Calafat Antonia M, Brock John W, Silva Manori J, Gray L Earl, Reidy John A, Barr Dana B, Needham Larry L
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Hwy., NE, Mailstop F17, Atlanta, GA 30341, USA.
Toxicology. 2006 Jan 5;217(1):22-30. doi: 10.1016/j.tox.2005.08.013. Epub 2005 Sep 19.
Two studies were designed to examine amniotic fluid and maternal urine concentrations of the di(2-ethylhexyl) phthalate (DEHP) metabolite mono(2-ethylhexyl) phthalate (MEHP) and the di-n-butyl phthalate (DBP) metabolite monobutyl phthalate (MBP) after administration of DEHP and DBP during pregnancy. In the first study, pregnant Sprague-Dawley rats were administered 0, 11, 33, 100, or 300 mg DEHP/kg/day by oral gavage starting on gestational day (GD) 7. In the second study, DBP was administered by oral gavage to pregnant Sprague-Dawley rats at doses of 0, 100, or 250 mg/kg/day starting on GD 13. Maternal urine and amniotic fluid were collected and analyzed to determine the free and glucuronidated levels of MEHP and MBP. In urine, MEHP and MBP were mostly glucuronidated. By contrast, free MEHP and free MBP predominated in amniotic fluid. Statistically significant correlations were found between maternal DEHP dose and total maternal urinary MEHP (p=0.0117), and between maternal DEHP dose and total amniotic fluid MEHP levels (p=0.0021). Total maternal urinary MEHP and total amniotic fluid MEHP levels were correlated (Pearson correlation coefficient=0.968). Statistically significant differences were found in amniotic MBP levels between animals within the same DBP dose treatment group (p<0.0001) and between animals in different dose treatment groups (p<0.0001). Amniotic fluid MBP levels increased with increasing DBP doses, and high variability in maternal urinary levels of MBP between rats was observed. Although no firm conclusions could be drawn from the urinary MBP data, the MEHP results suggest that maternal urinary MEHP levels may be useful surrogate markers for fetal exposure to DEHP.
两项研究旨在检测孕期给予邻苯二甲酸二(2-乙基己基)酯(DEHP)和邻苯二甲酸二正丁酯(DBP)后,羊水和母体尿液中DEHP代谢物单(2-乙基己基)邻苯二甲酸酯(MEHP)以及DBP代谢物单丁基邻苯二甲酸酯(MBP)的浓度。在第一项研究中,从妊娠第7天开始,对妊娠的斯普拉格-道利大鼠经口灌胃给予0、11、33、100或300mg DEHP/kg/天。在第二项研究中,从妊娠第13天开始,对妊娠的斯普拉格-道利大鼠经口灌胃给予DBP,剂量为0、100或250mg/kg/天。收集并分析母体尿液和羊水,以测定MEHP和MBP的游离水平和葡萄糖醛酸化水平。在尿液中,MEHP和MBP大多为葡萄糖醛酸化形式。相比之下,羊水以游离MEHP和游离MBP为主。在母体DEHP剂量与母体尿液总MEHP之间(p = 0.0117)以及母体DEHP剂量与羊水总MEHP水平之间(p = 0.0021)发现有统计学意义的相关性。母体尿液总MEHP和羊水总MEHP水平具有相关性(皮尔逊相关系数 = 0.968)。在同一DBP剂量治疗组内的动物之间(p < 0.0001)以及不同剂量治疗组的动物之间(p < 0.0001),羊水MBP水平存在统计学意义的差异。羊水MBP水平随DBP剂量增加而升高,并且观察到大鼠母体尿液MBP水平存在高度变异性。虽然从尿液MBP数据无法得出确切结论,但MEHP的结果表明,母体尿液MEHP水平可能是胎儿暴露于DEHP的有用替代标志物。