The toxic effects of three polybrominated diphenyl ether (PBDE) congeners (BDE-47, -99, and -209), tetrabromobisphenol A (TBBPA) and bisphenol A (BPA), were evaluated by determining their 24 hand 96 h median lethal concentrations using a zebrafish liver cell line, ZFL. It was found that BDE-47, BDE-99 and TBBPA showed comparative cytotoxicity within the range of 1.2-4.2 mu M, and were more toxic than BPA (367.1 mu M at 24h and 357.6 mu M at 96 h). However, BDE-209 induced only 15% lethality with exposures up to 25 mu M. The molecular stresses of BDE-47, -99, TBBPA and BPA involved in thyroid hormone (TH) homeostasis and hepatic metabolism were also investigated. Using a reporter gene system to detect zebrafish thyroid hormone receptor beta (zfTR beta) transcriptional activity, the median effective concentration of triiodothyronine (T3) was determined to be 9.2 x 10(-11) M. BDE-47, BDE-99, TBBPA and BPA alone, however, did not exhibit zfTR beta agonistic activity. BPA displayed T3 (0.1 nM) induced zfTR beta antagonistic activity with a median inhibitory concentration of 19.3 mu M. BDE-47, BDE-99 and TBBPA displayed no antagonistic effects of T3-induced zfTR beta activity. Target gene expressions were also examined under acute exposures. The significant inhibition of different types of deiodinases by all of the test chemicals indicated TH circulation disruption. All four chemicals, especially BPA, were able to affect transcripts of phase II hepatic metabolizing enzymes (UGT2A1, SULT1) in vitro. In conclusion, the zfTR beta reporter gene system developed here helps delineate an in vitro model to enable the analysis of the TH disruption effects of environmental pollutants in fish. BPA and the brominated compounds tested were able to disrupt the TH system at the gene expression level, probably through the deiodination pathways. (C) 2014 Elsevier B.V. All rights reserved.
