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Evaluating the relative responsiveness of health effects to exposure to polychlorinated biphenyl (PCB) mixtures in mammalian model systems
Citation:
Weitekamp, C., D. Kapraun, C. Chiang, L. Carlson, K. Christensen, AND G. Lehmann. Evaluating the relative responsiveness of health effects to exposure to polychlorinated biphenyl (PCB) mixtures in mammalian model systems. SOT, Nashville, TN, March 19 - 23, 2023. https://doi.org/10.23645/epacomptox.22263919
Impact/Purpose:
Exposure to polychlorinated biphenyls (PCBs) has been associated with a range of adverse health effects. However, it remains unclear if certain health outcomes are more sensitive to PCB exposures. In this work, we used systematic review methods to compile dose-response information for health outcomes across a wide range of PCB mixtures. From these data, we assessed the relative sensitivity of health outcomes by comparing lowest observed adverse effect levels. Taken together with factors such as the strength of evidence available to support conclusions about causal relationships between PCB exposure and health effects and the relative biological significance of each effect, identification of the most sensitive effects of PCB exposure could provide a basis for prioritizing outcomes for human health risk assessment.
Description:
Polychlorinated biphenyls (PCBs) are a group of chemicals that occur in the environment as mixtures of individual congeners. Despite a large volume of literature documenting adverse health effects from exposure to these mixtures, the relative sensitivity of various health outcomes to PCB exposure, especially at low, environmentally relevant levels, remains unclear. We used systematic review methods to compile dose-response information for health outcomes across a wide range of PCB mixtures. We identified 526 references that included health effect data for select nonhuman mammalian species of any lifestage exposed in vivo to PCB mixtures containing four or more congeners. For each study, we identified and extracted lowest observed adverse effect levels (LOAELs) and compared the responsiveness of health outcomes based on administered doses, human equivalent doses, and estimated internal doses of various PCB mixtures. Given the lipophilicity and biopersistence of PCBs, internal tissue levels continually increase with repeated dosing, an important aspect of pharmacokinetic behavior that is not accounted for when making comparisons based on administered dose. As such, we found that the apparent sensitivity of specific health outcomes depends, to some extent, on the dose metrics considered. Taken together with factors such as the strength of evidence available to support conclusions about causal relationships between PCB exposure and health effects and the relative biological significance of each effect, identification of the most sensitive effects of PCB exposure could provide a basis for prioritizing outcomes for human health risk assessment.
URLs/Downloads:
DOI: Evaluating the relative responsiveness of health effects to exposure to polychlorinated biphenyl (PCB) mixtures in mammalian model systems
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