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三苯基磷酸酯及其主要代谢物二苯基磷酸酯的生物转化、生物积累和生物消除。

Biotransformation, Bioaccumulation, and Bioelimination of Triphenyl Phosphate and Its Dominant Metabolite Diphenyl Phosphate .

机构信息

State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210023, China.

School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

出版信息

Environ Sci Technol. 2024 Sep 3;58(35):15486-15496. doi: 10.1021/acs.est.4c04782. Epub 2024 Aug 21.

DOI:10.1021/acs.est.4c04782
PMID:39167085
Abstract

Aryl phosphorus flame retardants (aryl-PFRs), such as triphenyl phosphate (TPHP) and diphenyl phosphate (DPHP), are widely used worldwide. Understanding the fates of aryl-PFRs is crucial to assessing their toxicity and the risks they pose. Seven TPHP metabolites, including Phase I hydrolysis and hydroxylation and Phase II glucuronidation products, were identified in C57BL/6J male mice following subacute dietary exposure to aryl-PFRs (70 μg/kg body weight (bw)/day) for 7 days. TPHP was almost completely metabolized by mice (∼97%), with DPHP the major metabolite formed (34%-58%). In addition, mice were exposed to aryl-PFRs (7 μg/kg bw/day) for 12 weeks. Both TPHP and DPHP occurred at higher concentrations in the digestive tract (intestine and stomach), liver and heart. The total concentration of DPHP in all organs was 3.55-fold greater than that of TPHP. Recovery analysis showed that the rate of TPHP elimination from mouse organs reached 38%, while only 3%-5% of DPHP was removed, suggesting that the rates of degradation and elimination of DPHP were slower than TPHP and its bioaccumulation potential was higher. These results highlight the critical role of DPHP in the biotransformation, bioaccumulation, and bioelimination of TPHP, providing valuable insights into the fate of aryl-PFRs .

摘要

芳基磷系阻燃剂(aryl-PFRs),如磷酸三苯酯(TPHP)和磷酸二苯酯(DPHP),在全球范围内被广泛使用。了解芳基-PFRs 的命运对于评估其毒性和所带来的风险至关重要。在亚急性经口暴露于芳基-PFRs(70μg/kg 体重/天)7 天后,在 C57BL/6J 雄性小鼠中鉴定出 7 种 TPHP 代谢物,包括 I 相水解和羟化以及 II 相葡萄糖醛酸化产物。TPHP 几乎被小鼠完全代谢(约 97%),形成的主要代谢物为 DPHP(34%-58%)。此外,小鼠还暴露于芳基-PFRs(7μg/kg bw/day)12 周。TPHP 和 DPHP 在消化道(肠和胃)、肝脏和心脏中的浓度均较高。所有器官中 DPHP 的总浓度是 TPHP 的 3.55 倍。回收分析表明,TPHP 从小鼠器官中的消除率达到 38%,而 DPHP 的消除率仅为 3%-5%,这表明 DPHP 的降解和消除率比 TPHP 慢,其生物累积潜力更高。这些结果突出了 DPHP 在 TPHP 的生物转化、生物累积和生物消除中的关键作用,为芳基-PFRs 的命运提供了有价值的见解。

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