The enantiomer-selective metabolism of hexabromocyclododecanes (HBCDs) by human HepG2 cells.

Although hepatic metabolism of hexabromocyclododecanes (HBCDs) played critical roles in the selective bioaccumulation of HBCDs in humans, the hepatic metabolism patterns of its enantiomers remained ambiguous. Aiming to elucidate the mechanism on hepatic metabolism of hexabromocyclododecanes (HBCDs) enantiomers, the enantiomers ((+)-α-HBCD, (-)-α-HBCD, (+)-γ-HBCD, and (-)-γ-HBCD), the diastereoisomers (α-, β-, and γ-HBCDs) and the mixed of α- and γ-HBCDs were incubated with human HepG2 cell under different exposure levels in the present study. The clearance percentages ranked as γ-HBCD enantiomers >β-HBCD enantiomers >α-HBCD enantiomers at the same exposure levels. The clearance percentages of (+)- and (-)-α-HBCDs increased when cells were exposed to racemic α-HBCD and the mixture of racemic α- and γ-HBCDs (p < 0.05). (-)-γ-HBCD was more resistant to human hepatic metabolism than (+)-γ-HBCD, leading to the enantiomer fractions (EFs) of γ-HBCD lower than 0.50. (-)-α-HBCD was slightly more metabolized when independently exposed to α-HBCD, while (+)-α-HBCD was more preferentially metabolized after exposure to α- and γ-HBCD mixtures. Hydroxylation and debromination HBCD metabolites were identified. In addition, the different EFs of HBCDs in cells and mediums suggested the selective transfer of chiral HBCDs and HBCD metabolites through the cell membrane. This study provided new insight into the enantiomer-selective metabolism of HBCDs.