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N-甲基吡咯烷酮经皮给药于斯普拉格-道利大鼠后的致畸性研究。

Teratogenicity study of N-methylpyrrolidone after dermal application to Sprague-Dawley rats.

作者信息

Becci P J, Knickerbocker M J, Reagan E L, Parent R A, Burnette L W

出版信息

Fundam Appl Toxicol. 1982 Mar-Apr;2(2):73-6. doi: 10.1016/s0272-0590(82)80117-6.

DOI:10.1016/s0272-0590(82)80117-6
PMID:7185604
Abstract

Teratogenicity studies were performed in rats given N-methylpyrrolidone, a solvent used in chemical processing. Dosages of 75,237 and 750 mg of N-methylpyrrolidone/kg body weight/day were administered dermally to groups of 25 pregnant Sprague-Dawley rats on days 6 through 15 of gestation. Additionally, the study used a positive dermal control. Hexafluoroacetone, was chosen based on its dermal teratogenic activity. An oral positive control, aspirin, was included in order to add significance to the data generated in the experimental positive dermal control group. All animals were killed and subjected to uterine examination on day 20 of gestation. Maternal toxicity was indicated at 750 mg of N-methylpyrrolidone/kg by reduced body weight gain during gestation. Treatment with N-methylpyrrolidone resulted in dose-dependent brightly colored yellow urine and dry skin. Treatment at the high dosage level resulted in fewer live fetuses per dam, an increase in the percentage of resorption sites and skeletal abnormalities. These effects could be the result of maternal toxicity. There was no evidence of teratogenic effects nor effects on the dams at 75 and 237 mg/kg of body weight.

摘要

在给予化学加工中使用的溶剂N-甲基吡咯烷酮的大鼠中进行了致畸性研究。在妊娠第6至15天,将剂量为75、237和750毫克N-甲基吡咯烷酮/千克体重/天经皮给予25只怀孕的斯普拉格-道利大鼠组。此外,该研究使用了阳性皮肤对照。基于其皮肤致畸活性选择了六氟丙酮。为了使实验性阳性皮肤对照组产生的数据更具意义,纳入了口服阳性对照阿司匹林。所有动物在妊娠第20天处死并进行子宫检查。在剂量为750毫克N-甲基吡咯烷酮/千克时,显示出母体毒性,表现为妊娠期间体重增加减少。用N-甲基吡咯烷酮治疗导致尿液呈剂量依赖性亮黄色和皮肤干燥。高剂量水平治疗导致每只母鼠的活胎数量减少、吸收部位百分比增加和骨骼异常。这些影响可能是母体毒性的结果。在体重为75和237毫克/千克时,没有致畸作用或对母鼠有影响的证据。

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