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孕期暴露于环境污染物2-溴丙烷对大鼠胚胎-胎儿发育的影响。

Effects of prenatal exposure to the environmental pollutant 2-bromopropane on embryo-fetal development in rats.

作者信息

Kim Jong-Choon, Kim Sung-Ho, Shin Dong-Ho, Ahn Tae-Ho, Kim Hyoung-Chin, Kim Yun-Bae, Jiang Cheng-Zhe, Han Junghee, Chung Moon-Koo

机构信息

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

出版信息

Toxicology. 2004 Mar 1;196(1-2):77-86. doi: 10.1016/j.tox.2003.11.006.

Abstract

2-Bromopropane (2-BP), a halogenated propane analogue, is a substitute for chlorofluorocarbones. 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 on gestational days (GD) 6 through 19 in Sprague-Dawley rats. The test chemical was administered subcutaneously to pregnant rats at dose levels of 0, 250, 500, and 1000 mg/kg per day. All dams were subjected to caesarean section on GD 20 and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1000 mg/kg group, maternal toxicity included an increase in the incidence of abnormal clinical signs, a suppression in the body weight and body weight gain, and a decrease in the food intake. Developmental toxicity included an increase in the fetal deaths, a decrease in the litter size, and a reduction in the fetal body weight. In addition, an increase in the incidence of fetal external, visceral, and skeletal abnormalities was seen. In the 500 mg/kg group, minimal developmental toxicity including decreased fetal body weight and increased fetal ossification delay was observed. There were no adverse effects on either pregnant dams or embryo-fetal development in the 250 mg/kg group. These findings suggest that a 14-day subcutaneous dose of 2-BP is embryotoxic and teratogenic at a maternally toxic dose (i.e., 1000 mg/kg per day) and is minimally embryotoxic at a nonmaternally toxic dose (i.e., 500 mg/kg per day) in Sprague-Dawley rats. In the present experimental conditions, the no-observed-adverse-effect level (NOAEL) of 2-BP is considered to be 500 mg/kg per day for dams and 250 mg/kg per day for embryo-fetal development.

摘要

2-溴丙烷(2-BP)是一种卤代丙烷类似物,是氯氟烃的替代品。本研究旨在调查2-BP对妊娠母鼠的潜在不良影响,以及在妊娠第6天至第19天母体接触后对胚胎-胎儿发育的影响。将受试化学品以每天0、250、500和1000 mg/kg的剂量皮下注射给妊娠大鼠。所有母鼠在妊娠第20天接受剖腹产,并检查其胎儿的外部、内脏和骨骼异常情况。在1000 mg/kg组中,母体毒性包括异常临床体征发生率增加、体重和体重增加受到抑制以及食物摄入量减少。发育毒性包括胎儿死亡增加、窝仔数减少和胎儿体重减轻。此外,还观察到胎儿外部、内脏和骨骼异常的发生率增加。在500 mg/kg组中,观察到最小的发育毒性,包括胎儿体重下降和胎儿骨化延迟增加。250 mg/kg组对妊娠母鼠或胚胎-胎儿发育均无不良影响。这些发现表明,在Sprague-Dawley大鼠中,14天皮下注射2-BP在母体毒性剂量(即每天1000 mg/kg)下具有胚胎毒性和致畸性,在非母体毒性剂量(即每天500 mg/kg)下具有最小的胚胎毒性。在本实验条件下,2-BP对母鼠的无观察到不良影响水平(NOAEL)被认为是每天500 mg/kg,对胚胎-胎儿发育的NOAEL是每天250 mg/kg。

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