In Vitro metabolism of six representative organic UV stabilizers (OUVs) in marine fish liver microsomes: Kinetics, mechanisms and bioaccumulation evaluation

The ubiquitous occurrence of organic UV stabilizers (OUVs) poses a potential threat to marine fish, but the metabolism of OUVs in the body remains a missing piece of the puzzle in their ecotoxicology. This study investigated the in vitro metabolism of six OUVs in the liver microsomes of an economically valuable marine fish ( Lateolabrax japonicus ). The depletion of the six OUVs follows first-order kinetics in the microsomes, with in vitro depletion rate constants ( k depl ) ranging from 0.23 to 0.40/h. The intrinsic clearance ( CL int ) of 1H-benzotriazole (BT) was estimated to be 0.0026  μ L/(min·mg·protein). The enzyme inhibition experiments and molecular docking results highlight the importance of cytochrome P450 enzyme (CYP) 3A4 in OUVs metabolism. Among the 4 metabolizable compounds, some metabolites from hydroxylation, methylation, acetylation and conjugation were tentatively identified. In addition, the in vitro transformation rates can more accurately predict the whole-body bioconcentration potential via an in vitro to in vivo extrapolation (IVIVE) model.