Biotransformation,\nBioaccumulation, and Bioelimination\nof Triphenyl Phosphate and Its Dominant Metabolite Diphenyl Phosphate <i>In Vivo</i>

Aryl phosphorus flame retardants (aryl-PFRs), such as\ntriphenyl\nphosphate (TPHP) and diphenyl phosphate (DPHP), are widely used worldwide.\nUnderstanding the fates of aryl-PFRs <i>in vivo</i> is crucial\nto assessing their toxicity and the risks they pose. Seven TPHP metabolites,\nincluding Phase I hydrolysis and hydroxylation and Phase II glucuronidation\nproducts, were identified in C57BL/6J male mice following subacute\ndietary exposure to aryl-PFRs (70 μg/kg body weight (bw)/day)\nfor 7 days. TPHP was almost completely metabolized by mice (∼97%),\nwith DPHP the major metabolite formed (34%–58%). In addition,\nmice were exposed to aryl-PFRs (7 μg/kg bw/day) for 12 weeks.\nBoth TPHP and DPHP occurred at higher concentrations in the digestive\ntract (intestine and stomach), liver and heart. The total concentration\nof DPHP in all organs was 3.55-fold greater than that of TPHP. Recovery\nanalysis showed that the rate of TPHP elimination from mouse organs\nreached 38%, while only 3%–5% of DPHP was removed, suggesting\nthat the rates of degradation and elimination of DPHP were slower\nthan TPHP and its bioaccumulation potential was higher. These results\nhighlight the critical role of DPHP in the biotransformation, bioaccumulation,\nand bioelimination of TPHP, providing valuable insights into the fate\nof aryl-PFRs <i>in vivo</i>.