Neonatal triphenyl phosphate and its metabolite diphenyl phosphate exposure induce sex- and dose-dependent metabolic disruptions in adult mice.

The widespread application of organophosphorous flame retardants (OPFRs) has led to considerable human exposure, with major concerns regarding their health risks. Herein, we investigate the effects of triphenyl phosphate (TPP), one of the most widely used OPFRs, and one of its main metabolite diphenyl phosphate (DPP) on the endocrine systems and metabolic profiles after neonatal exposure from postnatal days 1-10 at two dosages (2 and 200 μg per day). Both TPP and DPP had no negative effect on uterine weight, glucose tolerance, and estradiol. 1H-NMR-based metabolomics revealed a sex-specific metabolic disturbance of TPP. Specifically, low dose of TPP altered the metabolic profiles of male mice while exerting no significant effects on female ones. Furthermore, a dose-dependent effect of TPP in male mice was observed, where a low toxicity dose up-regulated lipid-related metabolites, while a high toxicity dose down-regulated the pyruvate metabolism and TCA cycles. These results highlight the importance of carefully assessing the health impact of TPP on infants.