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Metabolism of Brominated Flame Retardants in Human Astrocytes and Effects on Thyroid Hormone HomeostasisEPA Grant Number: FP917496
Title: Metabolism of Brominated Flame Retardants in Human Astrocytes and Effects on Thyroid Hormone Homeostasis
Investigators: Roberts, Simon Clay
Institution: Duke University
EPA Project Officer: Cobbs-Green, Gladys M.
Project Period: August 27, 2012 through August 26, 2015
Project Amount: $126,000
RFA: STAR Graduate Fellowships (2012) RFA Text | Recipients Lists
Research Category: Academic Fellowships , Fellowship - Environmental Chemistry
PBDEs are flame retardants used in consumer products, including furniture, electronics and textiles. Numerous studies have shown that PBDEs may affect human health via several mechanisms, including perturbed neurodevelopment and disruption of the thyroid hormone system. The central hypothesis of this proposed study is that PBDEs and/or their metabolites impair thyroid hormone metabolism in astrocytes contributing to impacts on neurodevelopment.
Cultured astrocyte cells will be used to assess the toxicity of PBDEs. First, the metabolism of PBDEs in astrocytes will be evaluated to determine whether hydroxylated PBDEs are formed at the blood-brain barrier. Second, thyroid hormone metabolism will be evaluated in cells exposed to PBDEs to determine whether PBDEs affect thyroid hormone levels at the blood-brain barrier. Finally, the expression of several genes will be evaluated in cultured astrocytes exposed to PBDEs to determine whether PBDEs affect thyroid hormone metabolism via interactions with various nuclear receptors in the cells.
In this proposed study, hydroxylated PBDEs and brominated phenols likely will be formed in astrocytes as a result of cytochrome p450-mediated metabolism. Previous studies have shown that polychlorinated biphenyls (PCBs) affect the regulation of thyroid hormones at the blood-brain barrier by increasing the activity of thyroid hormone deactivating enzymes (e.g., sulfotransferases) and by decreasing the activity of thyroid hormone activating enzymes (e.g., Type 2 deiodinase). It is likely that similar results will be observed with PBDEs because of their structural similarity to PCBs.
Potential to Further Environmental/Human Health Protection
The assessment of specific mechanisms of toxicity is vital for risk assessments to make informed decisions involving the management of PBDEs. Even though the commercial use of PBDEs has decreased, large reservoirs of these compounds exist in consumer products, and human exposure to PBDEs in indoor environments likely will continue for decades. Knowledge of toxic mechanisms with dose-response relationships will allow for better understanding of potential human health effects, particularly for children, who receive elevated exposures during critical windows of development. In addition, this knowledge will help facilitate the management of PBDEs in sources such as e-waste and commercial products containing PBDEs.