Young J F, Gough B J, Suber R L, Gaylor D W
National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079-9502, USA.
J Toxicol Environ Health A. 2001 Feb 9;62(3):161-74. doi: 10.1080/009841001458280.
The dose-mortality response curve for sarin when administered to pregnant rats is extremely steep. The pregnant animal either died during the treatment or survived with no observable fetal toxicity. Animals that died displayed many symptoms characteristic of anticholinesterase toxicity. The present study was conducted to determine whether the maternal deaths, clinical observations, and/or weight loss could be correlated with baseline blood cholinesterase levels in individual animals. Cholinesterase levels (plasma and erythrocyte) were obtained prior to, during, and following treatment of nonpregnant rats by gavage with 380 microg/kg/d sarin for 10 d. After the first dose, there was a drop in the plasma cholinesterase levels, which then remained low throughout the dosing period. There was a statistically significant correlation between body weight loss and plasma cholinesterase levels of the sarin dosed animals. The surviving animals also had lower plasma cholinesterase levels and lower body weights, both of which recovered on the cessation of dosing. The erythrocyte cholinesterase levels were not different between treated and nontreated rats. Neither plasma or erythrocyte baseline cholinesterase levels nor relative or absolute cholinesterase decline values could be used as predictors of mortality from sarin administration in rats.
给怀孕大鼠施用沙林时的剂量-死亡率反应曲线极为陡峭。怀孕动物要么在治疗期间死亡，要么存活下来且未观察到胎儿毒性。死亡的动物表现出许多抗胆碱酯酶毒性的特征症状。本研究旨在确定母体死亡、临床观察结果和/或体重减轻是否与个体动物的基线血胆碱酯酶水平相关。在非怀孕大鼠通过灌胃给予380微克/千克/天沙林持续10天的治疗之前、期间和之后，获取胆碱酯酶水平（血浆和红细胞）。首次给药后，血浆胆碱酯酶水平下降，然后在整个给药期间一直保持在低水平。沙林给药动物的体重减轻与血浆胆碱酯酶水平之间存在统计学上的显著相关性。存活的动物血浆胆碱酯酶水平也较低，体重也较轻，两者在停药后均恢复。处理过的大鼠和未处理的大鼠之间红细胞胆碱酯酶水平没有差异。血浆或红细胞基线胆碱酯酶水平以及相对或绝对胆碱酯酶下降值均不能用作大鼠沙林给药死亡率的预测指标。
