Part II: Quantitative Evaluation of Choices Used in Setting Noncancer Chronic Human Health Reference Values Across Organizations

Abstract

Environmental and public health organizations, including the World Health Organization (WHO) and the U.S. Environmental Protection Agency (USEPA), develop human health reference values (HHRV) that set "safe" levels of exposure to noncarcinogens. Here, we systematically analyze chronic HHRVs from four organizations: USEPA, Health Canada, RIVM (the Netherlands), and the U.S. Agency for Toxic Substances and Disease Registry. This study is an extension of our earlier work and both closely examines the choices made in setting HHRVs and presents a quantitative method for identifying the primary factors influencing HHRV agreement or disagreement. We evaluated 171 organizational comparisons, developing a quantitative method for identifying the factors to which HHRV agreement (that is, when both organizations considering the same data set the identical HHRV values) is most sensitive. To conduct this analysis, a Bayesian belief network was built using expert judgment, including the specific science policy choices analysis made in the context of setting an HHRV. Based on a sensitivity of findings analysis, HHRV agreement is most sensitive to the point of departure value, followed by the total uncertainty factor (UF), critical study, critical effect, animal model, and point of departure approach. This analysis also considered the specific impacts of individual UFs, with the database UF and the subchronic-to-chronic UF being identified as primary factors impacting the total UF differences observed across organizations. The sensitivity of findings analysis results were strengthened and confirmed by frequency analyses evaluating which choices most often disagreed when the HHRV and the total UF disagreed.

Part I––Comparing Noncancer Chronic Human Health Reference Values: An Analysis of Science Policy Choices

“…Based on this analysis, USEPA was more likely to use this factor than HC, RIVM, or ATSDR, with USEPA using this factor for deriving 33–49% of its HHRVs compared to 7–28% in the other organizations. Our companion article evaluates the specific rationale for using this factor and examines whether this rationale differs across organizations …”

“…The results from this analysis are consistent with those from earlier studies, demonstrating, again, the impact of scientific judgment and science policy choices on setting HHRVs . After controlling for data availability, the largest HHRV difference was 83‐fold (cyanide, free).…”

“…However, the variables are conditional and interdependent (i.e., the PODV and UF used are dependent on the critical study, critical effect, and PODA). This interdependence has been evaluated explicitly in the companion article to this analysis …”

“…These results may also identify specific characteristics of chemicals with the least or greatest degree of disagreement, characteristics that may inform future evaluations. In addition, our companion article provides a further, quantitative analysis of these variables and the interrelationships between these choices …”

“…In addition, our companion article provides a further, quantitative analysis of these variables and the interrelationships between these choices. (5)…”