Toxic effects of bisphenol A diglycidyl ether and derivatives in human placental cells

BADGE (bisphenol A diglycidyl ether) is a synthesis product of bisphenol A (BPA), which, like other plasticizers, can cross the human placenta and reach the foetus. However, compared to BPA, there is almost no toxicological information. This work investigates the toxicity, endocrine and lipid disruption potential of BADGE and its hydrolysed and chlorinated derivatives (BADGE center dot H2O and BADGE center dot 2HCl) in human placental JEG-3 cells. The analysis of culture medium by HPLC-ESI(+)-QqQ evidenced a good bioavailability of BADGE center dot 2HCl and BADGE center dot H2O, but low stability of BADGE. Regardless, BADGE center dot 2HCl and BADGE showed higher cytotoxicity than BADGE center dot H2O, which was the only compound that significantly inhibited CYP19 activity (IC50 49 +/- 5 mu M). JEG-3 cells lipidome analyzed by FIA-ESI(+/-)-Orbitrap was significantly altered by exposure to BADGE center dot 2HCl and BADGE at concentrations at the low mu M range. BADGE center dot 2HCl lead to a strong decrease of diacyl- and triacyl-glycerides (DGs,TGs) together with some membrane lipids, while BADGE lead to an accumulation of TGs. The results evidence the ability of BADGE and derivatives to affect placental lipid handling and to modulate placental CYP19 activity (BADGE center dot H2O) and highlights the need to monitor human exposure to these compounds, at least as intensely as BPA is monitored. (C) 2018 Elsevier Ltd. All rights reserved.