Plasma protein binding, metabolic stability, oral bioavailability and disposition kinetics of bisphenol AP in rats

Bisphenol A (BPA) is a recognised endocrine disruptor resulting in regulatory restrictions and a search for safer alternatives. Bisphenol AP (BPAP), introduced as a BPA substitute, has shown endocrine-disrupting potential and is linked to genotoxicity and recurrent miscarriages. Toxicokinetic evaluation is essential for health risk assessment, yet data on BPAP are lacking. This study characterizes the in vitro and in vivo TK profile of BPAP to facilitate its comparative risk assessment with BPA. A sensitive LC-MS/MS method was developed and validated for quantifying BPAP in rat plasma. In vitro assessments revealed high plasma protein binding in rat and human plasma and indicated metabolism through glucuronidation. Predicted hepatic clearance using the well-stirred model suggested BPAP as a high and intermediate extraction chemical in rats and humans, respectively. In vivo studies showed rapid oral absorption and high clearance (4.24 L/h/kg) after intravenous dosing. BPAP exhibited 18% oral bioavailability. BPAP excretion studies showed feces as major elimination route, with negligible urinary excretion. These findings provide insights into BPAP's disposition profile and highlight that BPAP may not be a safer replacement analogue. This study emphasize the need for further toxicity studies and risk evaluation before considering BPAP a safer BPA alternative.