Hydrolysis of di(2-ethylhexyl) phthalate in humans, monkeys, dogs, rats, and mice: An in vitro analysis using liver and intestinal microsomes
Hydrolysis of di(2-ethylhexyl) phthalate in humans, monkeys, dogs, rats, and mice: An in vitro analysis using liver and intestinal microsomes
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人、猴、狗、大鼠和小鼠体内邻苯二甲酸二（2-乙基己基）酯的水解：使用肝脏和肠道微粒体的体外分析
DOI：
10.1016/j.tiv.2018.10.006
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
and Hideto Jinno
中科院分区：
文献类型：
--
作者：
Nobumitsu Hanioka;Takashi Isobe;Susumu Ohkawara;Sadayuki Ochi;Toshiko Tanaka-Kagawa;and Hideto Jinno
邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种广泛使用的增塑剂，在哺乳动物体内能迅速代谢成活性代谢物邻苯二甲酸单酯(MEHP)。在本研究中，研究了人、猴、狗、大鼠和小鼠的肝脏和肠道微粒体对DEHP的水解性。人、猴、大鼠肝微粒体动力学符合Michaelis-Menten模型，狗和小鼠符合Hill模型。KmorS50值在物种间相似，而Vmax显示物种差异约9倍。CLintorCLmax的大小顺序为mice >； dogs >； monkeys ≥ rats >； humans.在人和狗的肠道微粒体中未检测到对DEHP的水解性。猴子、大鼠和小鼠的动力学符合Hill模型。在比较每个物种的肝微粒体时，S50值相似，而Vmax和CLmax(小鼠 >； 大鼠 >； 猴)要低得多(约5-25%)。这些结果表明，人与非啮齿动物和啮齿动物的肝脏和肠道对DEHP的水解性明显不同，表明物种差异与DEHP的毒性密切相关。
Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that is rapidly metabolized to mono(2-ethylhexyl) phthalate (MEHP), an active metabolite, in mammals. In the present study, the hydrolysis of DEHP by the liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice was examined. The kinetics of liver microsomes fit the Michaelis-Menten model for humans, monkeys, and rats, and the Hill model for dogs and mice.KmorS50values were similar among species, whereasVmaxexhibited species differences of approximately 9-fold.CLintorCLmaxvalues were in the order of mice > dogs > monkeys ≥ rats > humans. Hydrolytic activity towards DEHP was not detected in the intestinal microsomes of humans or dogs. The kinetics of monkeys, rats, and mice followed the Hill model. In comparisons of the liver microsomes of each species,S50values were similar, whileVmaxandCLmaxvalues (mice > rats > monkeys) were considerably lower (approximately 5–25%). These results suggest that hydrolytic activity towards DEHP in the liver and intestines markedly differ among humans and non-rodent and rodent experimental animals, and imply that species differences are closely associated with the toxicity of DEHP.