title: Acute toxicity of some synthetic cyanogens in rats: time-dependent cyanide generation and cytochrome oxidase inhibition in soft tissues after sub-lethal oral intoxication.
abstract: 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.
authors.affiliation: Pharmacology and Toxicology Division, Defence Research and Development Establishment, Gwalior, MP, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Rao
authors.forename: Poonam
authors.initials: P
authors.lastname: Singh
authors.forename: Shiv Kumar
authors.initials: SK
authors.lastname: Yadav
authors.forename: Niranjan L
authors.initials: NL
authors.lastname: Gujar
authors.forename: Rahul
authors.initials: R
authors.lastname: Bhattacharya
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D003486:Cyanides / Q000097:blood / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D053208:Kaplan-Meier Estimate; D007928:Lethal Dose 50; D009570:Nitriles / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D009599:Nitroprusside / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000506:poisoning*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013861:Thiocyanates / Q000652:urine; D014018:Tissue Distribution; D023382:Toxicity Tests, Acute; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000506:poisoning*
chemical_list: D003486:Cyanides; D004791:Enzyme Inhibitors; D009570:Nitriles; D013861:Thiocyanates; D014665:Vasodilator Agents; D009599:Nitroprusside; D003576:Electron Transport Complex IV; C031760:thiocyanate
keywords: ACN; ATCN; CNS; CYP; CYTOX; Cyanogenesis; Cyanogens; Cytochrome oxidase inhibition; MCN; PCN; SCN; SNP; Thiocyanate; acetonitrile; acrylonitrile; central nervous system; cytochrome P450; cytochrome oxidase; malononitrile; propionitrile; sodium nitroprusside; succinonitrile