Biotransformation, Physico-Chemical Properties and Environmental Fate of Bisphenol A Bis(Diphenyl Phosphate): In Slico, In Vitro and Non-Target Metabolites using a Wister-Han Rat Liver Microsomal Model

Abstract

Organophosphate ester (OPE) flame retardants and plasticizers have replaced several legacy, banned brominated flame retardants. Bisphenol A bis(diphenyl phosphate) (BPADP) exemplifies a growing industry trend towards production of complex, high molecular weight, 'novel' OPEs. An assay method was optimized for quantification of BPADP biotransformation to target metabolites bisphenol-A (BPA) and diphenyl phosphate (DPHP) in an in vitro Wistar-Han rat liver microsomal assay. In silico modelling via OECD Toolbox v4.4.1 and Non-Target Analysis (NTA) via Q-E-Orbitrap HRMS/MS were applied to predict physico-chemical properties and identify additional non-targeted metabolites of BPADP. DPHP and BPA were predicted in silico and confirmed in vitro, with BPADP demonstrating slow in vitro microsomal metabolism.