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己二酸二(2-乙基己基)酯:在小鼠和大鼠体内的吸收、放射自显影分布及消除

Di-(2-ethylhexyl)adipate: absorption, autoradiographic distribution and elimination in mice and rats.

作者信息

Bergman K, Albanus L

出版信息

Food Chem Toxicol. 1987 Apr;25(4):309-16. doi: 10.1016/0278-6915(87)90128-1.

DOI:10.1016/0278-6915(87)90128-1
PMID:3583157
Abstract

Whole-body autoradiography was used to study the tissue distribution of the plasticizer di-(2-ethylhexyl) adipate (DEHA), labelled in the acid [carbonyl-14C] or alcohol [2-ethylhexyl-1-14C]moiety, after iv or ig administration to male mice and rats and pregnant mice. With both DEHA preparations, during the first 24 hr after administration high levels of radioactivity were observed particularly in the body fat, liver and kidneys (after iv and ig administration) and in the intestinal contents (after ig administration) of both species. After administration of [carbonyl-14C]DEHA, radioactivity was also registered in the adrenal cortex, corpora lutea of the ovary, bone marrow, forestomach mucosa, salivary glands and Harder's gland in both species. [2-ethylhexyl-1-14C]DEHA derived radioactivity was found in the bronchi in male mice. Radioactivity was observed in the foetal liver, intestine and bone marrow during the first 24 hr after iv or ig administration of [carbonyl-14C]DEHA to pregnant mice. There was very little accumulation of [2-ethylhexyl-1-14C]DEHA in the mouse foetus but some was found in the urinary bladder, liver and intestinal contents as well as in the amniotic fluid. In an absorption/elimination study in rats of doses of 25 microCi/kg body weight of [14C]DEHA administered ig, dissolved in corn oil or dimethylsulphoxide, blood levels of radioactivity increased somewhat faster and were two or three times higher when DMSO was the vehicle indicating poor absorption of DEHA from the corn oil solution which more accurately reflects human contact with DEHA. Little radioactivity from [carbonyl-14C]DEHA was recovered in the bile, whereas [2-ethylhexyl-1-14C]DEHA was excreted in the bile in significant amounts particularly when DMSO was the vehicle. There was evidence of enterohepatic circulation of DEHA. Radioactivity was also excreted in the urine. As shown by autoradiograms obtained 4 days after the administration of [14C]DEHA there was no retention of DEHA and/or its metabolites in the tissues of mice.

摘要

采用全身放射自显影技术,研究了己二酸二(2-乙基己基)酯(DEHA)在酸[羰基-14C]或醇[2-乙基己基-1-14C]部分标记后,经静脉注射或灌胃给予雄性小鼠、大鼠及妊娠小鼠后的组织分布情况。对于两种DEHA制剂,给药后的最初24小时内,在两种动物的体脂、肝脏和肾脏(静脉注射和灌胃后)以及肠道内容物(灌胃后)中均观察到高水平的放射性。给予[羰基-14C]DEHA后,在两种动物的肾上腺皮质、卵巢黄体、骨髓、前胃黏膜、唾液腺和哈德氏腺中也检测到放射性。在雄性小鼠的支气管中发现了源自[2-乙基己基-1-14C]DEHA的放射性。给妊娠小鼠静脉注射或灌胃[羰基-14C]DEHA后的最初24小时内,在胎儿肝脏、肠道和骨髓中观察到放射性。[2-乙基己基-1-14C]DEHA在小鼠胎儿中的蓄积很少,但在膀胱、肝脏、肠道内容物以及羊水中发现了一些。在一项大鼠吸收/消除研究中,以25微居里/千克体重的[14C]DEHA溶解于玉米油或二甲基亚砜中进行灌胃给药,当以二甲基亚砜为溶剂时,血液中的放射性水平升高得稍快一些,且高出两到三倍,这表明DEHA从玉米油溶液中的吸收较差,而玉米油溶液更准确地反映了人类与DEHA的接触情况。[羰基-14C]DEHA在胆汁中的放射性回收很少,而[2-乙基己基-1-14C]DEHA大量经胆汁排泄,尤其是当以二甲基亚砜为溶剂时。有证据表明DEHA存在肠肝循环。放射性也经尿液排泄。如给予[14C]DEHA 4天后获得的放射自显影片所示,在小鼠组织中未发现DEHA及其代谢产物的潴留。

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