Tassinari M S, Mullenix P J, Moore P A
Toxicol Ind Health. 1986 Sep;2(3):261-71. doi: 10.1177/074823378600200305.
Recent evidence has indicated that the anesthetic gas nitrous oxide (N2O) is teratogenic to rats if exposed during the organogenesis phase of gestation. Little is known, however, of the anatomical or functional consequences of exposures occurring later in gestation when the brain is developing. Timed pregnant Sprague-Dawley rats were exposed to 75% N2O/25% O2 using one of the following protocols: 24 hr exposures on gestational days 11-15 or 16-20; or 8 hr exposures on gestational days 9-13, 11-15, 14-15 or day 15 only. Both 24 hr exposure protocols significantly reduced fetal and maternal body weight, an effect not observed after the 8 hr exposures. No N2O exposure resulted in gross morphological or skeletal changes. Likewise, no significant effects on total protein and DNA levels in fetal liver and brain tissues could be found subsequent to 24 hr exposures on days 16-20; or on one, three or six days following an 8 hr exposure on day 15. Evaluations of postnatal growth and neurological development in pups prenatally exposed for 8 hr on days 14 and 15 revealed two noteworthy effects. Their rate of growth in body weight was greater with respect to controls between the ages of 14 and 21 days, especially in the males. Also, reflex suspension was reduced, significantly so in the females. In conclusion, unlike 24 hr exposures, multiple 8 hr exposures to nitrous oxide during the middle to late stages of gestation did not produce effects detectable with standard teratological measures. Subtle differences in growth rate and reflex suspension, however, indicated that normal development had been interrupted, but its clear distinction as a lasting effect requires additional measures of function.
近期有证据表明，麻醉气体氧化亚氮（N₂O）若在妊娠期的器官形成阶段暴露，会对大鼠产生致畸作用。然而，对于在妊娠期大脑发育阶段后期暴露所产生的解剖学或功能后果，人们却知之甚少。将定时受孕的斯普拉格 - 道利大鼠按照以下方案之一暴露于75% N₂O/25% O₂环境中：在妊娠第11 - 15天或16 - 20天进行24小时暴露；或在妊娠第9 - 13天、11 - 15天、14 - 15天或仅在第15天进行8小时暴露。两种24小时暴露方案均显著降低了胎儿和母体体重，而8小时暴露后未观察到这种效应。没有N₂O暴露导致明显的形态或骨骼变化。同样，在妊娠第16 - 20天进行24小时暴露后；或在第15天进行8小时暴露后的1天、3天或6天，均未发现对胎儿肝脏和脑组织中的总蛋白和DNA水平有显著影响。对在第14天和15天产前暴露8小时的幼崽进行出生后生长和神经发育评估，发现了两个值得注意的效应。在14至21日龄期间，它们的体重增长速度相对于对照组更快，尤其是雄性。此外，反射悬垂减少，雌性尤为显著。总之，与24小时暴露不同，在妊娠中后期多次8小时暴露于氧化亚氮并未产生标准致畸学测量可检测到的效应。然而，生长速度和反射悬垂的细微差异表明正常发育已被中断，但其作为持久效应的明确区分需要额外的功能测量。
