Acute toxicity of some synthetic cyanogens in rats: Time-dependent cyanide generation and cytochrome oxidase inhibition in soft tissues after sub-lethal oral intoxication

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 (1 h) < PCN ≈ ACN (8 h) < SCN (24 h) < 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.