Investigating the glucuronidation and sulfation pathways contribution and disposition kinetics of Bisphenol S and its metabolites using LC-MS/MS-based nonenzymatic hydrolysis method

Abstract

Despite showing serious health consequences and widespread exposure, the toxicokinetic information required to evaluate the health risks of BPS is insufficient. Thus, we aim to describe the comprehensive toxicokinetics of BPS and its glucuronide (BPS-G) and sulfate (BPS–S) metabolites in rats. Simultaneous quantification of BPS and its metabolites (authentic standards) was accomplished using UPLC-MS/MS method. BPS displayed rapid absorption, extensive metabolism and fast elimination after oral administration. Following intravenous administration, BPS exhibited CL (8.8 L/h/kg) higher than the rat hepatic blood flow rate suggesting the likelihood of extrahepatic clearance. The CL value differed from those reported previously (sheep and piglets) and the probable reason could be attributed to dose- and/or interspecies differences. BPS was extensively metabolized and excreted primarily through urine as BPS-G (∼56%). BPS and BPS-S exhibited a high protein binding capacity in comparison to BPS-G. In in vitro metabolic stability study, BPS was predominantly metabolized through glucuronidation. The predicted in vivo hepatic clearance of BPS suggested it to be a high and intermediate clearance chemical in rats and humans, respectively. The significant interspecies difference observed in the clearance of BPS between rats and humans indicated that toxicokinetics of BPS should be considered for health risk assessment in humans.