title: Estrogenic and androgenic activities of TBBA and TBMEPH, metabolites of novel brominated flame retardants, and selected bisphenols, using the XenoScreen XL YES/YAS assay.
abstract: The present study investigated and compared the estrogenic and androgenic activities of the three different classes of environmental pollutants and their metabolites using the XenoScreen XL YES/YAS assay, which has advantages compared with the original YES/YAS protocol. Contrary to the parent brominated flame retardants TBB and TBPH, which demonstrated no or very weak (anti)estrogenic or (anti)androgenic activities, their metabolites, TBBA and TBMEPH, exhibited anti-estrogenic (IC50 for TBBA=31.75 μM and IC50 for TBMEPH=0.265 μM) and anti-androgenic (IC50 for TBBA=73.95 μM and IC50 for TBMEPH=2.92 μM) activities. These results reveal that metabolism can enhance the anti-estrogenic and anti-androgenic effects of these two novel brominated flame retardants. Based on the activities of BPAF, BPF, BPA and MBP, we can conclude that the XenoScreen XL YES/YAS assay gives comparable results to the (anti)estrogenic or (anti)androgenic assays that are reported in the literature. For BPA, it was confirmed previously that the metabolite formed after an ipso-reaction (hydroxycumyl alcohol) exhibited higher estrogenic activity compared with the parent BPA, but this was not confirmed for BPAF and BPF ipso-metabolites, which were not active in the XenoScreen YES/YAS assay. Among the substituted BPA analogues, bis-GMA exhibited weak anti-estrogenic activity, BADGE demonstrated weak anti-estrogenic and anti-androgenic activities (IC50=13.73 μM), and the hydrolysed product BADGE·2H2O demonstrated no (anti)estrogenic or (anti)androgenic activities.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Anja
authors.initials: A
authors.lastname: Fic
authors.affiliation: Department for Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, Ljubljana, Slovenia.
authors.forename: Bojana
authors.initials: B
authors.lastname: Žegura
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Darja
authors.initials: D
authors.lastname: Gramec
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia. Electronic address: lucija.peterlinmasic@ffa.uni-lj.si.
authors.forename: Lucija Peterlin
authors.initials: LP
authors.lastname: Mašič
mesh_terms: D000726:Androgen Antagonists / Q000378:metabolism / Q000633:toxicity; D001681:Biological Assay / Q000379:methods*; D001970:Bromobenzoates / Q000378:metabolism / Q000633:toxicity*; D002264:Carboxylic Acids / Q000378:metabolism; D052244:Endocrine Disruptors / Q000378:metabolism*; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity; D004965:Estrogen Antagonists / Q000378:metabolism / Q000633:toxicity; D005411:Flame Retardants / Q000378:metabolism*; D055768:Halogenated Diphenyl Ethers / Q000378:metabolism / Q000633:toxicity*; D010636:Phenols / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000187:drug effects*
chemical_list: C544268:2-ethylhexyltetrabromobenzoate; D000726:Androgen Antagonists; D001970:Bromobenzoates; D002264:Carboxylic Acids; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004965:Estrogen Antagonists; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D010636:Phenols
keywords: Bisphenols; Brominated flame retardants; Endocrine disrupting chemicals; Metabolites; YES/YAS assay