L. Rhomberg, Harvard Center for Risk Analysis, Harvard School of Public Health, 718 Huntington Ave., Boston, MA 02159
Traditional noncancer risk assessment divides a No Observed Adverse Effect Level (NOAEL) from a scientifically judged critical study demonstrating a critical effect by a number of uncertainty or safety factors to derive acceptable levels of exposure such as the World Health Organization’s Tolerable Daily Intake or the U.S. Environmental Protection Agency’s Reference Dose. There are several attributes of the numerator that confound efforts to characterize the uncertainty and variability in noncancer risk assessment. The NOAEL is very sensitive to experimental design, especially the number and spacing of doses and the statistical power of a study. This severely compromises the ability to compare NOAELs across chemicals and studies. The benchmark dose (BMD) approach improves upon the NOAEL and generates a more consistent point of comparison across studies. Yet problems remain. Both the NOAEL and BMD use only one study, and one endpoint, out of the abundance of data available to characterize the uncertainty and variability in toxic response to an agent. Although the BMD approach models the critical effect dose-response only a single point on the curve (the BMD itself) is ultimately used. Neither approach considers the considerable effect that dose scaling can have on the choice of critical effect. Finally, by emphasizing the low response end of the dose-response information there is a possibility that both approaches introduce adjustments for variability in both the numerator and denominator. This presentation will discuss and illustrate the shortcomings of the numerator in current noncancer risk assessment and its probabilistic extensions. The ways in which these problems are overcome in the proposed "Integrated Dose-Response Method" will be presented.
Work supported in part by Health Canada, under Contract# H1201-6-9888.