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家兔吸入2-甲氧基丙醇-1的产前毒性

Prenatal toxicity of inhalation exposure to 2-methoxypropanol-1 in rabbits.

作者信息

Hellwig J, Klimisch H J, Jäckh R

机构信息

Department of Toxicology, BASF Aktiengesellschaft, Federal Republic of Germany.

出版信息

Fundam Appl Toxicol. 1994 Nov;23(4):608-13. doi: 10.1006/faat.1994.1147.

Abstract

2-Methoxypropanol-1 was investigated for prenatal toxicity in Himalayan rabbits after inhalation exposure to 0, 145, 225, 350, and 545 ppm for 6 hr per day from Gestation Day 6 through 18. Maternally toxic effects were found with decreased body weights from Day 12 of gestation through the end of the study at 545 ppm. A dose-dependent increase of resorptions, fetal malformations, and variations was observed at 225, 350, and 545 ppm, whereas 145 ppm was devoid of exposure-related effects. The malformation rate at 545 ppm was 100%. The types of malformations mainly consisted of absent phalanges and absent or rudimentary metatarsal bones, malformed ribs, and a unique enlargement of sternebrae. The effects are very similar to those previously found with 2-methoxypropyl-acetate-1. The results of this study may have implications for the quantitative estimation of risks associated with 2-methoxy-propanol-1 impurities in the widely used isomer 1-methoxypropanol-2 which itself does not show developmental toxicity.

摘要

对喜马拉雅兔进行了2-甲氧基丙醇-1的产前毒性研究,在妊娠第6天至18天期间,每天吸入0、145、225、350和545 ppm的该物质6小时。在545 ppm剂量下,从妊娠第12天到研究结束,母体出现体重下降的毒性效应。在225、350和545 ppm剂量下,观察到吸收、胎儿畸形和变异呈剂量依赖性增加,而145 ppm未出现与暴露相关的效应。545 ppm剂量下的畸形率为100%。畸形类型主要包括指骨缺失、跖骨缺失或发育不全、肋骨畸形以及胸骨节独特增大。这些效应与先前使用2-甲氧基丙酯-1时发现的效应非常相似。本研究结果可能对定量评估与广泛使用的异构体2-甲氧基-1-丙醇中2-甲氧基丙醇-1杂质相关的风险具有启示意义,而2-甲氧基-1-丙醇本身不显示发育毒性。

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