| 독성 요약 | IDENTIFICATION: Other cyanides, such as sodium and potassium cyanide, are solid or crystalline hygroscopic salts widely used in ore extracting processes for the recovery of gold and silver, electroplating, case-hardening of steel, base metal flotation, metal degreasing, dyeing, printing, and photography. They are also widely used in the synthesis of organic and inorganic chemicals (e.g., nitriles, carboxylic acids, amides, esters, and aminesheavy metal cyanides) and in the production of chelating agents. HUMAN EXPOSURE: Cyanides are well absorbed via the gastrointestinal tract or skin and rapidly absorbed via the respiratory tract. Once absorbed, cyanide is rapidly and ubiquitously distributed throughout the body, although the highest levels are typically found in the liver, lungs, blood, and brain. There is no accumulation of cyanide in the blood or tissues following chronic or repeated exposure. Approximately 80% of absorbed cyanide is metabolized to thiocyanate in the liver by the mitochondrial sulfur transferase enzyme rhodanese and other sulfur transferases. Thiocyanate is excreted in the urine. Minor pathways for cyanide detoxification involve reaction with cystine to produce aminothiazoline- and iminothiazolidinecarboxylic acids and combination with hydroxycobalamin (vitamin B12a) to form cyanocobalamin (vitamin B12)these end-products are also excreted in the urine. The principal features of the toxicity profile for cyanide are its high acute toxicity by all routes of administration, with a very steep and rate-dependent dose-effect curve, and chronic toxicity, probably mediated through the main metabolite and detoxification product, thiocyanate. The toxic effects of cyanide ion in humans and animals are generally similar and are believed to result from inactivation of cytochrome oxidase and inhibition of cellular respiration and consequent histotoxic anoxia. The primary targets of cyanide toxicity in humans are the cardiovascular, respiratory, and central nervous systems. The endocrine system is also a potential target for long-term toxicity, as a function of continued exposure to thiocyanate, which prevents the uptake of iodine in the thyroid and acts as a goitrogenic agent. Sequele after severe acute intoxications may include neuropsychiatric manifestations and Parkinson-type disease. Cyanide from tobacco smoke has been implicated as a contributing factor in tobacco-alcohol amblyopia. Long-term exposure to lower concentrations of cyanide in occupational settings can result in a variety of symptoms related to central nervous system effects. Cyanides are weakly irritating to the skin and eyealkali salts have not been identified. ANIMAL/PLANT STUDIES: The principal features of the toxicity profile for cyanide are its high acute toxicity by all routes of administration, with a very steep and rate-dependent dose-effect curve, and chronic toxicity, probably mediated through the main metabolite and detoxification product, thiocyanate. The toxic effects of cyanide ion in humans and animals are generally similar and are believed to result from inactivation of cytochrome oxidase and inhibition of cellular respiration and consequent histotoxic anoxia. The primary targets of cyanide toxicity in animals are the cardiovascular, respiratory, and central nervous systems. The endocrine system is also a potential target for long-term toxicity, as a function of continued exposure to thiocyanate, which prevents the uptake of iodine in the thyroid and acts as a goitrogenic agent. In a 13-week repeated-dose toxicity study in which cyanide was administered in drinking-water, there were no clinical signs associated with central nervous system effects or histopathological effects in the brain or thyroid of rats or mice. There were slight changes in the reproductive tract in male rats, which, although they apparently would not affect fertility in rats. The examination of neurotoxicity in this study was limited to clinical observation and optical microscopy in autopsy. The few available studies specifically intended to investigate neurotoxicity, while reporting adverse effects at exposure levels of 1.2 mg cyanide/kg body weight per day in rats and 0.48 mg cyanide/kg body weight per day in goats, suffer from weaknesses that preclude their quantitative assessment. In relation to characterization of concentration-response for repeated-dose toxicity for inhalation (relevant principally to the occupational environment), in three separate studies in rats, there were no adverse systemic effects in rats exposed to acetone cyanohydrin, which is rapidly hydrolysed to hydrogen cyanide at physiological pH, at concentrations up to 211 mg/m3 (corresponding to a concentration of 67 mg hydrogen cyanide/m3). The steepness of the dose-effect curve is illustrated by the observation of 30% mortality among rats exposed part of the day to 225 mg acetone cyanohydrin/m3 (71 mg hydrogen cyanide/m3). Adverse effects of exposure to the low concentrations of cyanide that are generally present in the general environment (<1 ug/m3 in ambient air<10 ug/litre in water) are unlikely. /Cyanide/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) |
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