Quantitative Toxicokinetic Investigation of Emerging Aryl Organophosphate Esters in Rats

As substitutes for traditional organophosphate esters (tOPEs), the safety of emerging aryl-OPEs (aryl-eOPEs) requires further evaluation. Understanding their fates in organisms is crucial for assessing potential toxicity and health risks. This study quantitatively investigated the toxicokinetics of four aryl-eOPEs and compared them with tOPEs in Sprague-Dawley rats (n = 72) over a 20-day gavage exposure followed by a 9-day elimination period. The absorption rates of aryl-eOPEs (8.95-28.0%) were approximately 1/2 to 1/10 those of tOPEs (61.9-96.8%), with hydrophobicity and molecular weight being key impact factors. The total concentration of aryl-eOPEs in feces was nearly double that of tOPEs, yet only 6.86-23.6% resulted from metabolic clearance in rats. Most administered aryl-eOPEs were not absorbed by the body and were directly excreted via feces. However, the half-lives of aryl-eOPEs in rats were generally longer than those of tOPEs, with bisphenol A bis(diphenyl phosphate) exhibiting the longest half-life (2.68-6.59 days), highlighting their potential health risks. Additionally, significant pulmonary accumulation of aryl-eOPEs was observed, with the liver, kidneys, and small intestines playing key roles in metabolism and clearance. This study elucidates the toxicokinetic behavior of aryl-eOPEs in mammals and highlights the influence of their physicochemical properties. These findings provide a scientific foundation for assessing their potential health effects.