In vitro biotransformatie van organohalogeenverbindingen in zeezoogdieren en vogels. Mogelijke gevolgen voor bioaccumulatie en genotoxiciteit: 3. Gebromeerde vlamvertragers (polybroom difenylethers en polybroom bifenylen)
Boon, J.P.; Greve, M.J.; Bouma, J.; de Boer, M.K.; Lewis, W.E.; Klamer, H.J.C.; Pastor, D.; Wester, E.; de Boer, J. (1997). In vitro biotransformatie van organohalogeenverbindingen in zeezoogdieren en vogels. Mogelijke gevolgen voor bioaccumulatie en genotoxiciteit: 3. Gebromeerde vlamvertragers (polybroom difenylethers en polybroom bifenylen). BEON Rapport = BEON-report, 97(6). RIKZ: Den Haag. 46 pp.
Part of: BEON Rapport = BEON-report. Programma Bureau BEON: Den Haag. ISSN 0924-6576
Since little is known about the persistence to biotransformation by the cytochrome P-450 system of the brominated flame retardants polybrominated diphenyl ethers (PBDEs) and polybrominated biphenyls (PBBs), an existing in-vitrobioassay was adapted in order to investigate these characteristics in sample of marine mammals and sea birds. Hepatic microsomes of harbour seal (Phoca vitulina), whitebeaked dolphin (Lagenorhynchus albirostirs), sperm whale (Physeter macrocephalus), and eider duck (Somateria mollissima) were incubated with standard PBDE and PBB mixtures. The microsomal preparations were incubated wiht a standard PBDE mixture, containing 2,4,2',4'-tetra, 2,4,5,2',4'-penta and 2,3,4,5,6,2',3',4',5',6'-decabromodiphenyl ether. Assays to which NADPH was added as an electron source allowing for the occurrence of biotransformation were compared to reference samples without NADPH. Three metabolisable chlorobiphenyl congeners (CB-26, CB-28 and CB-101) were added as positive controls, whereas CB-153 was added as an internal standard. The positive controls and EROD activity measurements confirmed the abililty of the microsomes to perform cytochrome P-450 mediated biotransformation reactions. All reactions did not show significant biotransformation of the BDE congeners. Although PBDEs seem to have affinity to the same biological receptors as the PCBs, they did not inhibit metabolism of the CB congeners used as positive control. In case of the PBBs, the microsomes of all three marine mammals were able to biotransform the BB-15, in contrast to the microsomes of an eider duck. BB-15 (4,4'-dibromobiphenyl) contains vicinal hydrogen atoms exclusively at the ortho-meta positions. All four test animals in this study were incapable of metabolizing the remaining BB congeners with vicinal H atoms (BB-155, BB-153 and BB-169). The apparent persistence of both classes of brominated flame retardants was clearly reflected in fact that environmental residues of compounds belonging to both classes of flame retardants were found in all samples analyzed. The PBDE levels were generally more than 50 times higher than those of the PBBs. Since residues were also found in blubber and libber of all three sperm whales investigated, it was concluded that both classes of compounds can considered to be global pollutants, since healthy sperm whales generally stay in deep water and their occurrence in shelf seas is considered to be accidental. The concentrations of the fully brominated congeners decabromodiphenylether or decabromobiphenyl were below the limits of detection. Since these compounds are unlikely to be metabolised by the cytochrome P-450 system, this most likely results from the fact that these molecules are too large to be taken up, or their debromination by other processes in the environment. Both classes of compounds did not show a genotoxic response in the Mutatox® assay. The absence of a direct mutagenicity of these compounds is supported by the existing literature, which also includes experiments with laboratory rodents. However, PBBs and PBDEs can potentiate the carcinogenic properties of other compounds. Since they often occur together with polyaromatic hydrocarbons (PAHs), of which a number of compounds is highly carcinogenic, this may be a highly relevant mechanism in the field situation. In other studies, PBBs were shown to affect reproductive processes and the regulation of steroid and thyroid hormones in laboratory rodents, birds and monkeys. PBDEs affected reproductive processes in fish.
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