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Methanol-water dissociation constants and relative transthyretin affinities for hydroxylated metabolites of PCB and PBDE congeners
Stockholm University, Faculty of Science, Department of Environmental Chemistry.
Manuscript (Other academic)
URN: urn:nbn:se:su:diva-23339OAI: diva2:191445
Part of urn:nbn:se:su:diva-245Available from: 2004-09-16 Created: 2004-09-16 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Identification and Characterisation of Hydroxylated PCB and PBDE Metabolites in Blood: Congener specific synthesis and analysis
Open this publication in new window or tab >>Identification and Characterisation of Hydroxylated PCB and PBDE Metabolites in Blood: Congener specific synthesis and analysis
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hydroxylated polychlorinated biphenyls (OH-PCBs) are known metabolites of polychlorinated biphenyls (PCBs) in many mammalian, bird and fish species. Among those, certain OH-PCB congeners are strongly localised in the blood compartment of humans and wild animals. This retention is believed to mainly be a consequence of their high affinity to transthyretin (TTR), a thyroid hormone transport protein, as shown by in vitro binding studies. Polybrominated diphenyls ethers (PBDEs), used as flame retardants, are another group of compounds that forms hydroxylated metabolites (OH-PBDEs), which have been shown in rodents and fish. OH-PBDEs, in difference with OH-PCBs, also exist as natural products, produced by e.g. marine sponges. Several OH-PBDE congeners that have been identified in marine environmental samples seem to originate, to major part, from the natural production of these compounds.

An aim of this work was to develop methods and prepare individual OH-PCB congeners for making them available as analytical standards for qualitative identification of OH-PCBs in human blood. Also the issue of OH-PBDE retention in blood after PBDE exposure was addressed in an experimental study. Further, the aim was to characterise selected, individual OH-PCBs and OH-PBDEs by measuring their dissociation constants, octanol water partitioning and affinity for TTR. A study on the kinetics of two environmental abundant OH-PCBs, 4-OH-CB107 and 4-OH-CB187 was performed in the rat.

About 50 OH-PCB congeners, analysed as their corresponding methyl derivatives, were detected in a pooled blood sample from Swedish males. Thirty-eight OH-PCBs were structurally identified by comparison with 60 authentic individual MeO-PCB standards. Twenty of the MeO-PCB standards were prepared for the identification work. A method has been developed for preparation of a critical intermediate for synthesis of meta-OH substituted OH-PCBs. The calculated plasma half-lives of 4-OH-CB107 and 4-OH-CB187 in rat were shown to be 3.8 days and 15 days, respectively. Dissociation constants for selected OH-PCBs and OH-PBDEs were determined in a methanol/water mixture and psKa values ranged from 5.1 to 7.3, with lower psKa values for the OH-PCBs than the OH-PBDEs. All tested compounds in the TTR in vitro assay showed higher affinity towards TTR than the natural ligand, thyroxine, except for 4-OH-CB199 and 6-OH-BDE47. Sixteen OH-PBDE and two diOH-PBDE metabolites were detected in the plasma of rats after exposure of seven PBDE congeners which of four OH-tetraBDEs were structurally identified. The OH-PBDE metabolites were entirely dominated by meta- and para-substitution of the hydroxy group. The results indicate that OH-PBDE congeners have the ability to be retained in rat blood.

Place, publisher, year, edition, pages
Stockholm: Institutionen för miljökemi, 2004. 48 p.
National Category
Environmental Sciences
urn:nbn:se:su:diva-245 (URN)91-7265-946-7 (ISBN)
Public defence
2004-10-08, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00
Available from: 2004-09-16 Created: 2004-09-16Bibliographically approved

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