HYDROGEN CYANIDE

Definition

Hydrogen cyanide (HCN); A toxic liquid or colorless gas. It is found in the smoke of various tobacco products and released by combustion of nitrogen-containing organic materials. Present in freshly distilled bitter almond oil (2-4%) prior to its removal by precipitation as calcium ferrocyanide to give food quality oil HCN is formed in Interstellar clouds through one of two major pathways: via a neutral-neutral reaction (CH2 + N ? HCN + H) and via dissociative recombination (HCNH+ + e- ? HCN + H). The dissociative recombination pathway is dominant by 30%; however, the HCNH+ must be in its linear form. Dissociative recombination with its structural isomer, H2NC+ produces hydrogen isocyanide (HNC), exclusively.; Hydrogen cyanide (with the historical common name of Prussic acid) is a chemical compound with chemical formula HCN. A solution of hydrogen cyanide in water is called hydrocyanic acid. Hydrogen cyanide is a colorless, extremely poisonous, and highly volatile liquid that boils slightly above room temperature at 26 °C (78.8 °F). HCN has a faint, bitter, almond-like odor that some people are unable to detect due to a genetic trait. Hydrogen cyanide is weakly acidic and partly ionizes in solution to give the cyanide anion, CN?. The salts of hydrogen cyanide are known as cyanides. HCN is a highly valuable precursor to many chemical compounds ranging from polymers to pharmaceuticals.; Hydrogen cyanide is a linear molecule, with a triple bond between carbon and nitrogen. It is a weak acid with a pKa of 9.2. A minor tautomer of HCN is HNC, hydrogen isocyanide.

Description

Hydrogen cyanide (with the historical common name of Prussic acid) is a chemical compound with chemical formula HCN. It is a colorless, extremely poisonous liquid that boils slightly above room temperature at 26 C (79ЎF). A hydrogen cyanide concentration of 300 mg/m3 in air will kill a human within 10Р60 minutes.[38] A hydrogen cyanide concentration of 3500 ppm (about 3200 mg/m3) will kill a human in about 1 minute.[38] The toxicity is caused by the cyanide ion, which halts cellular respiration by acting as a non-competitive inhibitor for an enzyme in mitochondria called cytochrome c oxidase.

Related Pathways

Hydrogen Cyanide Health Effects

General Information

Metabolism: Organic nitriles are converted into cyanide ions through the action of cytochrome P450 enzymes in the liver. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96)
Uses/Sources: Hydrogen cyanide is a precursor to many chemical compounds, ranging from polymers to pharmaceuticals. (L101)
Health Effects: Exposure to high levels of cyanide for a short time harms the brain and heart and can even cause coma, seizures, apnea, cardiac arrest and death. Chronic inhalation of cyanide causes breathing difficulties, chest pain, vomiting, blood changes, headaches, and enlargement of the thyroid gland. Skin contact with cyanide salts can irritate and produce sores. (L96, L97)
Symptoms: Cyanide poisoning is identified by rapid, deep breathing and shortness of breath, general weakness, giddiness, headaches, vertigo, confusion, convulsions/seizures and eventually loss of consciousness. (L96, L97)
Treatment: Antidotes to cyanide poisoning include hydroxocobalamin and sodium nitrite, which release the cyanide from the cytochrome system, and rhodanase, which is an enzyme occurring naturally in mammals that combines serum cyanide with thiosulfate, producing comparatively harmless thiocyanate. Oxygen therapy can also be administered. (L97)
Route of Exposure: Oral (L96) ; inhalation (L96) ; dermal (L96)

Toxicity

Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
Toxicity: LD50: 3700 ug/kg (Subcutaneous, Rat) (N010) LD50: 810 ug/kg (Intravenous, Rat) LD50: 3700 ug/kg (Oral, Mouse) LD50: 2990 ug/kg (Intraperitoneal, Mouse) LC50: 142 ppm over 30 minutes (Inhalation, Rat) (T32)
Lethal Dose: 50 to 60 mg (oral) or 270 ppm (inhaled for an adult human. (T37, T50)

Mechanism of Action

Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)

Target Name	Mechanism of Action	References
Glutathione reductase, mitochondrial	Cyanide inhibits glutathione reductase. (A76)	2734799
Tyrosinase	Cyanide inhibits tyrosinase. (A77)	16950829
Cytochrome c oxidase subunit 1 Cytochrome c oxidase subunit 2 Cytochrome c oxidase subunit 3 Cytochrome c oxidase subunit 4 isoform 1, mitochondrial Cytochrome c oxidase subunit 5A, mitochondrial Cytochrome c oxidase subunit 5B, mitochondrial Cytochrome c oxidase subunit 6A1, mitochondrial Cytochrome c oxidase subunit 6A2, mitochondrial Cytochrome c oxidase subunit 6B1 Cytochrome c oxidase subunit 6C Cytochrome c oxidase subunit 7A1, mitochondrial Cytochrome c oxidase subunit 7A2, mitochondrial Cytochrome c oxidase subunit 7B, mitochondrial Cytochrome c oxidase subunit 7C, mitochondrial Cytochrome c oxidase subunit 8A, mitochondrial Cytochrome c oxidase subunit 6B2 Cytochrome c oxidase subunit 4 isoform 2, mitochondrial Cytochrome c oxidase subunit 7B2, mitochondrial Cytochrome c oxidase subunit 8C, mitochondrial Putative cytochrome c oxidase subunit 7A3, mitochondrial	Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. (L97)
Succinate dehydrogenase cytochrome b560 subunit, mitochondrial Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial	Cyanide inhibits succinate dehydrogenases. (A76)	2734799
Alkaline phosphatase, tissue-nonspecific isozyme Alkaline phosphatase, placental-like	Cyanide inhibits alkaline phosphatases. (A73)	924371
Glutathione peroxidase 1 Glutathione peroxidase 2 Glutathione peroxidase 3 Phospholipid hydroperoxide glutathione peroxidase, mitochondrial Epididymal secretory glutathione peroxidase Glutathione peroxidase 6 Glutathione peroxidase 7 Probable glutathione peroxidase 8	Cyanide inhibits glutathione peroxidases. (A75)	7437059
Catalase	Cyanide inhibits catalase. (A74)	16728955
Superoxide dismutase [Cu-Zn] Extracellular superoxide dismutase [Cu-Zn]	Cyanide inhibits superoxide dismutase [Cu-Zn]. (A72)	15856906