磷酸三(2-丁氧基乙基)酯及其代谢产物在大鼠体内的排泄动力学研究
Excretion Kinetics of Tris(2-butoxyethyl) Phosphate and Its Metabolites in Rats
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摘要: 磷酸三(2-丁氧基乙基)酯(tris (2-butoxyethyl) phosphate,TBOEP)作为一种新污染物在环境中已广泛被检出,但当前关于TBOEP的毒代动力学研究仍较为缺乏。为此,本研究旨在探索TBOEP及其代谢物在雄性SD大鼠体内的代谢及排泄规律。本研究将健康成年雄性SD大鼠经口单剂量给予750 mg·kg-1 TBOEP后,收集0~24 h、24~48 h、48~72 h、72~96 h、96~120 h、120~144 h和144~168 h不同时间段尿液和粪便样本,采用液相色谱-质谱联用仪测定TBOEP及其代谢物的含量。结果表明,染毒后,TBOEP及其代谢物双(丁氧基乙基)磷酸酯(bis (2-butoxyethyl) phosphate,BBOEP)、双(2-丁氧基乙基)-2-羟基乙基磷酸三酯(bis (2-butoxyethyl)-(2-hydroxyethyl) phosphate,BBOEHEP)在所有尿液和粪便样品中检出,双(2-丁氧基乙基)-2-(3-羟丁氧基)乙基磷酸三酯(tris (2-(3-hydroxy) butoxyethyl) phosphate,3-OH-TBOEP)仅在0~24 h粪便样品中检出。染毒后168 h内,TBOEP尿液和粪便累积排泄率为0.004%、0.422%,BBOEP尿液和粪便累积排泄率为0.007%、0.3931%,BBOEHEP尿液和粪便累积排泄率为0.011%、0.0434%,提示TBOEP及其代谢物BBOEP主要通过粪便排泄,而代谢物BBOEHEP通过尿液和粪便排泄。结果表明,BBOEP和BBOEHEP可能是TBOEP在大鼠体内主要的代谢产物。仅有极少部分的TBOEP代谢为3-HO-TBOEP,提示可能存在其他的生物转化过程。研究结果将为阐明TBOEP的毒代动力学规律提供科学依据。
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关键词:
- 磷酸三(2-丁氧基乙基)酯(TBOEP) /
- 大鼠 /
- 排泄动力学 /
- 代谢产物
Abstract: Ris(2-butoxyethyl) phosphate (TBOEP) is an emerging pollutant widely detected in the environment, whereas the current understanding on its toxicokinetics is still limited. In this study, we investigated the excretion of TBOEP and its metabolites in the urine and feces of healthy adult male SD rats. A single dose of 750 mg·kg-1 TBOEP were administered to male SD rats orally, and their urine and feces samples were collected at different time periods of 0~24, 24~48, 48~72, 72~96, 96~120, 120~144 and 144~168 h after administration. TBOEP and its metabolites were determined via a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The results showed that TBOEP and its metabolite bis(2-butoxyethyl) phosphate (BBOEP) and bis(2-butoxyethyl)-(2-hydroxyethyl) phosphate (BBOEHEP) were detected in all the urine and feces samples, whereas tris(2-(3-hydroxy)butoxyethyl) phosphate (3-OH-TBOEP) was only detected in feces samples collected at 0~24 h. The cumulative excretion rates in urine and feces were calculated a week after administration, with 0.004% and 0.422% for TBOEP, 0.007% and 0.3931% for BBOEP, and 0.011% and 0.0434% for BBOEHP, respectively. These results indicated that BBOEP and BBOEHEP may be the main metabolites of TBOEP in rats. However, only a small amount of TBOEP was converted into 3-HO-TBOEP, suggesting there might be other biotransformation processes. This study provided scientific evidence to elucidate the toxicokinetic mechanisms of TBOEP.-
Key words:
- tris(2-butoxyethyl) phosphate (TBOEP) /
- rats /
- excretion kinetics /
- metabolites
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