| 1. |
- Legradi, Jessica, et al.
(författare)
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Disruption of oxidative phosphorylation (OXPHOS) by hydroxylated polybrominated diphenyl ethers (OH-PBDEs) present in the marine environment
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:24, s. 14703-14711
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are of growing concern, as they have been detected in both humans and wildlife and have been shown to be toxic. Recent studies have indicated that OH-PBDEs can be more toxic than PBDEs, partly due to their ability to disrupt oxidative phosphorylation (OXPHOS), an essential process in energy metabolism. In this study, we determined the OXPHOS disruption potential of 18 OH-PBDE congeners reported in marine wildlife using two in vitro bioassays, namely the classic rat mitochondrial respiration assay, and a mitochrondrial membrane potential assay using zebrafish PAC2 cells. Single OH-PBDE congeners as well as mixtures were tested to study potential additive or synergistic effects. An environmental mixture composed of seven OH-PBDE congeners mimicking the concentrations reported in Baltic blue mussels were also studied. We report that all OH-PBDEs tested were able to disrupt OXPHOS via either protonophoric uncoupling and/or inhibition of the electron transport chain. Additionally we show that OH-PBDEs tested in combinations as found in the environment have the potential to disrupt OXPHOS. Importantly, mixtures of OH-PBDEs may show very strong synergistic effects, stressing the importance of further research on the in vivo impacts of these compounds in the environment
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| 2. |
- Marsh, B. A., et al.
(författare)
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The ISOLDE RILIS pump laser upgrade and the LARIS Laboratory
- 2010
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Ingår i: Hyperfine Interactions. - : Springer Nature. - 0304-3843 .- 1572-9540. ; 196:1-3, s. 129-141
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Tidskriftsartikel (refereegranskat)abstract
- On account of its high efficiency, speed and unmatched selectivity, the Resonance Ionization Laser Ion Source (RILIS) is the preferred method for ionizing the nuclear reaction products at the ISOLDE on-line isotope separator facility. By exploiting the unique electronic energy level 'fingerprint' of a chosen element, the RILIS process of laser step-wise resonance ionization enables an ion beam of high chemical purity to be sent through the mass selective separator magnet. The isobaric purity of a beam of a chosen isotope is therefore greatly increased. The RILIS, comprising of up to three frequency tunable pulsed dye lasers has been upgraded with the installation of a Nd:YAG pump laser as a replacement for the old Copper Vapor Laser (CVL) system. A summary of the current Nd:YAG pumped RILIS performance is given. To accompany the RILIS pump laser upgrade, a new ionization scheme for manganese has been developed at the newly constructed LAser Resonance Ionization Spectroscopy (LARIS) laboratory and successfully applied for on-line RILIS operation. An overview of the LARIS facility is given along with details of the ionization scheme development work for manganese.
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| 3. |
- Montano, Mauricio, et al.
(författare)
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New Approaches to Assess the Transthyretin Binding Capacity of Bioactivated Thyroid Hormone Disruptors
- 2012
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 130:1, s. 94-105
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Tidskriftsartikel (refereegranskat)abstract
- Polychlorinated biphenyls (PCBs) and polybrominated diphenyl-ethers (PBDEs) are metabolized into hydroxylated metabolites (OH-PCBs/PBDEs), which can disrupt the thyroid hormone homeostasis. Binding of these metabolites to transport proteins such as transthyretin (TTR) is an important mechanism of their toxicity. Several methods to quantify the competitive thyroxine (T-4) displacement potency of pure metabolites exist. However, quantification of the potency of in vitro metabolized PCBs and PBDEs has drawbacks related to the coextraction of compounds disturbing the T-4-TTR competitive binding assay. This study identifies and quantifies the major coextractants namely cholesterol, saturated and nonsaturated fatty acids (SFA and NSFA) at levels above 20 nmol per mg equivalent protein following various extraction methods. Their TTR binding potency was analyzed in a downscaled, nonradioactive fluorescence displacement assay. At concentration factors needed for TTR competitive binding, at least 10M of these coextracts is present, whereas individual SFA and NSFA disturb the assay from 0.3M. The effectiveness of the in vitro metabolism and extraction of the model compounds CB 77 and BDE 47 was chemically quantified with a newly developed chromatographic method analyzing silylated derivatives of the OH-metabolites and coextractants. A new method to selectively extract metabolites and limit coextraction of disturbing compounds to less than 5 nmol per mg equivalent protein is presented. It is now possible to make a dose-response curve up to 50% inhibition with bioactivated CB 77 and BDE 47. The toxic potencies of bioactivated persistent organic pollutants (POPs) should be taken into account to prevent serious underestimation of their hazard and risk.
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| 4. |
- Rydén, Andreas, 1981-, et al.
(författare)
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Synthesis and tentative identification of novel polybrominated diphenyl ether metabolites in human blood
- 2012
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 88:10, s. 1227-1234
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxylated polybrominated diphenyl ethers (OH-PDBEs) are exogenous, bioactive compounds that originate, to a large extent, from anthropogenic activities, although they are also naturally produced in the environment. In the present study nine new authentic OH-PBDE reference standards and their corresponding methyl ether derivatives (MeO-PBDEs) were synthesised and characterised by NMR spectroscopy and mass spectrometry. Seven of the authentic reference standards prepared were thereafter tentatively identified in a pooled human blood sample. The tentatively identified OH-PBDEs were 3-hydroxy-2,2',4,4',6-pentabromodiphenyl ether, 3'-hydroxy-2,2',4,4',6-pentabromodiphenyl ether, 3-hydroxy-2,2',4,4',5-pentabromodiphenyl ether, 3-hydroxy-2,2',4,4',5,6'-hexabromodiphenyl ether. 3'-hydroxy-2,2',4,4',5,6'-hexabromodiphenyl ether, 3-hydroxy-2,2',4,4',5,5'-hexabromodiphenyl ether and 4-hydroxy-2,2',3,4',5,5',6-heptabromodiphenyl ether. An additional seven OH-PBDEs were tentatively identified in the pooled human blood sample, of which one OH-PBDE, 4'-hydroxy-2,2',4,5,5'-pentabromodiphenyl ether, has not been identified in human blood before. The identification was performed using gas chromatography-mass spectrometry (GC-MS) recording the bromine ions m/z 79, 81. The tentative identification was supported by the peaks relative retention times (RRTs) compared to authentic references on two GC columns of different polarities for the hexa-, and heptabrominated OH-PBDEs, and three different GC columns for the pentabrominated OH-PBDEs. The OH-PBDE congeners most likely originate from human metabolism of a flame retardant, i.e. polybrominated diphenyl ethers (PBDEs), due to the relatively high concentrations of PBDEs in the same human blood sample and the fact that these PBDEs could form the tentatively identified OH-PBDEs via metabolic direct hydroxylation or via 1,2-shift.
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| 5. |
- Rydén, Andreas, 1981-
(författare)
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Synthesis of organobromines as a tool for their characterisation and environmental occurrence assessment
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Polybrominated diphenyl ethers (PBDEs) have been intensively used as flame retardants (FRs) and have become ubiquitous environmental pollutants. PBDEs form hydroxylated PBDEs (OH-PBDEs) as metabolites. Further, some OH-PBDEs and methoxy-PBDEs (MeO-PBDEs) are natural products. These are all compounds of environmental and health concern and it is therefore important to confirm their identity and to assess their environmental levels and toxicities. Hence, it is vital to obtain authentic reference standards of individual PBDEs and OH/MeO-PBDEs. The thesis main aim was to develop synthesis methods of congener specific PBDEs, OH- and MeO-PBDEs. The second aim was to identify and quantify PBDEs, OH- and MeO-PBDEs in environmental samples. The third was to propose an abbreviation system for FRs.O-Arylation of brominated phenols, using either symmetrical or unsymmetrical brominated diphenyliodonium salts, was selected for synthesis of PBDEs and OH-/MeO-PBDEs. A total of 16 MeO-PBDEs, 11 OH-PBDEs, 1 diMeO-PBDE and 1 EtO-MeO-PBDE were synthesised. Three novel unsymmetrical diaryliodonium triflates were synthesised and used in synthesis. Optimisations were made to construct a reliable general method for congener specific PBDE synthesis, which was used in the synthesis of 8 representative PBDE congeners. The products were generally characterised by electron ionisation mass spectrometry (EIMS) and nuclear magnetic resonance (NMR) spectroscopy.Identification of PBDEs and OH-PBDEs in various matrixes was based on gas chromatographic and mass spectrometric analyses. Fourteen OH-PBDE congeners were identified in a pooled human blood sample. One previously uncharacterised natural PBDE analogue was identified as 6-OH-6’-MeO-BDE-194, and quantified in Swedish blue mussels. PBDE congeners and other BFRs were identified and quantified in workers and dust from a smelter in Sweden.A structured and practical abbreviation system was developed for halogen- and phosphorus containing FRs.
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| 6. |
- Unger, Maria, 1980-, et al.
(författare)
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Characaterization of an abundant and novel methyl- and methoxy-substituted brominated diphenyl ether isolated from whale blubber
- 2010
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 79:4, s. 408-413
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Winnberg, Ulrika, et al.
(författare)
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Novel Octabrominated Phenolic Diphenyl Ether Identified in Blue Mussels from the Swedish West Coast
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:6, s. 3319-3326
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxylated (OH−) and methoxylated (MeO−) polybrominated diphenyl ethers (PBDEs) are compounds present in the marine environment and OH–PBDEs are of toxicological concern and are therefore of interest to monitor in the environment. A phenolic octaBDE was tentatively identified in the phenolic fraction of previously analyzed mussel samples after methylation of the halogenated phenolic compounds (HPCs). The aim of the present study was to confirm the identity of this compound in blue mussels and investigate whether the analyte is diOH– and/or OH–MeO–octaBDE. Two reference standards, 6,6′-dimethoxy-2,2′,3,3′,4,4′,5,5′-octabromodiphenyl ether (6,6′-diMeO–BDE194) and 6-ethoxy-6′-methoxy-2,2′,3,3′,4,4′,5,5′-octabromodiphenyl ether (6-EtO-6′-MeO–BDE194) were prepared via O-arylation of 2,3,4,5-tetrabromo-6-methoxyphenol and 2,3,4,5-tetrabromo-6-ethoxyphenol, respectively, with a novel unsymmetrical diaryliodonium salt, 2,3,4,5-tetrabromo-6-methoxydiphenyliodonium triflate. The GC retention time and GC/MS spectrum of the synthesized 6,6′-diMeO–BDE194 correspond well with the analyte in the methylated phenolic fraction of a mussel extract from a previous study. Structural analysis performed in this study indicate that the synthesized 6,6′-diMeO–BDE194 and 6-EtO-6′-MeO–BDE194 correspond well with 6-hydroxy-6′-methoxy-2,2′,3,3′,4,4′,5,5′-octabromodiphenyl ether (6-OH–6′-MeO–BDE194) after methylation and ethylation, respectively, of the HPCs in the mussel extracts. The compound 6-OH–6′-MeO–BDE194 was identified and quantified in new mussels, sampled in 2012 from two locations on the Swedish west coast, with geometric mean concentrations of 3700 and 410 ng/g fat, respectively.
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