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.

Among all brominated flame retardants in use, the polybrominated diphenyl ethers (PBDEs) have been identified as being of particular environmental concern due to their global distribution and bioaccumulating properties, as observed in humans and wildlife worldwide. Still there is a need for more data on the basic characteristics of PBDEs to better understand and describe their environmental fate. Hence, the aim of this study was to investigate the photochemical degradation of PBDEs with different degrees of bromination. The photochemical degradation of 15 individual PBDEs substituted with 4-10 bromine atoms was studied in methanol/water (8:2) by UV light in the sunlight region. Nine of these were also studied in pure methanol, and four of the nine PBDEs were studied in tetrahydrofuran. The photochemical reaction rate decreased with decreasing number of bromine substituents in the molecule but also in some cases influenced by the PBDE substitution pattern. The reaction rate was dependent on the solvent in such a way that the reaction rate in a methanol/water solution was consistently around 1.7 times lower than in pure methanol and 2-3 times lower than in THF. The UV degradation half-life of decaBDE (T1/2 = 0.5 h) was more than 500 times shorter than the environmentally abundant congener 2,2',4,4'-tetraBDE (T1/2 = 12 d) in methanol/water. The quantum yields in the methanol/water solution ranged from 0.1 to 0.3. The photochemical reaction of decaBDE is a consecutive debromination from ten- down to six-bromine-substituted PBDEs. Products with less than six bromines were tentatively identified as brominated dibenzofurans and traces of what was indicated as methoxylated brominated dibenzofurans.

Polybrominated diphenyl ethers (PBDEs) are used in large quantities as additive flame retardants in plastics and textile materials. PBDEs are persistent compounds and have been detected in wildlife and in human adipose tissue and plasma samples. In this study, we investigated the (anti)estrogenic potencies of several PBDE congeners, three hydroxylated PBDEs (HO-PBDEs), and differently brominated bisphenol A compounds in three different cell line assays based on estrogen receptor (ER)-dependent luciferase reporter gene expression. In human T47D breast cancer cells stably transfected with an estrogen-responsive luciferase reporter gene construct (pEREtata-Luc), 11 PBDEs showed estrogenic potencies, with concentrations leading to 50% induction (EC(50)) varying from 2.5 to 7.3 microM. The luciferase induction of the most potent HO-PBDE [2-bromo-4-(2,4,6-tribromophenoxy)phenol] exceeded that of estradiol (E(2)), though at concentrations 50,000 times higher. As expected, brominated bisphenol A compounds with the lowest degree of bromination showed highest estrogenic potencies (EC(50) values of 0.5 microM for 3-monobromobisphenol A). In an ER alpha-specific, stably transfected human embryonic kidney cell line (293-ER alpha-Luc), the HO-PBDE 4-(2,4,6-tribromophenoxy)phenol was a highly potent estrogen with an EC(50) < 0.1 microM and a maximum 35- to 40-fold induction, which was similar to E(2). In an analogous ER beta-specific 293-ER betas-Luc cell line, the agonistic potency of the 4-(2,4,6-tribromophenoxy)phenol was much lower (maximum 50% induction compared to E(2)), but EC(50) values were comparable. These results indicate that several pure PBDE congeners, but especially HO-PBDEs and brominated bisphenol A-analogs, are agonists of both ER alpha and ER beta receptors, thus stimulating ER-mediated luciferase induction in vitro. These data also suggest that in vivo metabolism of PBDEs may produce more potent pseudoestrogens.

Methoxylated polybrominated diphenyl ethers (MeO-PBDEs) and hydroxylated PBDEs (OH-PBDEs) have recently been identified in fish and wildlife from the Baltic Sea. Both OH-PBDEs and MeO-PBDEs are known natural products, while OH-PBDEs also may be metabolites of PBDEs. The aim of the present study was to determine if the red macroalga Ceramium tenuicorne could be a source for MeO- and OH-PBDEs in the Baltic environment. Blue mussels (Mytilus edulis) from the same area were also investigated for their content of MeO- and OH-PBDEs. Seven OH-PBDEs and four MeO-PBDEs were present both in the red macroalga and the blue mussels. The mussels also contained a monochlorinated OH-tetraBDE. One of the compounds, 6-methoxy-2,2',3,4,4',5-hexabromodiphenyl ether, has never been reported to occur in the environment. The identification was based on comparison of relative retention times with reference standards, on two gas chromatographic columns of different polarities, together with comparisons of full-scan electron capture negative ionization (ECNI) and electron ionization (EI) mass spectra. It is shown that MeO-PBDEs and OH-PBDEs are present in algae, but at this stage it could not be confirmed if the compounds are produced by the alga itself or by its associated microflora and/or microfauna.

ObjectiveOur aim was to investigate exposure to polybrominated diphenyl ethers (PBDEs) in a young urban population in a developing country, with focus on potentially highly exposed children working informally as scrap scavengers at a large municipal waste disposal site. We also set out to investigate whether hydroxylated metabolites, which not hitherto have been found retained in humans, could be detected.MethodsWe assessed PBDEs in pooled serum samples obtained in 2002 from children 11–15 years of age, working and sometimes also living at the municipal waste disposal site in Managua, and in nonworking urban children. The influence of fish consumption was evaluated in the children and in groups of women 15–44 years of age who differed markedly in their fish consumption. Hydroxylated PBDEs were assessed as their methoxylated derivates. The chemical analyses were performed by gas chromatography/mass spectrometry, using authentic reference substances.ResultsThe children living and working at the waste disposal site showed very high levels of medium brominated diphenyl ethers. The levels observed in the referent children were comparable to contemporary observations in the United States. The exposure pattern was consistent with dust being the dominating source. The children with the highest PBDE levels also had the highest levels of hydroxylated metabolites.ConclusionsUnexpectedly, very high levels of PBDEs were found in children from an urban area in a developing country. Also, for the first time, hydroxylated PBDE metabolites were found to bioaccumulate in human serum.