A comparative study for organophosphate triesters and diesters in mice via oral gavage exposure: Tissue distribution, excreta elimination, metabolites and toxicity

Abstract

Organophosphate triesters (tri-OPEs) and diesters (di-OPEs) may threaten human health through dietary intake, whereas little information is available about their fate in mammals. Herein, mice exposure experiments were carried out through gavage with six tri-OPEs and six di-OPEs, respectively. The residual levels of di-OPEs in mice were generally higher than those of tri-OPEs. The residual di-OPEs mainly distributed in the liver and blood while the most tri-OPEs remained in stomach, indicating easier transfer and lower metabolism levels of di-OPEs. The accumulation of tri- and di-OPEs with large octanol–water partition coefficients and long carbon chain were observed in tissues and feces, implying that the elimination of these OPEs through fecal excretion is an important elimination pathway. A total of 86 OPE metabolites were found in murine urine and feces, 57 of which were identified for the first time. For tri-OPEs, carboxylated OPEs had higher peak intensities and fewer interference factors among the metabolites, which could serve as ideal biomarkers. The predicted oral median lethal doses of OPEs and corresponding metabolites showed an increased toxicity of some hydroxylated OPEs and di-OPEs, needing further attention. These results provided new insights and evidence on the fates and biomarkers of OPEs exposure for mammals.