Cyanide: Encyclopedia II - Cyanide - Toxicity

Cyanide - Toxicity

Cyanide - Absorption

The most usual route of absorption is by inhalation of hydrogen cyanide gas, which can be formed from alkaline cyanides and certain complex cyanides by the action of acid. Hydrogen cyanide poisoning is also common as a result of smoke inhalation after house fires.

Ingestion is equally dangerous, although this route of absorption is usually deliberate (suicidal or criminal). Absorption through the skin is also possible, though rare.

Cyanide - Mechanism of toxicity

Cyanide ions bind to the iron atom of the enzyme cytochrome c oxidase in the mitochondria of cells. This deactivates the enzyme and breaks the electron transport chain, meaning that the cell can no longer use the oxygen which is available to it.

Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.

Cyanide - Clinical symptoms

It is difficult to give dose figures in this section due to the rapid metabolism of cyanide in the human body. Animal studies are of little help, as different species have widely different sensitivities to cyanide: it is quite possible that there is also a considerable range of sensitivity among human individuals. The Regulatory information section below may give some guidance.

Inhalation of high concentrations of hydrogen cyanide causes a convulsive coma with apnea and cardiac arrest, with death following in a matter of minutes.

At lower doses, loss of consciousness may be preceded by headaches, vertigo and perceived difficulty in breathing. At the first stages of unconsciousness, breathing is often sufficient or even rapid, although the state of the victim progresses towards a deep coma, sometimes accompanied by pulmonary edema, and finally cardiac arrest.

At doses insufficient to cause rapid loss of consciousness, the most widely reported symptoms are vertigo, inebriety, confusion and a feeling of tightness around the chest.

The situation is complicated by the non-specific nature of the symptoms and by notoriety of the product. In many cases, such symptoms are psychosomatic, caused by anxiety at working with cyanides, and this is accentuated by the characteristic odor of hydrogen cyanide, detectable by healthy, undesensitized subjects at levels far below those which are believed to be toxic (odor threshold < 1 ppm). This is not to say that such symptoms should be taken lightly: if the patient is a truely a victim of cyanide poisoning, their clinical state may deteriorate rapidly; while if the symptoms are psychosomatic, they will surely reoccur unless the anxieties about the safety procedures are addressed.

Exposure to lower levels of cyanide over a long period (e.g., after use of cassava roots as a primary food source in tropical Africa) results in increased blood cyanide levels. These may result in weakness of the fingers and toes, difficulty walking, dimness of vision, deafness, and decreased thyroid gland function, but chemicals other than cyanide may contribute to these effects. Skin contact with cyanide can produce irritation and sores.

It is not known whether cyanides can directly cause birth defects in people. Birth defects were seen in rats that ate diets of cassava roots. Effects on the reproductive system were seen in rats and mice that drank water containing sodium cyanide.

Cyanide - Diagnosis of poisoning

There are medical tests to measure blood and urine levels of cyanide; however, small amounts of cyanide are not always detectable in blood and urine. Tissue levels of cyanide can be measured if cyanide poisoning is suspected, but cyanide is rapidly cleared from the body, so the tests must be done soon after the exposure. An almond-like odor in the breath may alert a doctor that a person was exposed to cyanide but not all people are able to smell HCN.

Cyanide - Treatment of poisoning and antidotes

The United States standard cyanide antidote kit first uses a small inhaled dose of amyl nitrite followed by intravenous sodium nitrite. This converts a portion of the hemoglobin's iron from ferrous iron to ferric iron, converting the hemoglobin into methemoglobin. Cyanide is more strongly drawn to methemoglobin than to the cytochrome oxidase of the cells, effectively pulling the cyanide off the cells and onto the methemoglobin. Once bound with the cyanide, the methemoglobin becomes cyanmethemoglobin. Therapy with nitrites is not innocuous. The doses given to an adult can potentially cause a fatal methemoglobinemia in children or may cause profound hypotension. Treatment of children affected with cyanide intoxication must be individualized and is based upon their body weight and hemoglobin concentration. The next part of the cyanide antidote kit is sodium thiosulfate, which is administered intravenously. The sodium thiosulfate and cyanmethemoglobin become thiocyanate, releasing the hemoglobin, and the thiocyanate is excreted by the kidneys.

Alternative methods of treating cyanide intoxication are used in other countries. For example, the method in France is to use hydroxycobalamin (a form of vitamin B₁₂), which combines with cyanide to form the harmless vitamin B_12a cyanocobalamin. Cyanocobalamin is eliminated through the urine. Hydroxycobalamin works both within the intravascular space and within the cells to combat cyanide intoxication. This contrasts with methemoglobin, which acts only within the vascular space as an antidote. Administration of sodium thiosulfate improves the ability of the hydroxycobalamin to detoxify cyanide poisoning. This treatment is considered so effective and innocuous that it is administered routinely in Paris to victims of smoke inhalation to detoxify any associated cyanide intoxication. However it is relatively expensive and not universally available.

4-Dimethylaminophenol (4-DMAP) has been proposed in Germany as a more rapid antidote than nitrites and with (reportedly) lower toxicity. It is used currently by the German military and by the civilian population. In humans, intravenous injection of 3 mg/kg of 4-DMAP will produce 35 percent methemoglobin levels within 1 minute. There are reports (de:4-Dimethylaminophenol), that 4-DMAP is part of the US Cyanokit, while it is not part of the GERM Cyanokit due to side effects (e. g. hemolysis).

Cobalt salts have also been demonstrated as effective in binding cyanide. One current cobalt-based antidote available in Europe is dicobalt-EDTA, sold as Kelocyanor®. This agent chelates cyanide as the cobalticyanide. This drug provides an antidote effect more quickly than formation of methemoglobin, but a clear superiority to methemoglobin formation has not been demonstrated. Cobalt complexes are quite toxic, and there have been accidents reported in the UK where patients have been given dicobalt-EDTA by mistake based on a false diagnoses of cyanide poisoning.

The International Programme on Chemical Safety issued a survey (IPCS/CEC Evaluation of Antidotes Series) which lists the following antidotal agents and their effects: Oxygen, sodium thiosulfate, amyl nitrite, sodium nitrite, 4-dimethylaminophenol, hydroxocobalamin, and dicobalt edetate ('Kelocyanor'), as well as several others[1]. Other commonly-recommended antidotes are 'solutions A and B' (a solution of ferrous sulphate in aqueous citric acid, and aqueous sodium carbonate) and amyl nitrite.

Britain's Health and Safety Executive has recommended against the use of solutions A and B because of their limited shelf life, potential to cause iron poisoning, and limited use (effective only in cases of cyanide ingestion, whereas the main modes of poisoning are ingestion and skin contact). The HSE has also questioned the usefulness of amyl nitrate due to storage/availability problems, risk of abuse, and lack of evidence of significant benefits, instead recommending Kelocyanor[2].

There is evidence from animal experiments that coadministration of glucose protects against cobalt toxicity associated with the antidote agent dicobalt edetate. For this reason, glucose is often administered alongside this agent (e.g. in the formulation 'Kelocyanor').

It has also been anecdotally suggested that glucose is itself an effective counteragent to cyanide, reacting with it to form less toxic compounds that can be eliminated by the body. One theory on the apparent immunity of Grigory Rasputin to cyanide was that his killers put the poison in sweet pastries and madeira wine, both of which are rich in sugar; thus, Rasputin would have been administered the poison together with massive quantities of antidote. One study found a reduction in cyanide toxicity in mice when the cyanide was first mixed with glucose[3]. However, as yet glucose on its own is not an officially acknowledged antidote to cyanide poisoning.

Adapted from the Wikipedia article "Toxicity", under the G.N U Free Docmentation License. Please also see http://en.wikipedia.org/wiki