代谢
乙基 2,3-(14)C-丙烯酸通过口服灌胃给予大鼠,剂量为 2、20 和 200 mg/kg 体重...主要代谢物是 (14)CO2,24 小时内呼出的比例为 52-61%...确定了三种代谢物:3-羟基丙酸和两种巯基尿酸。N-乙酰-S-(2-羧基乙基)半胱氨酸是通过丙烯酸的谷胱甘肽结合产生的,而 N-乙酰-S-(2-羧基乙基)半胱氨酸乙酯则来源于完整乙基丙烯酸的共轭反应。随着剂量的增加,以这些巯基尿酸形式排泄的剂量百分比下降,与谷胱甘肽的消耗一致。尽管乙基丙烯酸不会减少肝脏中的非蛋白质硫醇,但在前胃和腺胃中出现了明显的剂量依赖性减少,这种减少可以通过用酯酶抑制剂三(邻-甲苯基)磷酸预处理大鼠来增强。这些数据与乙基丙烯酸的水解是一种全身解毒反应相一致,因为丙烯酸对非蛋白质硫醇水平没有影响。
Ethyl 2,3-(14)C-acrylate to rats orally by gavage at doses of 2, 20 and 200 mg/kg bw ...The major metabolite was (14)CO2, with 52-61% exhaled within 24 hr ... Three metabolites were identified: 3-hydroxypropionic acid and two mercapturic acids. N-Acetyl-S-(2-carboxyethyl)cysteine arises by glutathione conjugation of acrylic acid, while N-acetyl-S-(2-carboxyethyl)cysteine ethyl ester derives from the conjugation of intact ethyl acrylate. The percentage of the dose excreted as these mercapturic acids falls with increasing dose, consistent with depletion of glutathione. Although ethyl acrylate does not reduce non-protein sulfhydryls in the liver, marked and dose-dependent depletion occurs in the forestomach and glandular stomach, which is enhanced by pretreatment of rats with the esterase inhibitor tri(ortho-cresyl)phosphate. These data are consistent with the hydrolysis of ethyl acrylate being a systemic detoxication reaction, since acrylic acid has no effect on non-protein sulfhydryl levels.
来源:Hazardous Substances Data Bank (HSDB)