Evaluation of the developmental toxicity of formamide in Sprague-Dawley (CD) rats.
Evaluation of the developmental toxicity of formamide in Sprague-Dawley (CD) rats.
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评估甲酰胺对 Sprague-Dawley (CD) 大鼠的发育毒性。
DOI：
10.1093/toxsci/57.2.284
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Jahnke,GD
中科院分区：
文献类型：
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作者：
George,JD;Price,CJ;Marr,MC;Myers,CB;Jahnke,GD
定时妊娠CD®远系白化病Sprague-Dawley大鼠在妊娠第6 - 19天（gd）接受甲酰胺（50、100或200 mg/kg/天）或溶媒（5 ml/kg去离子/蒸馏水，po）。在整个妊娠期间定期监测母体摄食量和饮水量（绝对和相对）、体重和临床体征。在处死时（gd 20），评价确认妊娠的雌性动物（每组21-23只）的临床状态和妊娠结局;检查活胎的外部、内脏和骨骼畸形和变异。无母体死亡，也无剂量相关临床体征。在200 mg/kg/天剂量下，gd 20的母体体重、体重增量和妊娠子宫重量显著降低。经妊娠子宫重量、肝脏重量（绝对或相对）以及摄食量和饮水量（绝对或相对）校正的母体体重增加不受影响。甲酰胺不影响产前活力或胎儿畸形或变异的发生率。100和200 mg/kg/天剂量组的平均胎仔体重/窝降低。与先前发表的研究相比，在较低的日剂量下，胎仔体重受到影响，这可能是由于总暴露期较长和/或停止暴露与终止之间缺乏恢复期。总之，在本研究条件下，母体毒性无明显不良作用水平（NOAEL）为100 mg/kg/天，低可见不良作用水平（LOAEL）为200 mg/kg/天。同样，发育毒性NOAEL为50 mg/kg/天，LOAEL为100 mg/kg/天。
Timed-pregnant CD® outbred albino Sprague-Dawley rats received formamide (50, 100, or 200 mg/kg/day) or vehicle (5 ml/kg deionized/distilled water, po) on gestational days (gd) 6 through 19. Maternal food and water consumption (absolute and relative), body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20), confirmed-pregnant females (21–23 per group) were evaluated for clinical status and gestational outcome; live fetuses were examined for external, visceral, and skeletal malformations and variations. There were no maternal deaths and no dose-related clinical signs. At 200 mg/kg/day, maternal body weight on gd 20, weight gain, and gravid uterine weight were significantly decreased. Maternal weight gain, corrected for gravid uterine weight, liver weight (absolute or relative), and food and water consumption (absolute or relative), were not affected. Formamide did not affect prenatal viability or incidences of fetal malformations or variations. Average fetal body weight/litter was decreased at 100 and 200 mg/kg/day. Fetal body weight was affected at lower daily doses than in previously published studies, possibly due to the longer total exposure period and/or lack of a recovery period between cessation of exposure and termination. In summary, the maternal toxicity no-observed-adverse-effect level (NOAEL) was 100 mg/kg/day and the low observed adverse effect level (LOAEL) was 200 mg/kg/day under the conditions of this study. Similarly, the developmental toxicity NOAEL was 50 mg/kg/day and the LOAEL was 100 mg/kg/day.