In Vitro antiandrogenicity of PBDEs, HBCD, TBP and hydroxylated and methoxylated PBDEs based on a yeast bioassay
Brominated flame retardants (BFRs) are chemicals used in all kinds of materials for electronic and daily apparatuses to reduce fire risks. These compounds act in the gas phase of the fire by reacting with free radicals generated during combustion, thus terminating the reaction. From an environmental point of view, BFRs have become an increasingly important group of organohalogen compounds, which include among others polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCD) isomers. Global production of PBDEs alone was about 40,000 tons in 2001. PBDEs can be divided into three major commercial mixtures: Penta-, Octa- and Deca-BDEs. The first two have been recently banned, through voluntary actions by industry, in Europe and will be banned in the near future also in North America. PBDEs have been found in abiotic and biotic environments. They are generally lipophilic, persistent and thus have the potential to bioaccumulate and biomagnify. In the 1970s and 1980s, a substantial increase in PBDE concentrations for example in mother's milk was observed. However, a slight decrease in environmental samples during the last 5¿8 years in Northern Europe has been observed, probably due to the ban of the Penta- and Octa-BDE mixtures. PBDE metabolites, mainly tetrabromo- and pentabromo-methoxylated PBDEs (CH3O-PBDEs) and hydroxylated (OH-PBDEs), have also been detected in the blood and to a lesser extent in adipose and liver tissues of a limited number of fish, bird, and mammalian species. Some of these PBDE metabolites have also been detected in human blood. A number of OH-PBDEs have previously been isolated and structurally identified as natural compounds in marine sponges and in ascidians (tunicates). All naturally occuring OH-PBDEs in these marine organisms have a hydroxyl group at the ortho position relative to the ether bond, and are exemplified by 6-OH-BDE47 and 2¿-OH-BDE68. In vitro studies have shown how some of these OH-PBDEs can bind competitively to thyroid hormone transport proteins such as transthyretin (TTR). Further, some OH-PBDEs may cause estrogenic effects in vitro. Antiandrogenic effects have been shown previously in vitro for some of the BFRs, especially PBDEs, using the AR-CALUX reporter gene system. In some cases, the potency was higher than for natural ligands. Using the human adrenocortical carcinoma cell line (H295R), some of the PBDE derivatives were shown to significantly inhibit CYP19 (aromatase) and CYP17 activity, which are key enzymes in steroidogenesis. However, to some extent, these inhibitory effects were due to cytotoxicity. In order to establish and study the possible effects of BFRs and PBDE metabolites on the androgen receptor (AR), a new highly specific yeast androgen bioassay was used. Different controls and test compounds were tested on both their potential agonistic as well as their antagonistic potency.
| Main Authors: | , , , , |
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| Format: | Article in monograph or in proceedings biblioteca |
| Language: | English |
| Subjects: | Life Science, |
| Online Access: | https://research.wur.nl/en/publications/in-vitro-antiandrogenicity-of-pbdes-hbcd-tbp-and-hydroxylated-and |
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