Investigation on Sex Hormone-Disruption Effects of Two Novel Brominated Flame Retardants (DBDPE and BTBPE) in Male Zebrafish (_Danio rerio_) and Two Human Cell Lines (H295R and MVLN)  
[PERSON]  
1 School of Public Health, Seoul National University, Seoul 08826, Korea; [EMAIL_ADDRESS] (J.C.); [EMAIL_ADDRESS] (G.L.); [EMAIL_ADDRESS] (S.K.)  
[PERSON]  
1 School of Public Health, Seoul National University, Seoul 08826, Korea; [EMAIL_ADDRESS] (J.C.); [EMAIL_ADDRESS] (G.L.); [EMAIL_ADDRESS] (S.K.)  
[PERSON]  
1 School of Public Health, Seoul National University, Seoul 08826, Korea; [EMAIL_ADDRESS] (J.C.); [EMAIL_ADDRESS] (G.L.); [EMAIL_ADDRESS] (S.K.)  
[PERSON]  
1 School of Public Health, Seoul National University, Seoul 08826, Korea; [EMAIL_ADDRESS] (J.C.); [EMAIL_ADDRESS] (G.L.); [EMAIL_ADDRESS] (S.K.)  
Footnote 1: email: {choi,j,lee,g;kim,s  
in production and usage in 2001, while more recent information is not readily available [15]. Increasing use of DBDPE and BTBPE as flame retardants has resulted in their frequent and widespread occurrences in various environments [16]. DBDPE and BTBPE have been detected in Chinese wastewater at levels up to 22.3 ng/L and 2.2 ng/L, respectively [17]. The concentrations of DBDPE and BTBPE in surface sediments in China have been observed at up to 20.6 ng/g dw and 0.32 ng/g dw, respectively [18]. Furthermore, studies reported that DBDPE and BTBPE had degradation and bioaccumulation characteristics similar to those of PBDEs [19; 20; 21; 22; 23]. DBDPE has been suggested as persistent in the environment, e.g., no degradation for 112 days in a sunlit condition [24]. BTBPE was reported for its depration half-life of 54.1 days in juvenile rainbow trout [25]. Considering their increasing use, widespread environmental occurrences, and potential bioaccumulation potentials, studies that look at toxicological consequences of these chemicals are necessary [3].  
Considering the physicochemical similarities between PBDEs and these NBFRs, sex hormone-disruption potentials could be suspected for these two NBFRs. Most of the toxicological studies that have been conducted for DBDPE and BTBPE have been focused on the neurotoxic or thyroid hormone disrupting potential, but information on the sex hormone disrupting effects of these two NBFRs is very restricted [26; 27]. In previous studies, DBDPE and BTBPE exposure in fish led to observations that were suggestive of their sex hormones-disruption potentials, e.g., up-regulation of \(vtg\) gene or increased vitellogenin (\(vtg\)), which were similar to the observations on PBDEs [28; 29; 30]. Since sex hormones play crucial roles in gonad gametogenesis and the reproductive function of animals [4; 31], understanding the sex hormone-disruption potentials of emerging chemicals is warranted.  
The objective of this study is to enhance understanding of the sex hormone-disruption effects and the related mechanism of two NBFRs, DBDPE and BTBPE. For this purpose, zebrafish (_Danio rerio_) was used. Zebrafish have been frequently used as one of the experimental models for screening endocrine disrupting chemicals because of cost-effectiveness, rapid life stage, and similarity in endocrine system with other vertebrates [32]. In addition, two human tissue cell lines, i.e., H295R (human adrenocortical carcinoma) and MVLN (human breast carcinoma) cells, were chosen to evaluate the effects on sex hormones synthesis and the related mechanisms. H295R cell line and MVLN cell line have been used to observe a potential alteration in the steroidogenesis pathway [33] and binding affinity to estrogen receptor (ER) [34; 35; 36; 37], respectively.