poses of the exercise in Figure 10-1. Reinstating this factor would not substantively change the conclusion about the consistency in reference concentrations.

The graphical display in Figure 10-1 shows a distribution of sample reference values based on neurotoxic effects observed in epidemiologic studies, controlled human experiments involving healthy volunteers, and animal experiments involving different species. Exposure ranged from chronic to acute. The studies involved different neurotoxic end points that are differentially sensitive to tetrachloroethylene exposure. Whereas uncertainty factors applied to a point of departure adjust uncertainties specific to their corresponding studies, the collective distribution of reference values provides an overarching measure of uncertainties, weight of evidence, sensitivities, and other sources of variation among different studies.

This approach could also be applied to EPA’s other graphical presentations of reference values based on other noncancer end points. Such an approach would allow organ-specific reference values to be put in context with one another. For example, the degree to which sample reference values for an organ system cluster, or fail to do so, might be viewed as evidence of the degree to which different studies tap similar toxic mechanisms, kinetics, end points, or other important characteristics of a chemical.



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement