In vitro exposure of DE‐71, a penta‐PBDE mixture, on immune endpoints in bottlenose dolphins (Tursiops truncatus) and B6C3F1 mice

Abstract

Polybrominated diphenyl ethers (PBDEs) are an emerging contaminant of concern with low level exposures demonstrating toxicity in laboratory animals and wildlife, although immunotoxicity studies have been limited. Bottlenose dolphin peripheral blood leukocytes (PBLs) and mouse splenocytes were exposed to environmentally relevant DE-71 (a penta-PBDE mixture) concentrations (0-50 µg ml(-1) ) in vitro. Natural killer (NK) cell activity and lymphocyte (B and T cell) proliferation were evaluated using the parallelogram approach for risk assessment. This study aimed to substantiate results from field studies with dolphins, assess the sensitivities between the mouse model and dolphins, and to evaluate risk using the parallelogram approach. In mouse cells, NK cell activity increased at in vitro doses 0.05, 0.5 and 25 µg DE-71 ml(-1) , whereas proliferation was not modulated. In dolphin cells, NK cell activity and lymphocyte proliferation was not altered after in vitro exposure. In vitro exposure of dolphin PBLs to DE-71 showed similar results to correlative field studies; NK cell activity in mice was more sensitive to in vitro exposure than dolphins, and the parallelogram approach showed correlation with all three endpoints to predict risk in bottlenose dolphins.

The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro

“…Our experiments were performed in serum-free conditions and thus the free PBDE concentrations may be lower in vivo where serum binding proteins for PBDE are present. The concentration range of DE-71 used in this study were similar to former in vitro studies with PBDEs [61;62]. The lowest concentration of DE-71 used in our study was 0.01 mg DE-71/L.…”

In Vitro Assessment of Activation of Baikal Seal (Pusa sibirica) Peroxisome Proliferator-Activated Receptor α by Polybrominated Diphenyl Ethers

“…Although these PBDEs have been phased out, some PBDE congeners are still being detected in the environment including soil, sediment, air, water, and biota . In addition, many of these PBDEs are bioaccumulated in humans and wildlife through the food chain owing to their high persistency and lipophilicity. , Previous studies have focused on various toxic effects induced by PBDEs, such as developmental toxicology, , neurotoxicity, , immunotoxicity, , and endocrine disruption. , It has been suggested that these adverse effects may be mediated by estrogen receptor (ER), , aryl hydrocarbon receptor (AhR), , constitutive active/androstane receptor (CAR), and pregnane X receptor (PXR) …”

Effects of the Commercial Flame Retardant Mixture DE-71 on Cytokine Production by Human Immune Cells

“…The chosen concentrations of DE-71 were based on previous in vitro studies [ 29 , 33 ], which exceeded PBDE levels found in the indoor environment in Denmark [ 10 ], as well as in the blood of Danish donors [ 22 , 34 ]. These studies showed correlations between PBDEs in dust and blood, suggesting that dust was a primary exposure source in humans.…”