Some flame retardants and the antimicrobials triclosan and triclocarban enhance the androgenic activity in vitro

Contaminants including flame retardants antimicrobial agents and phthalates occurring as residues in human tissues were associated with altered endocrine function In our study we analysed the flame retardants tetrabromobisphenol A (TBBPA) hexabromocyclodecane (HBCD) penta-bromodiphenylether (BDE-100) and hexa-BDE (BDE-155) the antimicrobial compounds triclosan (TCS) and triclocarban (TCC) and eight phthalates for their androgenic and antiandrogenic activity in vitro in the MDA-kb2 cell line No or only weak androgenic activity was observed for all the tested compounds TBBPA showed weak antiandrogenic activity which was demonstrated for the first time The flame retardants HBCD BDE 100 and BDE-155 enhanced the dihydrotestosterone dependent activation of androgen receptor-responsive gene expression but exhibited little or no agonistic activity The enhancement reached 150% which was similar to the antimicrobials (TCS up to 180% and TCC up to 130%) This enhancement of androgenic activity represents a novel mode of action of the endocrine activity of flame retardants In contrast most phthalates showed antiandrogenic activity Butylbenzyl phthalate (BBP) dibutyl phthalate (DBP) and diethyl phthalate (DEP) showed strong antiandrogenicity whereas the action of diethylhexyl phthalate (DEHP) dipentyl phthalate (DPP) dimethyl phthalate (DMP) and the DEHP metabolite monoethylhexyl phthalate (MEHP) was lower Our in vitro study demonstrates for the first time a weak antiandrogenic activity of TBBPA and a significant enhancement of the androgenic activity of HBCD BDE-100 and BDE 155 which represents a novel mechanism of hormonal activity of flame retardants (C) 2010 Elsevier Ltd All rights reserved