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Assessment of the Cytotoxic and Immunomodulatory Effects of Substances in Human Precision-cut Lung Slices
Published on: May 9, 2018
Part I--Comparing Noncancer Chronic Human Health Reference Values: An Analysis of Science Policy Choices
Elizabeth Holman1, Royce Francis2, George Gray3
1Office of Pesticide Programs, Office of Chemical Safety and Pollution Prevention, U.S. Environmental Protection Agency, Washington, DC, USA.
Abstract:
The goal of this study was to systematically evaluate the choices made in deriving a chronic oral noncancer human health reference value (HHRV) for a given chemical by different organizations, specifically those from the U.S. Environmental Protection Agency, Health Canada, RIVM (the Netherlands), and the U.S. Agency for Toxic Substances and Disease Registry. This analysis presents a methodological approach for comparing both the HHRVs and the specific choices made in the process of deriving an HHRV across these organizations. Overall, across the 96 unique chemicals and 171 two-way organizational comparisons, the HHRV agreed approximately 26% of the time. A qualitative method for identifying the primary factors influencing these HHRV differences was also developed, using arrays of HHRVs across organizations for the same chemical. The primary factors identified were disagreement on the critical or principal study and differential application of the total uncertainty factor across organizations. Of the cases where the total UF was the primary factor influencing HHRV disagreement, the database UF had the greatest influence.
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