Gagnaire F, Marignac B
Department of Industrial and Experimental Toxicology, National Institut for Research and Safety, Vandoeuvre, France.
Pharmacol Toxicol. 1999 Jun;84(6):247-54. doi: 10.1111/j.1600-0773.1999.tb01490.x.
Motor and sensory conduction velocities and amplitudes of the sensory and motor action potentials of the tail nerve were studied in male Sprague-Dawley rats during subchronic oral treatment with three unsaturated aliphatic nitriles. The rats were given, by gastric intubation, doses of 10, 20 and 40 mg x kg(-1) 3-butenenitrile (allyl cyanide) and 25, 50 and 100 mg x kg(-1) of either cis/trans-2-butenenitrile (crotononitrile) or cis-2-pentenenitrile once a day, 5 days per week for 12 weeks. Moreover, 3,3'-iminodipropionitrile was administered likewise at doses of 25, 50 and 100 mg x kg(-1) as reference neurotoxicant. Oral administration of the three unsaturated nitriles produced deafness and absence of reaction when the animals were subject to droptest. Moreover, rats exhibited both time- and concentration-dependent decreases in motor and sensory conduction velocities and amplitudes of the sensory action potentials. Nerve conduction velocities were partially reversible after 8 weeks of recovery. Rats receiving 3,3'-iminodipropionitrile developed deafness, head weaving and significant irreversive deficiencies in all the electrophysiological parameters studied. Further toxicological studies with related unsaturated nitriles should be carried out to determine the potential importance of the cis/trans isomerism in the observed neurotoxicity.
在雄性Sprague-Dawley大鼠亚慢性口服三种不饱和脂肪腈期间,研究了尾神经的运动和感觉传导速度以及感觉和运动动作电位的幅度。通过胃插管,给大鼠每日一次给予剂量为10、20和40mg·kg⁻¹的3-丁烯腈(烯丙基氰)以及25、50和100mg·kg⁻¹的顺式/反式-2-丁烯腈(巴豆腈)或顺式-2-戊烯腈,每周5天,共12周。此外,以25、50和100mg·kg⁻¹的剂量同样给予3,3'-亚氨基二丙腈作为参考神经毒剂。口服这三种不饱和腈会导致动物在进行滴耳试验时出现耳聋和无反应。此外,大鼠的运动和感觉传导速度以及感觉动作电位的幅度均呈现出时间和浓度依赖性降低。恢复8周后,神经传导速度部分可逆。接受3,3'-亚氨基二丙腈的大鼠出现耳聋、头部摆动,并且在所有研究的电生理参数方面存在明显的不可逆缺陷。应使用相关不饱和腈进行进一步的毒理学研究,以确定顺式/反式异构现象在观察到的神经毒性中的潜在重要性。