Brominated flame retardants such as polybrominated diphenyl ethers (PBDEs), pentabromophenol (PBP), and tetrabromobisphenol A (TBBPA) are produced in large quantities for use in electronic equipment, plastics, and building materials. Because these compounds have some structural resemblance to the thyroid hormone thyroxine (T(4)), it was suggested that they may interfere with thyroid hormone metabolism and transport, e.g., by competition with T(4) on transthyretin (TTR). In the present study, we investigated the possible interaction of several brominated flame retardants with T(4) binding to TTR in an in vitro competitive binding assay, using human TTR and 125 I-T(4) as the displaceable radioligand. Compounds were tested in at least eight different concentrations ranging from 1.95 to 500 nM. In addition, we investigated the structural requirements of these and related ligands for competitive binding to TTR. We were able to show very potent competition binding for TBBPA and PBP (10.6- and 7.1-fold stronger than the natural ligand T(4), respectively). PBDEs were able to compete with T(4)-TTR binding only after metabolic conversion by induced rat liver microsomes, suggesting an important role for hydroxylation. Brominated bisphenols with a high degree of bromination appeared to be more efficient competitors, whereas chlorinated bisphenols were less potent compared to their brominated analogues. These results indicate that brominated flame retardants, especially the brominated phenols and tetrabromobisphenol A, are very potent competitors for T(4) binding to human transthyretin in vitro and may have effects on thyroid hormone homeostasis in vivo comparable to the thyroid-disrupting effects of PCBs.

Air samples from a plant engaged in recycling electronics goods, a factory assembling printed circuit boards, a computer repair facility, offices equipped with computers, and outdoor air have been analyzed with respect to their content of brominated hydrocarbon and phosphate ester flame retardants. Polybrominated diphenyl ethers, polybrominated biphenyls, 1,2-bis(2,4,6-tribromophenoxy)-ethane, tetrabromobisphenol A, and organophosphate esters were all detected in the indoor air samples, with the highest concentrations being detected in air from the recycling plant. In air from the dismantling hall at the recycling plant the average concentrations of decabromodiphenyl ether, tetrabromobisphenol A, and triphenyl phosphate were 38, 55, and 58 pmol/m3, respectively. Significantly higher levels of all of these additives were present in air in the vicinity of the shredder at the dismantling plant. This is the first time that 1,2-bis(2,4,6-tribromophenoxy)-ethane and several arylated phosphate esters are reported to be contaminants of air in occupational settings. At all of the other sites investigated, low levels of flame retardants were detected in the indoor air. Flame retardants associated with airborne particles, present at elevated levels, pose a potential health hazard to the exposed workers.

The aim of the present study was to model apparent serum half-lives of polybrominated diphenyl ethers (PBDEs) with 7–10 bromine substituents. Workers with occupational exposure to PBDEs have elevated serum levels of PBDEs, but these substances are also found in the general population and are ubiquitous environmental contaminants. The calculations were based on exposure assessments of rubber workers (manufactured flame-retarded rubber compound) and electronics dismantlers who donated blood during a period with no work-related exposures to PBDEs, and referents without any known occupational exposure (clerks, cleaners, and abattoir workers). The workers had previously been found to have elevated levels of high- and medium-brominated diphenyl ethers compared with the referent populations. We performed nonlinear mixed-effects modeling of kinetics, using data from previous and present chemical analyses. The calculated apparent half-life for decabromodiphenyl ether (BDE-209) was 15 days (95% confidence interval, 11–18 days). The three nona-BDEs and four octa-BDE congeners were found to have half-lives of 18–39 and 37–91 days, respectively. BDE-209 has a short half-life in human blood. Because BDE-209 is commonly present in humans in general, the results of this study imply that humans must be more or less continuously exposed to BDE-209 to sustain the serum concentrations observed. BDE-209 is more readily transformed and/or eliminated than are lower brominated diphenyl ether congeners, and human health risk must be assessed accordingly.

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Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental contaminants due to their use as flame retardants. Similarly to PCBs, the PBDEs are metabolized to hydroxylated metabolites (OH-PBDEs) in mammals. In the present study equimolar doses of seven environmentally relevant PBDE congeners were given intraperitoneally as a mixture to rats, and their blood plasma was analyzed for parent compounds and hydroxylated metabolites 1 and 5 days after dosing. Sixteen OH-PBDEs and two diOH-PBDEs were detected as PBDE metabolites in the rat plasma, a novel finding. Four OH-tetraBDEs were structurally identified by comparison (gas chromatography/mass spectrometry) with authentic reference standards. The position of the hydroxyl groups was suggested according to the mass spectrometric fragmentation patterns of the corresponding PBDE methyl ether derivatives. The OH-PBDE metabolites were dominated by hydroxyl groups in the meta- and parapositions. The results show that OH-PBDE congeners have an ability to be retained in rat blood, most likely by a mechanism similar to that of OH-PCBs. The results will be useful for determination of the origin of OH-PBDEs present in wildlife and in humans, since OH-PBDEs are also common natural products in marine environments.

BackgroundOxidative metabolism, resulting in the formation of hydroxylated polybrominated diphenyl ether (PBDE) metabolites, may enhance the neurotoxic potential of brominated flame retardants.ObjectiveOur objective was to investigate the effects of a hydroxylated metabolite of 2,2′,4,4′-tetra-bromodiphenyl ether (BDE-47; 6-OH-BDE-47) on changes in the intracellular Ca2+ concentration ([Ca2+]i) and vesicular catecholamine release in PC12 cells.MethodsWe measured vesicular catecholamine release and [Ca2+]i using amperometry and imaging of the fluorescent Ca2+-sensitive dye Fura-2, respectively.ResultsAcute exposure of PC12 cells to 6-OH-BDE-47 (5 μM) induced vesicular catecholamine release. Catecholamine release coincided with a transient increase in [Ca2+]i, which was observed shortly after the onset of exposure to 6-OH-BDE-47 (120 μM). An additional late increase in [Ca2+]i was often observed at ≥1 μM 6-OH-BDE-47. The initial transient increase was absent in cells exposed to the parent compound BDE-47, whereas the late increase was observed only at 20 μM. Using the mitochondrial uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and thapsigargin to empty intracellular Ca2+ stores, we found that the initial increase originates from emptying of the endoplasmic reticulum and consequent influx of extracellular Ca2+, whereas the late increase originates primarily from mitochondria.ConclusionThe hydroxylated metabolite 6-OH-BDE-47 is more potent in disturbing Ca2+ homeostasis and neurotransmitter release than the parent compound BDE-47. The present findings indicate that bioactivation by oxidative metabolism adds considerably to the neurotoxic potential of PBDEs. Additionally, based on the observed mechanism of action, a cumulative neurotoxic effect of PBDEs and ortho-substituted polychlorinated biphenyls on [Ca2+]i cannot be ruled out.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been identified as metabolites of PBDEs, and also as compounds of natural origin in the marine environment; however, there has only been very limited study of their presence in the abiotic environment. In the present study, OH-PBDEs were determined in samples of surface water and precipitation (rain and snow) collected from sites in Ontario, Canada. OH-PBDEs were detected in all the samples analyzed, although half of the observed peaks did not correspond to any of the 18 authentic standards available. Fluxes of sigmaOH-PBDEs ranged from 3.5 to 190 pg/m2 in snow and from 15 to 170 pg/m2/day in rain, and those were higher at three of the southern Ontario locations relative to a single northern remote site. Concentrations of sigmaOH-PBDEs ranged from 2.2 to 70 pg/L in water and from < 1 to 420 pg/g in particulate organic carbon (POC), and higher values were found near sewage treatment plant (STP) outfalls in Lake Ontario. Partition coefficients (log K(oc)) for OH-PBDEs ranged from 4.0 to 5.1. The results in this study suggest that OH-PBDEs are ubiquitous in the abiotic environment and most likely are produced through reaction of PBDEs with atmospheric OH radicals. As well, they may be present in surface waters near STPs due to oxidation of PBDEs and inflows from metabolism by humans and animals.

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