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2-溴丙烷对 ICR 小鼠孕鼠及其胚胎-胎儿发育的影响。

Effects of 2-bromopropane on pregnant dams and embryo-fetal development in the ICR mouse.

机构信息

Department of Toxicology, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.

出版信息

Environ Toxicol Pharmacol. 2004 Jan;15(2-3):103-10. doi: 10.1016/j.etap.2003.11.003.

Abstract

2-Bromopropane (2-BP), a halogenated propane analogue, is a substitute for chlorofluorocarbones (CFCs) which have a great potential to destroy the ozone layer and to warm the earth's environment. The present study was carried out to investigate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GD) 6-17 in ICR mice. The test chemical was administered subcutaneously to pregnant mice at dose levels of 0, 500, 1000, and 1500mg/kg per day. All dams were subjected to caesarean section on GD 18 and their fetuses were examined for external, visceral and skeletal abnormalities. Throughout the study period, no treatment-related deaths were found in the groups treated with 2-BP. Pregnant mice of the 1000 and 1500mg/kg groups showed treatment-related clinical signs such as rough fur and swelling, induration, crust formation, and ulceration in the injection sites which were dose dependent in incidence and severity. A decrease in fetal weight, an increase in fetal malformation, and an increase in fetal ossification delay were found at a dose level of 1500mg/kg per day in a dose-dependent manner. On the contrary, there were no adverse effects on body weight, body weight gain, gravid uterine weight, food consumption, gross finding at any dose tested. In addition, no treatment-related effects on the number of corpora lutea, implantations, resorptions, dead fetuses, live fetuses, and sex ratio of live fetuses were observed. These findings suggest that 2-BP was embryotoxic and teratogenic at a minimally maternally toxic dose (i.e., 1500mg/kg per day) in ICR mice. In the present experimental conditions, the no-observed-adverse-effect level of 2-BP is considered to be 500mg/kg per day for dams and 1000mg/kg per day for fetuses, respectively.

摘要

2-溴丙烷(2-BP)是一种卤代丙烷类似物,是氯氟碳化合物(CFCs)的替代品,CFCs 具有破坏臭氧层和使地球环境变暖的巨大潜力。本研究旨在探讨 2-BP 在妊娠第 6-17 天经母体暴露对 ICR 小鼠孕鼠及其胚胎-胎儿发育的潜在不良影响。测试化学物质以 500、1000 和 1500mg/kg/天的剂量经皮下给予妊娠小鼠。所有孕鼠均在妊娠第 18 天行剖宫产术,检查其胎儿的外部、内脏和骨骼异常。在整个研究期间,未在接受 2-BP 治疗的各组中发现与治疗相关的死亡。1000 和 1500mg/kg 组的妊娠小鼠出现与治疗相关的临床症状,如皮毛粗糙、注射部位肿胀、硬结、结痂和溃疡,其发生率和严重程度呈剂量依赖性。在 1500mg/kg/天的剂量下,胎儿体重减轻、胎儿畸形增加和胎儿骨化延迟增加呈剂量依赖性。相反,在任何测试剂量下,体重、体重增加、妊娠子宫重量、食物消耗、大体观察均无不良影响。此外,未观察到黄体数、植入数、吸收率、死胎数、活胎数和活胎性别比与治疗有关的影响。这些发现表明,2-BP 在 ICR 小鼠中以最小的母体毒性剂量(即 1500mg/kg/天)具有胚胎毒性和致畸性。在本实验条件下,2-BP 的无观察不良效应水平分别为母体 500mg/kg/天和胎儿 1000mg/kg/天。

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