Crowell J A, Parker R M, Bucci T J, Dacre J C
Pathology Associates, Inc., National Center for Toxicological Research, Jefferson, Arkansas 72079.
J Biochem Toxicol. 1989 Spring;4(1):15-20. doi: 10.1002/jbt.2570040104.
To estimate the potential of small doses of sarin (types I and II) and soman to cause delayed neuropathic effects, 400, 200, 61, and 0 micrograms/kg of sarin-I, 280, 140, 70, and 0 micrograms/kg of sarin-II, and 14.2, 7.1, 3.5, and 0 micrograms/kg of soman by gavage were compared with 510 mg/kg tri-o-cresyl phosphate (TOCP) in 14- to 18-month-old SPF white leghorn hens (4/dose) protected with atropine (100 mg/kg). The neuropathy target esterase (NTE) activity 24 hr after dosing was determined in brain, spinal cord, and lymphocytes and in plasma and brain for cholinesterase and carboxylesterase. None of the compounds showed statistically significant NTE decreases. Sarin-II showed a dose-related trend in the lymphocyte NTE (to 33% of control at 280 micrograms/kg), suggesting that longer exposure to lower doses might cause a cumulative neurotoxic insult. All of the agents decreased the activity of plasma and brain cholinesterase and carboxylesterase. Using more than 70% inhibition of brain NTE as a biochemical predictor of delayed neuropathy, sarin and soman appear unable to cause delayed neuropathy at nonlethal doses within this protocol.
为评估小剂量沙林（I型和II型）和梭曼导致迟发性神经病变效应的可能性，将经口给予14至18月龄无特定病原体（SPF）白来航母鸡（每个剂量组4只）400、200、61和0微克/千克的I型沙林、280、140、70和0微克/千克的II型沙林以及14.2、7.1、3.5和0微克/千克的梭曼与510毫克/千克的磷酸三邻甲苯酯（TOCP）进行比较，母鸡已预先用阿托品（100毫克/千克）进行保护。给药24小时后，测定脑、脊髓、淋巴细胞中的神经病靶酯酶（NTE）活性，以及血浆和脑中的胆碱酯酶和羧酸酯酶活性。所有化合物均未显示出具有统计学意义的NTE活性降低。II型沙林在淋巴细胞NTE活性方面呈现出剂量相关趋势（在280微克/千克时降至对照的33%），这表明长时间暴露于较低剂量可能会导致累积性神经毒性损伤。所有受试药剂均降低了血浆和脑胆碱酯酶及羧酸酯酶的活性。以脑NTE活性抑制超过70%作为迟发性神经病变的生化预测指标，在本实验方案下，沙林和梭曼在非致死剂量时似乎不会导致迟发性神经病变。
