代谢
在大鼠体内和体外对增塑剂DEHA的代谢进行了研究,以确定肝脏过氧化物酶体增殖剂浓度变化所涉及的不同步骤。在体内研究中,通过灌胃给Wistar大鼠不同剂量的DEHA和单-(2-乙基己基)-己二酸酯,持续5天。在体外研究中,通过原位灌注分离出肝细胞。在大鼠给药后24小时内,尿液中没有检测到DEHA;己二酸是主要的代谢物。只有2-乙基己醇途径显示出进一步的代谢物,主要是2-乙基己酸,它要么被结合,要么进入其他途径。虽然2-乙基己酸葡萄糖醛酸化似乎与剂量和时间有关,但2-乙基己醇葡萄糖醛酸化更为稳定。在体外,DEHA的首次水解似乎是一个速率限制步骤。当单-(2-乙基己基)己二酸酯直接添加到培养基中时,发现了体内研究中识别的所有代谢物。2-乙基己醇和2-乙基己酸的葡萄糖醛酸化与剂量和时间有关。
In vivo and in vitro metabolism of the plasticizer DEHA was examined in the rat to determine the different steps involved in the hepatic concn of peroxisomal proliferators. In the in vivo studies, different doses of DEHA and mono-(2-ethylhexyl)-adipate were administered by gavage to Wistar rats for 5 days. In the in vitro studies, hepatocytes were isolated by in situ perfusion. No DEHA was recovered in rat urine 24 hr after administration; adipic acid was the main metabolite. Only the 2-ethylhexanol pathway showed further metabolites, mainly 2-ethylhexanoic acid which was either conjugated or submitted to other pathways. While 2-ethylhexanoic acid glucuronidation appeared to be dose and time dependent, 2-ethylhexanol glucuronidation was more stable. In vitro, the first hydrolysis of DEHA appeared to be a rate limiting step. When mono-(2-ethylhexyl) adipate was added directly to the culture medium, all the metabolites identified in the in vivo study were found. Glucuronidation of both 2-ethylhexanol and 2-ethylhexanoic acid was dose and time dependent.
来源:Hazardous Substances Data Bank (HSDB)