Biotransformation of Organophosphate Diesters Characterized via In Vitro Metabolism and In Vivo Screening

Organophosphate diesters (di-OPEs), as additives in industrial applications and/or transformation products of emerging environmental pollutants, such as organophosphate triesters (tri-OPEs), have been found in the environment and biological matrices. The metabolic fate of di-OPEs in biological media is of great significance for tracing the inherent and precursor toxicity variations. This is the first study to investigate the metabolism of a suite of di-OPEs by liver microsomes and to identify any metabolite of metabolizable di-OPEs in in vitro and in vivo samples. Of the 14 di-OPEs, 5 are significantly metabolizable, and their abundant metabolites with hydroxyl, carboxyl, dealkylated, carbonyl, and/or epoxide groups are tentatively identified. More than half of the di-OPEs are detectable in human serum and/or wild fish tissues, and dibenzyl phosphate (DBzP), bis(2,3-dibromopropyl) phosphate (BDBPP), and isopropyl diphenyl phosphate (ip-DPHP) are first reported at a detectable level in humans and wildlife. Using an in vitro assay and a known biotransformation rule-based integrated screening strategy, 2 and 10 suspected metabolite peaks of DEHP are found in human serum and wild fish samples, respectively, and are then identified as phase I and phase II metabolites of DEHP. This study provides a novel insight into fate and persistence of diOPE and confirms the presence of di-OPE metabolites in humans and wildlife.