Brominated Diphenyl Ethers Research Articles

Binary Mixture Effects by PBDE Congeners (47, 153, 183, or 209) and PCB Congeners (126 or 153) in MCF-7 Cells: Biochemical Alterations Assessed by IR Spectroscopy and Multivariate Analysis

Target organisms are continuously and variously exposed to contaminant mixtures in the environment. We noted that treatment with brominated diphenyl ether (BDE)47 or polychlorinated biphenyl (PCB)126 (toxic equivalency factor [TEF] = 0.1) induces similar alterations in MCF-7 cells when these were determined using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy with multivariate analysis. Because this method appears sensitive enough to signature low-dose effects, we examined how various test agents interact in binary mixtures to induce cell alterations. MCF-7 cells were exposed for 24 h to low concentrations (10(-12) M) of polybrominated diphenyl ether (PBDE) congeners (47, 153, 183, or 209) with or without the coplanar PCB126 or nonplanar PCB153. Following treatment, ethanol-fixed cellular material was interrogated using ATR-FTIR spectroscopy; derived IR spectra in the biochemical-cell fingerprint region (1800 cm(-1)-900 cm(-1)) were then subjected to principal component analysis-linear discriminant analysis. Assuming that if two test agents independently induce the same cell alteration that in combination they'll give rise to an additive effect, we examined predicted versus observed differences in induced alterations by binary mixtures. Compared to corresponding control clusters, treatment with PBDE congener plus PCB126 appeared to cancel out their respective induced alterations. However, treatment with binary mixtures including PCB153 gave rise to an enhanced segregation. Our findings suggest that test agents which mediate their cellular effects via similar mechanisms might result in inhibition within a binary mixture whereas independently acting agents could exacerbate induced alterations in overall cell status.

Identification of Hydroxylated Octa- and Nona-Bromodiphenyl Ethers in Human Serum from Electronic Waste Dismantling Workers

Previous studies have reported high serum concentrations of polybrominated diphenyl ethers, especially decabromodiphenyl ether (BDE-209), in the residents of an electronic waste (e-waste) dismantling site in Guiyu town, South China. In the present study, human serum samples in this region were collected and pooled for the identification of hydroxylated diphenyl ethers (OH-PBDEs). Three OH-PBDEs, including two hydroxylated octabromodiphenyl ethers (OH-octaBDEs, 6-OH-BDE196 and 6-OH-BDE199) and one hydroxylated nonabromodiphenyl ether (OH-nonaBDE, 6'-OH-BDE206), were first structurally identified. Identification was done by coeluting a mixture of synthetic authentic standards with the methylated OH-PBDEs from the pooled samples using two gas chromatography columns with different polarities. The results were supported by full scan mass spectrometric data in electron capture negative ionization mode. All three OH-PBDE metabolites had hydroxy groups substituted in the ortho position. These results indicate that hydroxylated higher brominated diphenyl ethers such as OH-octaBDEs and OH-nonaBDEs can accumulate in human blood. The results suggest that higher brominated diphenyl ethers could be oxidatively metabolized into OH-PBDEs in humans. Because low brominated OH-PBDEs can also be detected in abiotic media, further investigations are needed to determine the presence of higher brominated OH-PBDEs in the environment in this region.

Characterization of an abundant and novel methyl- and methoxy-substituted brominated diphenyl ether isolated from whale blubber

A previously unidentified yet abundant substituted polybrominated diphenyl ether (PBDE) was isolated from a northern bottlenose whale ( Hyperoodon ampullatus) found dead in the Skagerrak, North Sea. A combination of gas chromatography, high and low resolution mass spectrometry and nuclear magnetic resonance spectroscopy (NMR) ( 1H, 1H– 1H and 1H– 13C) after isolation with preparative capillary gas chromatography (PCGC) lead to the identification of the unknown substance as 6-MeO-5-Me-2,2′,3,4′-tetrabromo diphenyl ether (6-MeO-5-Me-BDE42). To our knowledge this is only the second time PCGC has been used to isolate individual organohalogen compounds present in trace amounts for identification with NMR. The concentration of this novel bioaccumulated compound was estimated to be about 100 ng g −1 lipid, which was 2.5 times higher compared with the most abundant MeO-PBDE congeners.

Zinc dust-mediated reductive degradation of decabromodiphenyl ether

Zinc dust serves as a reducing agent in the presence of ammonium formate and NaOH, and is highly effective for the hydrodebromination of decabromodiphenyl ether to give diphenyl ether and the less brominated diphenyl ethers.

Development of a noncompetitive phage anti-immunocomplex assay for brominated diphenyl ether 47

We present a new application of the noncompetitive phage anti-immunocomplex assay (PHAIA) by converting an existing competitive assay to a versatile noncompetitive sandwich-type format using immunocomplex binding phage-borne peptides to detect the brominated flame retardant, brominated diphenyl ether 47 (BDE 47). Three phage-displayed 9-mer disulfide-constrained peptides that recognize the BDE 47–polyclonal antibody immunocomplex were isolated. The resulting PHAIAs showed variable sensitivities, and the most sensitive peptide had a dose–response curve with an SC 50 (concentration of analyte producing 50% saturation of the signal) of 0.7 ng/ml BDE 47 and a linear range of 0.3–2 ng/ml, which was nearly identical to the best heterologous competitive format (IC 50 of 1.8 ng/ml, linear range of 0.4–8.5/ml). However, the PHAIA was 1400-fold better than homologous competitive assay. The validation of the PHAIA with extracts of house furniture foam as well as human and calf sera spiked with BDE 47 showed overall recovery of 80–113%. The PHAIA was adapted to a dipstick format (limit of detection of 3.0 ng/ml), and a blind test with six random extracts of local house furniture foams showed that the results of the PHAIA and dipstick assay were consistent, giving the same positive and negative detection.

Concentrations and profiles of brominated diphenyl ethers (BDEs) in Baltic and Atlantic herring

The total concentrations of BDEs in Baltic herring, caught in different years (2002–08) from various areas of the Baltic, and in Atlantic herring (2006) can be reasonably well described by a single concentration vs weight relationship. Samples collected a few years earlier and analysed by others show a slightly different relationship. This indicates that the weight of the fish is an important factor determining the level of contamination and that the contamination apparently did not increase between 1999 and 2008. However, two Baltic herring samples collected in 2007 contained, for reasons unknown, very high concentrations of BDE 209. The BDE profiles (concentrations scaled to a sum of 100) varied a great deal. It is impossible to determine how much of this variation is real and how much is caused by errors in the analyses. The concentration of the BDE 75 was much higher in the Atlantic than in the Baltic herring. Even after taking this into consideration, however, the BDE profile in Atlantic herring is different from the BDE profiles in Baltic herring.

Determination of brominated diphenyl ethers (from mono- to hexa- congeners) in indoor dust by pressurised liquid extraction with in-cell clean-up and gas chromatography–mass spectrometry

This study presents a selective pressurised liquid extraction (PLE) and gas chromatography-mass spectrometry/mass spectrometry method for the determination of brominated diphenyl ethers (BDEs) in indoor dust. Selective PLE consisted of the addition of Florisil mixed with the sample in order to perform an in-cell clean-up. This approach provided a cleaner and almost colourless extract, ready to be injected in the gas chromatograph. The PLE conditions were studied using an experimental design, firstly a 4 x 3 x 2 multifactor categorical design to screen sorbent, solvent and temperature and then a central composite design to optimise sorbent mass, temperature and time. Finally, the number of extraction cycles was studied. The selected conditions were 4 g of Florisil all mixed with the sample and no additional clean-up sorbent layer, 1:1 n-hexane-dichloromethane, 60% flush volume, 40 degrees C, 1,500 psi, 2-min static time and one cycle. The proposed method allowed accurate determination of BDEs, with recovery values between 82% and 101% and detection limits between 0.06 and 0.24 ng g(-1). It also has advantages over other existing methods in terms of simplicity, automation, analysis time and solvent consumption.

Evaluation of the state-of-the-art measurement capabilities for selected PBDEs and decaBB in plastic by the international intercomparison CCQM-P114

An international intercomparison involving eight national metrology institutes (NMIs) was conducted to establish their current measurement capabilities for determining five selected congeners from the brominated flame retardant classes polybrominated diphenyl ethers and polybrominated biphenyls. A candidate reference material consisting of polypropylene fortified with technical mixtures of penta-, octa- and decabromo diphenyl ether and decabromo biphenyl, which was thoroughly assessed for material homogeneity and stability, was used as study material. The analytical procedures applied by the participants differed with regard to sample pre-treatment, extraction, clean-up, employed calibrants and type of calibration procedure as well as regarding analytical methods used for separation, identification and quantification of the flame retardant congeners (gas chromatography coupled to an electron capture detector (GC-ECD), gas chromatography-mass spectrometry in the electron ionisation mode (GC-EI-MS), gas chromatography-mass spectrometry in the electron capture negative ionisation mode (GC-ECNI-MS), and liquid chromatography-inductive coupled plasma-mass spectrometry (LC-ICP-MS)). The laboratory means agreed well with relative standard deviations of the mean of means of 1.9%, 4.8%, 5.5% and 5.4% for brominated diphenyl ether (BDE) 47, 183 and 209 and for the brominated biphenyl (BB) congener 209, respectively. For BDE 206, a relative standard deviation of 28.5% was obtained. For all five congeners, within-laboratory relative standard deviations of six measurements obtained under intermediate precision conditions were between 1% and 10%, and reported expanded measurements uncertainties typically ranged from 4% to 10% (8% to 14% for BDE 206). Furthermore, the results are in good agreement with those obtained in the characterization exercise for determining certified values for the flame retardant congeners in the same material. The results demonstrate the state-of-the-art measurement capabilities of NMIs for quantifying representative BDE congeners and BB 209 in a polymer. The outcome of this intercomparison (pilot study) in conjunction with possible improvements for employing exclusively calibrants with thoroughly assessed purity suggests that a key comparison aiming at underpinning calibration and measurement capability (CMC) claims of NMIs can be conducted.

Comparative Cytotoxicity and Intracellular Accumulation of Five Polybrominated Diphenyl Ether Congeners in Mouse Cerebellar Granule Neurons

Polybrominated diphenyl ethers (PBDEs), a group of flame retardants comprising 209 congeners, have become widespread environmental pollutants. High levels of PBDEs have been detected in human tissues, particularly in North America, and body burden is especially high in infants and toddlers because of exposure through breast milk and house dust. Increasing evidence, provided by animal studies, suggests that PBDEs are developmental neurotoxicants, although the underlying mechanisms are still unknown. Various PBDEs have been reported to cause oxidative stress and to induce apoptotic cell death in several cell types. In the present study, we investigated the comparative neurotoxicity in mouse cerebellar granule neurons of five brominated diphenyl ether (BDE) congeners, chosen among the most commonly found at the highest levels in human tissues. All BDE congener tested (BDE-47, BDE-99, BDE-100, BDE-153, and BDE-209) decreased cell viability and induced apoptotic cell death, which was prevented by antioxidants. They also caused oxidative stress, as indicated by an increase in reactive oxygen species and in lipid peroxidation. For all end points measured, the potency ranking of the congeners was BDE-100 > BDE-47 > BDE-99 > BDE-153 >> BDE-209. Measurement of BDE congener levels in neurons after exposure to different concentrations showed a significant accumulation in cells, which followed the same relative ranking. The findings suggest that all BDE congeners tested exhibit the same general mode of action (induction of oxidative stress-mediated apoptosis) and that the ability of each isomer to elicit such effects is dependent upon their accumulation in neurons, particularly in the microsomal fraction and the mitochondria.

Recombinant Albumin and Transthyretin Transport Proteins from Two Gull Species and Human: Chlorinated and Brominated Contaminant Binding and Thyroid Hormones

Environmentally relevant concentrations of selected polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) flame retardant congeners and their hydroxylated (OH) and methoxylated (MeO) analogues that can perturb thyroid hormone-dependent processes were comparatively examined with respect to competitive binding with thyroxine (T(4)) and 3,5,3'-triiodothyronine (T(3)) thyroid hormones (THs) on recombinant human and gull albumin and transthyretin transport proteins. The liver tissue was from glaucous gulls (Larus hyperboreus) from Norway and herring gulls (Larus argentatus) from the Great Lakes of North America. We isolated, cloned, sequenced, purified, and expressed the cDNA (cDNA) of albumin from liver of herring and glaucous gull. Albumin amino acid sequences were identical for both gull species. Concentration-dependent, competitive binding curves were generated for T(4) and T(3) binding alone and for selected substrates using gull and human recombinant albumin (recALB). Human recALB had high preference for T(4) relative to T(3), whereas it was reversed for gull recALB. Binding assays with recALB and recTTR gull proteins showed that relative to 2,2',4,4'-tetrabromoDE (BDE-47) and 2,2',3,4',5,5',6-heptaCB (CB-187) and the MeO-substituted (4-MeO-CB187 and 6-MeO-BDE47) analogues, 4-OH-CB187, 6-OH-BDE47, and 4'-OH-BDE49 had the greatest binding affinity and potency, and that competitive binding was greater for T(3) relative to T(4). These results indicate that xenobiotic ligand binding to human ALB or TTR cannot be used as a surrogate for gull binding interactions. The combination of TH-like brominated diphenyl ether backbone (relative to the chlorinated biphenyl backbone), and the presence of OH-group produced a more effective competitive ligand on human and gull recALB and recTTR relative to both T(3) and T(4). This suggests the possibility that OH-substituted organohalogen contaminants may be an exposure concern to the thyroid system in free-ranging gulls as well as for humans.

Relationships Between Brominated Flame Retardant Concentrations in House Dust and Serum Hormone Levels in Men

ISEE-0454 Background and Objective: Human exposure to brominated flame retardants (BFRs) is widespread, occurring primarily through diet or contact with indoor dust. There is laboratory evidence of endocrine disruption in animals following exposure to BFRs, but human studies are limited. In this preliminary investigation, we examined the association between BFR levels in house dust and hormone levels in men. Methods: We measured serum hormone levels and BFR concentrations in participant vacuum bag dust from 38 men recruited through a Massachusetts infertility clinic as part of an ongoing study of environmental exposures and male reproductive health. Statistical methods included the calculation of Spearman correlations among BFRs and between BFRs and serum hormone levels, and multivariable linear regression. Results: There were strong correlations (r ≥ 0.80, P < 0.05) among dust concentrations of brominated diphenyl ether (BDE) congener groups with a similar degree of bromination. Positive correlations were found (P ≤ 0.05) between several BDE congeners and serum levels of prolactin and total T3, and between bistribromophenoxyethane and total T3. Hexabromocyclododecane was positively correlated with free androgen index (FAI) (r = 0.46, P = 0.004). Most of these relationships remained statistically significant or suggestive in multivariate linear regression models adjusted for age and BMI. There was a suggestive inverse association between BDE209 and testosterone when adjusting for age, BMI, and serum sex hormone binding globulin (SHBG) (P = 0.09). When dust concentrations of BDE99 were combined with results from a previous analysis of 24 men from the same cohort (n = 62), regression models adjusted for age, BMI, and dust analytical method showed positive relationships between BDE99 and serum estradiol, free T4, and SHBG (P < 0.05). Inverse associations between BDE99 and follicle stimulating hormone (P < 0.05) and FAI (P = 0.11) were also found. Conclusion: This study provides evidence of altered hormone levels in relation to BFR exposure and that house dust may be an important source of human BFR exposure.

Human Liver Microsome-Mediated Metabolism of Brominated Diphenyl Ethers 47, 99, and 153 and Identification of Their Major Metabolites

While the metabolism and excretion of polybrominated diphenyl ethers (PBDEs) have been reported in rodents, PBDE metabolism in humans has only recently been investigated. In this present study, individual human liver microsomes were incubated for 120 min with radiolabeled and nonradiolabeled BDE 47, 99, or 153 to determine their relative degrees of metabolism and to identify the structures of metabolites formed. Radiolabeled samples were analyzed using high-performance liquid chromatography/radiochemical detection, while nonradiolabeled samples were analyzed with and without derivatization using gas chromatography/mass spectrometry. Results from radiolabeled incubations demonstrated that human liver microsomes metabolized BDEs 47 and 99 but not BDE 153. Differences in the extent of BDE metabolism by the three individual liver specimens used in the study were observed. BDE 47 metabolized to a dihydroxylated BDE 47 and 2,4-dibromophenol, while BDE 99 metabolized to a dihydroxylated BDE 99, 2,4,5-tribromophenol and 1,3-dibromobenzene. This study showed that BDEs 47 and 99 are metabolized by human liver microsomes with relatively large interindividual differences. Results of this study could provide one explanation for the high bioaccumulation rate of BDE 153 in humans.

Ultra-trace determination of Persistent Organic Pollutants in Arctic ice using stir bar sorptive extraction and gas chromatography coupled to mass spectrometry

This study presents the optimization and application of an analytical method based on the use of stir bar sorptive extraction (SBSE) gas chromatography coupled to mass spectrometry (GC–MS) for the ultra-trace analysis of POPs (Persistent Organic Pollutants) in Arctic ice. In a first step, the mass-spectrometry conditions were optimized to quantify 48 compounds (polycyclic aromatic hydrocarbons, brominated diphenyl ethers, chlorinated biphenyls, and organochlorinated pesticides) at the low pg/L level. In a second step, the performance of this analytical method was evaluated to determine POPs in Arctic cores collected during an oceanographic campaign. Using a calibration range from 1 to 1800 pg/L and by adjusting acquisition parameters, limits of detection at the 0.1–99 and 102–891 pg/L for organohalogenated compounds and polycyclic aromatic hydrocarbons, respectively, were obtained by extracting 200 mL of unfiltered ice water. α-hexachlorocyclohexane, DDTs, chlorinated biphenyl congeners 28, 101 and 118 and brominated diphenyl ethers congeners 47 and 99 were detected in ice cores at levels between 0.5 to 258 pg/L. We emphasise the advantages and disadvantages of in situ SBSE in comparison with traditional extraction techniques used to analyze POPs in ice.

Polybrominated diphenyl ethers and their hydroxylated analogs in plasma of bottlenose dolphins (Tursiops truncatus) from the United States east coast

Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs (OH-PBDEs) were determined in plasma of free-ranging bottlenose dolphins (Tursiops truncatus) from Charleston (CHS), South Carolina, and the Indian River Lagoon (IRL), Florida, U.S.A. Significantly lower sums (sigma) of PBDE concentrations (sum of 12 congeners) were found in animals from the IRL (arithmetic mean, 5.45 +/- 4.63 ng/g wet wt) compared with those from CHS (30 +/- 40 ng/g wet wt). Brominated diphenyl ether (BDE)-47 was the predominant PBDE in dolphins from the IRL (50% of the sigma PBDEs) and CHS (58%). The sigma PBDE concentrations in plasma of dolphins were negatively correlated with age at both locations. Fifteen and sixteen individual OH-PBDE congeners could be quantified in plasma of dolphins from IRL and CHS, respectively. Similar to sigma PBDE, mean sigma OH-PBDE concentrations were significantly higher in plasma of dolphins at CHS (1150 +/- 708 pg/g wet wt) compared with those at IRL (624 +/- 393 pg/g wet wt). The predominant congener at both locations was 6-OH-PBDE-47 (IRL, 384 +/- 319 pg/g wet wt; CHS, 541 +/- 344 pg/g wet wt), representing 61.5% of total sigma OH-PBDE at IRL and 47.0% at CHS. Concentrations of sigma OH-PBDEs were weakly negatively correlated with age in dolphins from both locations (p < 0.05; IRL, r2 = 0.048; CHS, r2 = 0.021). In addition to the OH-PBDE congeners identified with technical standards, eight and four unidentified OH-PBDEs were detected and quantified, respectively, in animals from CHS (sum of unidentified OH-PBDEs = 1.35 +/- 0.90 pg/g wet wt) and IRL (0.73 +/- 0.40 pg/g wet wt). Results of the present study suggest that, unlike OH-PCBs, OH-PBDEs in bottlenose dolphins are minor products in plasma relative to sigma PBDEs and a significant proportion may be a consequence of the dietary uptake of naturally produced methoxylated- and OH-PBDEs.

Quantitative structure – Photodegradation relationships of polybrominated diphenyl ethers, phenoxyphenols and selected organochlorines

Among other developments, the technological revolution has lead to introduction of new chemicals to better serve in instruments and materials. The consequences of the extensive increase in use of new chemicals can be detected in the environment world wide, i.e. in wildlife and humans. To ensure this problem to be minimised in the future, new chemicals need to be subjected to predictive assessments before commercialised. To facilitate screening, qualitative structure–activity relationships, quantitative structure–activity relationships may be applied to describe reactivity of chemicals. Physico-chemical properties of chemicals such as partition coefficients and half-lives for the various environmental compartments are essential input data in multimedia environmental fate models. In this study we examine how structural characteristics can quantitatively describe laboratory determined photolytic half-lives of halogenated compounds of different classes, such as polybrominated diphenyl ethers (PBDEs), hydroxylated brominated diphenyl ethers (OH-PBDEs), and other organohalogens. A total of 30 chemicals with experimentally measured half-lives are used. Results reveal that the most important descriptors for describing the half-lives of the brominated compounds are the energy gap (GAP-1) between HOMO-1 and LUMO, the lowest partial charge on a halogen atom (Qhal−), topological polar surface area (TPSA), the atom with highest radical superdelocalizability (Rad-super+) and LUMO density (LUMO+).

Unusual hepta‐ and octabrominated diphenyl ethers and nonabrominated diphenyl ether profile in California, USA, peregrine falcons (Falco peregrinus): More evidence for brominated diphenyl ether‐209 debromination

High (maximum of 4.1 ppm lipid weight) levels of BDE-209 and other higher brominated diphenyl ethers (BDEs) found in California, USA, peregrine falcon (Falco peregrinus) eggs (n = 95) provided an opportunity to examine homolog profiles of nona-, octa-, and hepta-BDEs as possible evidence for biological debromination of BDE-209. We found two congeners in eggs, an unidentified hepta-BDE (BDE-heptaUNK) and BDE-202 (octa-BDE) that are not present in commercial mixtures. In addition, BDE-208 (nona-BDE) was present at much higher (10-fold) proportions in eggs than in commercial mixtures. To examine whether these unusual homolog patterns arose from assimilation of environmentally degraded BDE commercial mixtures, we compared nona-hepta-BDE homolog profiles of peregrine falcon eggs with those of weathered BDEs present in various abiotic matrices (sludge, sediment, and dusts). We found the profiles differed significantly: BDE-207 was the major nona-BDE in eggs, whereas BDE-206 was the major nona-BDE in abiotic matrices. Thus, the evidence for the biological debromination of BDE-209 in peregrine falcons is twofold: Eggs have two congeners (BDE-202 and -heptaUNK) that are not reported for any commercial mixtures nor in the abiotic matrices examined thus far, and eggs have higher-brominated BDE homolog patterns that are different from those found in commercial mixtures or environmental matrices.

Origin of Hydroxylated Brominated Diphenyl Ethers: Natural Compounds or Man-Made Flame Retardants?

Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants. The structurally related hydroxylated PBDEs (OH-PBDEs) and methoxylated PBDEs (MeO-PBDEs) occur in precipitation, surface water, wildlife, and humans. The formation of OH-PBDEs in wildlife and humans is of considerable concern due to their greater toxicities relative to PBDEs and MeO-PBDEs. Research to date suggests that OH-PBDEs are formed by hydroxylation of PBDEs, and MeO-PBDEs are then formed by methylation of the OH-PBDEs. Here we show significant metabolic production of OH-PBDEs from MeO-PBDEs while hydroxylation of synthetic PBDEs to OH-PBDEs was negligible. Concentrations of PBDEs, OH-PBDEs, and MeO-PBDEs were analyzed in tuna, albatross, and polar bears collected from marine environments worldwide, and we found a closer relationship between OH-PBDEs and MeO-PBDEs than had been previously reported. Furthermore, for the first time the metabolic relationships between PBDEs, OH-PBDEs, and MeO-PBDEs were elucidated in vitro using rainbow trout, chicken, and rat microsomes. We propose the production of OH-PBDEs from naturally occurring MeO-PBDEs as a previously unidentified mechanism that could be an important contributor for the occurrence of OH-PBDEs found in wildlife from remote areas. Our results suggest that risk assessment paradigms for PBDEs and their metabolites need reevaluation and that human exposure to MeO-PBDEs that occur naturally in marine organisms should be considered.

Ichthyotoxic brominated diphenyl ethers from a mixed assemblage of a red alga and cyanobacterium: Structure clarification and biological properties

Primary fractions from the extract of a tropical red alga mixed with filamentous cyanobacteria, collected from Papua New Guinea, were active in a neurotoxicity assay. Bioassay-guided isolation led to two natural products ( 1, 2) with relatively potent calcium ion influx properties. The more prevalent of the neurotoxic compounds ( 1) was characterized by extensive NMR, mass spectrometry, and X-ray crystallography, and shown to be identical to a polybrominated diphenyl ether metabolite present in the literature, but reported with different NMR properties. To clarify this anomalous result, we synthesized a candidate isomeric polybrominated diphenyl ether ( 3), but this clearly had different NMR shifts than the reported compound. We conclude that the original isolate of 3,4,5-tribromo-2-(2,4-dibromophenoxy)phenol was contaminated with a minor compound, giving rise to the observed anomalous NMR shifts. The second and less abundant natural product ( 2) isolated in this study was a more highly brominated species. All three compounds showed a low micromolar ability to increase intracellular calcium ion concentrations in mouse neocortical neurons as well as toxicity to zebrafish. Because polybrominated diphenyl ethers have both natural as well as anthropomorphic origins, and accumulate in marine organisms at higher trophic level (mammals, fish, birds), these neurotoxic properties are of environmental significance and concern.

Analysis and occurrence of emerging brominated flame retardants in the Llobregat River basin

Summary In response to increasing international regulations on brominated flame retardants (BFR) formulations, alternative additive flame retardants for achieving commercial product fire safety standards are being developed and used. Some of these non-BDE (brominated diphenyl ethers) BFRs are pentabromoethylbenzene (PBEB), hexabromobenzene (hexaBBz), and decabromodiphenylethane (deBDethane). The present study investigated the occurrence of these emerging BFRs, together with 38 BDE congeners (from di- to deca-BDE) in sediments sampled from different points along Llobregat basin (Spain) in three different sampling campaigns between 2005 and 2006. Emerging BFRs were detected in all sediment samples analyzed, at concentrations ranging from 3.1 to 9.6 ng/g for PBEB, from 0.4 to 2.4 ng/g for hexaBBz and from 4.8 to 23 ng/g for deBDethane. These levels are lower than concentrations obtained for PBDEs (from nd to 82 ng/g).

Anaerobic transformation of a technical pentabromo diphenyl ether product using superreduced vitamin B12

Technical pentabromo diphenyl ether (DE-71) was anaerobically transformed using superreduced cyanocobalamin (vitamin B12). The principal pathway was identified to be reductive debromination. As a consequence, the proportion of higher brominated homologues decreased in favor of the lower brominated diphenyl ethers (BDEs) while the molar amount of BDE congeners was virtually constant throughout the experiment. As an example, the ratios of BDE 99/BDE 47 was >1 at the start, ∼1 after 1 week, and <1 after 2 weeks. A further feature identified was the alternating removal of bromine atoms from the two rings when two or more Br were substituted by hydrogen. BDE 49 and BDE 66 proved to be good indicators for the reductive debromination of both DE-71 and DE-79. Hence, a thorough study of BDE 49 and BDE 66 might be helpful to solve the question whether high amounts of key-PBDEs in technical pentabromo diphenyl ether in the environment originate from such sources or are debromination products of higher BDEs.