Biotransformation of OH-PBDEs by pig liver microsomes: Investigating kinetics, identifying metabolites, and examining the role of different CYP isoforms

• OH-PBDEs were more readily metabolized by pig liver microsomes than PBDEs.
• Biotransformation rates of OH-PBDEs decreased with increasing bromine substitution.
• CYP3A4 was suggested to be the primary isoform responsible for OH-PBDEs metabolism.
• Metabolism pathways included ether cleavage, hydroxylation, and debromination.
• Yield of 2,4-DBP was higher than those of 4-BP and 2-BP.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are of great concern due to their potential risk to animal and human health. The biotransformation potential of OH-PBDEs in organisms is important for the understanding of their health risk. In the present study, the biotransformation of 3′-OH-2,4-di-BDE (3′-OH-BDE-7), 4′-OH-2,2′,4-tri-BDE (4′-OH-BDE-17) and 3-OH-2,2′,4,4′-tetra-BDE (3-OH-BDE-47) by pig liver microsomes was studied. Compared with their precursor PBDEs, the three OH-PBDEs were more readily biotransformed by pig liver microsomes, and the biotransformation rate followed the order: 3′-OH-BDE-7 > 4′-OH-BDE-17 > 3-OH-BDE-47. These results revealed that the biotransformation rate of OH-PBDEs was decreased with an increase in the number of bromine substituents. Cleavage of the diphenyl ether bond was the dominant pathway for biotransformation of the three OH-PBDEs by pig liver microsomes, while debromination and hydroxylation were found to be of less importance. CYP3A4 was suggested to be the specific enzyme responsible for the biotransformation of OH-PBDEs via associated inhibition assay. These findings may enrich our understanding of health risk associated with OH-PBDEs in mammals and human beings.