Pharmacology and Toxicology Division, Defence Research and Development Establishment, Gwalior, MP, India.
Food Chem Toxicol. 2013 Sep;59:595-609. doi: 10.1016/j.fct.2013.06.035. Epub 2013 Jul 4.
Cyanogens include complex nitrile-containing compounds that can generate free cyanide of toxicological significance. Acute toxicity, time-dependent cyanide generation and cytochrome oxidase (CYTOX) inhibition in soft tissues, and urinary thiocyanate levels were measured after acute cyanogen intoxication in rats. Order of cyanogens in terms of LD₅₀ was: malononitrile (MCN)>propionitrile (PCN)≈sodium nitroprusside (SNP)>acrylonitrile (ACN)>succinonitrile (SCN)>acetonitrile (ATCN) for oral, and SNP>MCN>ACN>PCN>SCN>ATCN for intraperitoneal and subcutaneous routes. MCN was most toxic by oral (LD₅₀=66.4 mg/kg) and SNP by intraperitoneal (LD₅₀=16.7 mg/kg) and subcutaneous (LD₅₀=11.9 mg/kg) routes. Minimum survival time (25 min) was recorded after 4.0 LD₅₀ ATCN. Order of cyanogens (0.75 LD₅₀; oral) on the basis of maximum blood cyanide and time of peak cyanide generation were: ATCN>SNP>SCN>PCN>MCN>ACN, and MCN (30 min)<SNP (1h)<PCN≈ACN (8h)<SCN (24h)<ATCN (72 h), respectively. In most cases, time profile of cyanide generation correlated with corresponding CYTOX inhibition and urinary thiocyanate levels. With the understanding of time-dependent toxicity of different cyanogens, suitable therapeutic windows can be designed for their management.
氰化物包括复杂的含腈化合物，可产生具有毒理学意义的游离氰化物。在大鼠急性氰化物中毒后，测量了急性毒性、氰化物生成的时间依赖性、软组织细胞色素氧化酶（CYTOX）抑制作用和尿硫氰酸盐水平。根据 LD₅₀，氰化物的顺序为：丙二腈（MCN）>丙烯腈（PCN）≈硝普酸钠（SNP）>丙烯腈（ACN）>琥珀腈（SCN）>乙腈（ATCN）（口服），SNP>MCN>ACN>PCN>SCN>ATCN（腹腔内和皮下）。MCN 经口毒性最强（LD₅₀=66.4mg/kg），SNP 经腹腔内（LD₅₀=16.7mg/kg）和皮下（LD₅₀=11.9mg/kg）途径毒性最强。4.0LD₅₀ ATCN 后记录到最短存活时间（25 分钟）。根据最大血液氰化物和氰化物生成峰值时间，氰化物的顺序为（0.75LD₅₀；口服）：ATCN>SNP>SCN>PCN>MCN>ACN，MCN（30 分钟）<SNP（1 小时）<PCN≈ACN（8 小时）<SCN（24 小时）<ATCN（72 小时）。在大多数情况下，氰化物生成的时间谱与相应的 CYTOX 抑制作用和尿硫氰酸盐水平相关。随着对不同氰化物时间依赖性毒性的了解，可以为其管理设计合适的治疗窗口。
