This class of compounds is characterized by the presence of a C=N (cyano) group and includes the cyanides and nitriles (R–C=N) as well as related chemicals such as cyanogens, isocyanates and cyanamides. They primarily owe their toxicity to the cyanide ion, which is capable of inhibiting many enzymes, especially cytochrome oxidase, when released in the body. Death, which may be more or less rapid depending on the rate at which the cyanide ion is released, results from chemical asphyxia at the cellular level.
Inorganic Cyanides
Inorganic cyanides are readily hydrolyzed by water and decomposed by carbon dioxide and mineral acids to form hydrogen cyanide, which can also be produced by certain naturally occurring bacteria. Hydrogen cyanide is evolved in coke and steel-making, and can be generated in fires where polyurethane foam is incinerated (e.g., furniture, partitions and so on). It can be generated accidentally by the action of acids on cyanide-containing wastes (lactonitrile evolves hydrocyanic acid when in contact with an alkali, for example.), and intentionally in gas chambers for capital punishment, where cyanide pellets are dropped into bowls of acid to create a lethal atmosphere.
Nitriles
Nitriles (also called organic cyanides) are organic compounds which contain a cyano group
(–C=N) as the characteristic functional group and have the generic formula RCN. They may be regarded as hydrocarbon derivatives wherein three hydrogen atoms attached to a primary carbon are replaced by a nitrilo group, or as derivatives of carboxylic acids (R—COOH) in which the oxo and hydroxyl radicals are replaced by a nitrilo group (R—C=N). Upon hydrolysis, they yield an acid which contains the same number of carbon atoms and which, therefore, is usually named by analogy with the acid rather than as a derivative of hydrogen cyanide. They are very dangerous when heated to decomposition because of the release of hydrogen cyanide.
Saturated aliphatic nitriles up to C14 are liquids having a rather pleasant odour like the ethers. Nitriles of C14 and higher are odourless solids and generally colourless. Most nitriles will boil without decomposition at temperatures lower than those for the corresponding acids. They are extremely reactive compounds and are used extensively as intermediates in organic synthesis. They are widely used starting materials in the synthesis of various fatty acids, pharmaceuticals, vitamins, synthetic resins, plastics and dyes.
Uses
The inorganic cyano compounds have varied uses in the metal, chemical, plastics and rubber industries. They are utilized as chemical intermediates, pesticides, metal cleaners, and as agents for extracting gold and silver from ores.
Acryonitrile (vinyl cyanide, cyanoethylene, propene nitrile), a flammable and explosive colourless liquid, is found in surface coatings and adhesives and is used as a chemical intermediate in the synthesis of antioxidants, pharmaceuticals, pesticides, dyes and surface-active agents.
Calcium cyanamide (nitrolim, calcium carbimide, cyanamide) is a blackish-grey, shiny powder used in agriculture as a fertilizer, herbicide, pesticide and a defoliant for cotton plants. It is also used in steel hardening and as a desulphurizer in the iron and steel industry. In industry, calcium cyanamide is used for the manufacture of calcium cyanide and dicyandiamide, the raw material for melamine.
Cyanogen, cyanogen bromide and cyanogen chloride are used in organic syntheses. Cyanogen is also a fumigant and a fuel gas for welding and cutting heat-resistant metals. It is a rocket or missile propellant in mixtures with ozone or fluorine; and it may also be present in blast furnace emissions. Cyanogen bromide is utilized in textile treatment, as a fumigant and pesticide, and in gold extraction processes. Cyanogen chloride serves as a warning agent in fumigant gases.
Hydrogen cyanide finds use in the manufacture of synthetic fibres and plastics, in metal polishes, electroplating solutions, metallurgical and photographic processes, and in the production of cyanide salts. Sodium cyanide and potassium cyanide are used in electroplating, steel hardening, extraction of gold and silver from ores, and in the manufacture of dyes and pigments. In addition, sodium cyanide functions as a depressant in the froth flotation separation of ores.
Potassium ferricyanide (red prussiate of potash) is used in photography and in blueprints, metal tempering, electroplating and pigments. Potassium ferrocyanide (yellow prussiate of potash) is used in the tempering of steel and in process engraving. It is employed in the manufacture of pigments and as a chemical reagent.
Calcium cyanide, malononitrile, acetone cyanohydrin (2-hydroxy-2-methylproprionitrile), cyanamide and acrylonitrile are other useful compounds in the metal, plastics, rubber and chemical industries. Calcium cyanide and malononitrile are leaching agents for gold. In addition, calcium cyanide is used as a fumigant, a pesticide, a stabilizer for cement, and in the manufacture of stainless steel. Acetone cyanohydrin is a complexing agent for metal refining and separation, and cyanamide is used in metal cleaners, the refining of ores and the production of synthetic rubber. Ammonium thiocyanate is used in the match and photography industries and for double-dyeing fabrics and improving the strength of silks weighted with tin salts. It is a stabilizer for glues, a tracer in oil fields, and an ingredient in pesticides and liquid rocket propellants. Potassium cyanate serves as a chemical intermediate and as a weed killer.
Some of the more important organic nitriles in industrial use include acryonitrile (vinyl cyanamide, cyanethylene, propene nitrile), acetonitrile, (methyl cyanamide, ethanenitrile, cyanomethane), ethylene cyanohydrin, proprionitrile (ethyl cyanide), lactonitrile, glycolonitrile (formaldehyde cyanohydrin, hydroxyacetonitrile, hydroxymethylcyanide, methylene cyanohydrin), 2-methyl-lactonitrile, and adiponitrile.
Hazards
Cyanide compounds are toxic to the extent that they release the cyanide ion. Acute exposure can cause death by asphyxia, as the result of exposure to lethal concentrations of hydrogen cyanide (HCN) whether by inhalation, ingestion or percutaneous absorption; in the last case, however, the dose required is higher. Chronic exposure to cyanides at levels too low to produce such serious symptoms may cause a variety of problems. Dermatitis, often accompanied by itching, an erythematous rash and papules, has been a problem for workers in the electroplating industry. Severe irritation of the nose may lead to obstruction, bleeding, sloughs and, in some cases, perforation of the septum. Among fumigators, mild cyanide poisoning has been recognized as the cause of symptoms of oxygen starvation, headache, rapid heart rate, and nausea, all of which were completely reversed when the exposure ceased.
Chronic systemic cyanide poisoning may occur, but is rarely recognized because of the gradual onset of the disability, and symptoms which are consistent with other diagnoses. It has been suggested that excessive thiocyanate in extracellular fluids might explain chronic illness due to cyanide, since the symptoms reported are similar to those found when thiocyanate is used as a drug. Symptoms of chronic disease have been reported in electroplaters and silver polishers after several years of exposure. The most prominent were motor weakness of arms and legs, headaches and thyroid diseases; these findings have also been reported as complications of thiocyanate therapy.
Toxicity
Cyanides
The cyanide ion of soluble cyanide compounds is rapidly absorbed from all routes of entry—inhalation, ingestion and percutaneous. Its toxic properties result from its ability to form complexes with heavy metal ions which inhibit the enzymes required for cellular respiration, primarily cytochrome oxidase. This prevents the uptake of oxygen by the tissues, causing death by asphyxia. The blood retains its oxygen, producing the characteristic cherry-red colour of the victims of acute cyanide poisoning. Cyanide ions combine with the approximately 2% of methaemoglobin normally present—a fact that has helped to develop the treatment of cyanide poisoning.
If the initial dose is not fatal, part of the cyanide dose is exhaled unchanged, while rhodanase, an enzyme widely distributed in the body, converts the remainder to the much less harmful thiocyanate, which remains in extracellular body fluids until it is excreted in the urine. Urinary levels of thiocyanate have been used to measure the extent of the intoxication, but they are non-specific and are elevated in smokers. There may be an effect on thyroid function due to the affinity of thiocyanate ion for iodine.
There are variations in the biological effects of the compounds in this group. At low concentrations, hydrogen cyanide (hydrocyanic acid, prussic acid) and the halogenated cyanide compounds (i.e., cyanogen chloride and bromide) in vapour form produce irritation of the eyes and the respiratory tract (the respiratory effects, including pulmonary oedema, may be delayed). Systemic effects include weakness, headaches, confusion, nausea and vomiting. In mild cases, the blood pressure remains normal despite increase in the pulse rate. The respiratory rate varies with the intensity of exposure—rapid with mild exposure, or slow and gasping with severe exposure.
Nitriles
The toxicity of nitriles varies greatly with their molecular structure, ranging from comparatively non-toxic compounds (e.g., the saturated fatty acid nitriles) to highly toxic materials, such as α-aminonitriles and α-cyanohydrins, which are considered to be as toxic as hydrocyanic acid itself. The halogenated nitriles are highly toxic and irritant, and cause considerable lacrimation. Nitriles such as acrylonitrile, propionitrile and fumaronitrile are toxic and may cause severe and painful dermatitis in exposed skin.
Exposure to toxic nitriles may rapidly cause death by asphyxiation similar to that resulting from exposure to hydrogen cyanide. Individuals who survived exposure to high concentrations of nitriles were said to have no evidence of residual physiological effects after the recovery from the acute episode; this has led to the opinion that the person either succumbs to the nitrile exposure or recovers completely.
Medical surveillance should include pre-employment and periodic examinations focused on skin disorders and the cardiovascular, pulmonary and central nervous systems. A history of fainting spells or convulsive disorders might present an added risk for nitrile workers.
All nitriles should be handled under carefully controlled conditions and only by personnel having a thorough understanding and knowledge of safe handling techniques. Leather should not be used for protective garments, gloves and footwear, since it may be penetrated by acryonitrile and other similar compounds; rubber protective equipment should be washed and inspected frequently to detect swelling and softening. The eyes should be protected, proper respirators worn, and all splashes immediately and thoroughly washed away.
Acrylonitrile. Acrylonitrile is a chemical asphyxiant like hydrogen cyanide. It is also an irritant, affecting the skin and mucous membranes; it may cause severe corneal damage in the eye if not rapidly washed away by copious irrigation. IARC has classified acrylonitrile as a Group 2A carcinogen: the agent is probably carcinogenic to humans. The classification is based on limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in animals.
Acrylonitrile may be absorbed by inhalation or through the skin. In gradual exposures, victims may have significant levels of cyanide in the blood before symptoms appear. They derive from tissue anoxia and include, roughly in order of onset, limb weakness, dyspnoea, burning sensation in the throat, dizziness and impaired judgement, cyanosis and nausea. In the later stages, collapse, irregular breathing or convulsions and cardiac arrest may occur without warning. Some patients appear hysterical or may even be violent; any such deviations from normal behaviour should suggest acryonitrile poisoning.
Repeated or prolonged skin contact with acrylonitrile may produce irritation after hours of no apparent effect. Since acrylonitrile is readily absorbed into leather or clothing, blistering may appear unless the contaminated articles are removed promptly and the underlying skin washed. Rubber clothing should be inspected and washed frequently because it will soften and swell.
An important hazard is fire and explosion. The low flashpoint indicates that sufficient vapour is evolved at normal temperatures to form a flammable mixture with air. Acrylonitrile has the ability to polymerize spontaneously under the action of light or heat, which may lead to explosion even when it is kept in closed containers. It must therefore never be stored uninhibited. The danger of fire and explosion is intensified by the lethal nature of the fumes and vapours evolved, such as ammonia and hydrogen cyanide.
Calcium cyanamide. Calcium cyanamide is encountered chiefly as a dust. When inhaled, it will cause rhinitis, pharyngitis, laryngitis and bronchitis. Perforation of the nasal septum has been reported after long exposure. In the eyes, it may cause conjunctivitis, keratitis and corneal ulceration. It may cause an itchy dermatitis which, after a time, may present slowly-healing ulcerations on the palms of the hand and between the fingers. Skin sensitization may occur.
Its most notable systemic effect is a characteristic vasomotor reaction featuring diffuse erythema of the body, face and arms which may be accompanied by fatigue, nausea, vomiting, diarrhoea, dizziness and sensations of cold. In severe cases, circulatory collapse may ensue. This vasomotor reaction may be triggered or exaggerated by consumption of alcohol.
In addition to adequate exhaust ventilation and personal protective equipment, a waterproof barrier cream may provide added protection for face and exposed skin. Good personal hygiene, including showers and changes of clothing after each shift, is important.
Cyanates. Some of the more important cyanates in industrial use include sodium cyanate, potassium cyanate, ammonium cyanate, lead cyanate and silver cyanate. Cyanates of such elements as barium, boron, cadmium, cobalt, copper, silicon, sulphur and thallium may be prepared by reactions between solutions of a cyanate and the corresponding salt of the metal. They are dangerous because they release hydrogen cyanide when heated to decomposition or when in contact with acid or acid fumes. Personnel handling these materials should be provided with respiratory and skin protection.
Sodium cyanate is used in organic synthesis, the heat treatment of steel, and as an intermediate in the manufacture of pharmaceuticals. It is considered to be moderately toxic, and workers should be protected against dust inhalation and skin contamination.
Cyanate compounds vary in toxicity; therefore, they should be handled under controlled conditions, taking standard precautions to protect personnel against exposure. When heated to decomposition or when placed in contact with acid or acid fumes, the cyanates emit highly toxic fumes. Adequate ventilation must be provided, and air quality at the worksite should be closely monitored. Personnel should not inhale contaminated air nor allow skin contact with these materials. Good personal hygiene is essential for those working in areas where such compounds are handled.
Safety and Health Measures
Scrupulous attention to proper ventilation is necessary. Complete enclosure of the process is recommended, with supplementary exhaust ventilation available. Warning signs should be posted near entrances to areas in which hydrogen cyanide may be released into the air. All shipping and storage containers for hydrogen cyanide or cyanide salts should bear a warning label that included instructions for first aid; they should be in a well-ventilated area and handled with great care.
Those working with cyanide salts should fully understand the hazard. They should be trained to recognize the characteristic odour of hydrogen cyanide and to evacuate the work area immediately if it is detected. Workers entering a contaminated area must be supplied with air-supplied or self-contained respirators with canisters specific for cyanides, goggles if full-face masks are not worn, and impervious protective clothing.
For those who work with acrylonitrile, the usual precautions for carcinogens and for highly flammable liquids are necessary. Steps must be taken to eliminate the risk of ignition from sources such as electrical equipment, static electricity and friction. Because of the toxic, as well as the flammable, nature of the vapour, its escape into the worksite air must be prevented by enclosure of the process and exhaust ventilation. Continuous monitoring of the workplace air is necessary to ensure that these engineering controls remain effective. Personal respiratory protection, preferably of the positive pressure type, and impermeable protective clothing are necessary when there is a possibility of exposure, as from a normal but non-routine operation such as a pump replacement. Leather should not be used for protective clothing since it is readily penetrated by acrylonitrile; rubber and other types of clothing should be inspected and washed frequently.
Acrylonitrile workers should be educated about the chemical’s dangers and trained in rescue, decontamination, life-support procedures and the use of amyl nitrate. Skilled medical attention is required in emergencies; principal requirements are an alarm system and plant personnel trained to support the activities of the health professionals. Supplies of specific antidotes should be available on site and at adjacent hospital centres.
Medical surveillance of workers potentially exposed to cyanides should focus on the respiratory, cardiovascular and central nervous systems; liver, kidney and thyroid function; condition of the skin; and a history of fainting or dizzy spells. Workers with chronic diseases of the kidneys, respiratory tract, skin or thyroid are at greater risk of developing toxic cyanide effects than healthy workers.
Medical control requires training in artificial resuscitation and the use of drugs prescribed for emergency treatment of acute poisoning (e.g., inhalations of amyl nitrite). As soon as possible, contaminated clothing, gloves and footwear should be removed and the skin washed to prevent continuing absorption. First-aid kits with drugs and syringes should be placed appropriately at hand and checked frequently.
Unfortunately, some widely distributed handbooks suggest that methylene blue is useful in cyanide poisoning because, at certain concentrations, it forms methaemoglobin, which, because of its affinity for the cyanide ion, might reduce the toxic effect. The use of methylene blue is not recommended since at other concentrations it has the reverse effect of converting methaemoglobin to haemoglobin, and analyses to verify that its concentration is appropriate are not feasible under the conditions created by the cyanide emergency.
Treatment
Individuals exposed to toxic levels of nitriles should be immediately removed to a safe area and given amyl nitrite by inhalation. Any indications of respiratory problems would indicate oxygen inhalation and, if necessary, cardiopulmonary resuscitation. Contaminated clothing should be removed and the areas of skin copiously washed. Extended flushing of the eyes with neutral solutions or water is advised if there is lacrimation or any evidence of conjunctival irritation. Properly trained physicians, nurses and emergency medical technicians should be summoned to the scene promptly to administer definitive treatment and keep the victim under close observation until recovery is complete.
Cyano compounds tables
Table 1 - Chemical information.
Table 2 - Health hazards.
Table 3 - Physical and chemical hazards.
Table 4 - Physical and chemical properties.