Cyanide poisoning

Cyanide poisoning occurs when a living organism ingests cyanide. The cyanide ion, if used as poison, is generally delivered in the form of gaseous hydrogen cyanide or in the form of potassium cyanide or sodium cyanide.

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Toxicity of cyanides

Many cyanide-containing compounds are highly toxic, but many are not. The most dangerous cyanides are hydrogen cyanide (HCN) and salts derived from it, such as potassium cyanide (KCN) and sodium cyanide (NaCN), among others. The oral median lethal dose, or LD₅₀ of potassium cyanide is about 5–10 milligrams per kilogram of body weight for rats, mice, and rabbits.^[1]

Some compounds readily release HCN or the cyanide ion; for example such as trimethylsilyl cyanide (CH₃)₃SiCN upon contact with water and cyanoacrylates upon pyrolysis.^{[citation needed]} On the other hand, Prussian blue, with an approximate formula Fe₇(CN)₁₈ is the blue of blue prints and does not release cyanide ions easily. In fact, it is administered orally as an antidote to poisoning by thallium and Caesium-137.

Many thousands of organic compounds contain the CN group. These compounds are usually called nitriles although they are sometimes called organic cyanides. Generally, nitriles do not display high toxicity. In fact, the nitrile functional group is an integral component of numerous pharmaceutical drugs including cimetidine (Tagamet), verapamil (Isoptin), and citalopram (celexa). The reason for their diminished toxicity is that nitriles do not release the CN⁻ ion, which permanently binds to and inhibits cytochrome c oxidase, the specific basis of the lethality of cyanide (see below). Nitriles can be released from the burning of some plastics and may be a source of cyanide toxicity.

Absorption

The usual route of absorption is by inhalation of hydrogen cyanide gas, which forms when cyanide salts are treated with 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). Aqueous solutions of cyanides are not easily absorbed through the skin but solutions in DMSO are readily absorbed through the skin.

Mechanism of toxicity

Cyanide is an irreversible inhibitor of the enzyme cytochrome c oxidase (also known as aa₃) in the fourth complex in the membrane of the mitochondria of cells. It attaches to the iron within this protein. 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, meaning that the cell can no longer aerobically produce ATP for energy (95% of the energy produced by the human body comes from aerobic respiration). Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.

Plants contain an alternative pathway for respiration in their mitochondria. The alternate oxidase is not as efficient as the normal pathway, but it is immune to cyanide. Consequently, plants are insensitive to concentrations of cyanide that are lethal to animals, and a few species (e.g. the Giant Bamboo in its shoots) are known to contain cyanides.^[2] Interestingly, the Golden Bamboo Lemur is able to consume Giant Bamboo shoots containing many times the lethal dose of cyanide for humans and most other animals, with no ill effects. The reason for its immunity is not yet understood.^[2] Cyanide is rapidly metabolized in the human body. Different species exhibit widely differing sensitivities to cyanide. It is possible that there is also a considerable range of sensitivity among human individuals. The Regulatory information section below may give some guidance.

Acute poisoning

Inhalation of high concentrations of cyanide causes a coma with seizures, apnea and cardiac arrest, with death following in a matter of minutes. At lower doses, loss of consciousness may be preceded by general weakness, giddiness, headaches, vertigo, confusion, 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. Skin colour goes pink from high blood oxygen saturation.

Chronic exposure

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, which can result in weakness and a variety of symptoms, including permanent paralysis.

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, followed by intravenous sodium thiosulfate.^{[citation needed]} The nitrites oxidize some of the hemoglobin's iron from the ferrous state to the ferric state, converting the hemoglobin into methemoglobin. (Treatment with nitrites is not innocuous as methemoglobin cannot carry oxygen). Cyanide preferentially bonds to methemoglobin rather than the cytochrome oxidase, converting methemoglobin into cyanmethemoglobin. In the last step, the intravenous sodium thiosulfate converts the cyanmethemoglobin to thiocyanate, sulfite, and hemoglobin. The thiocyanate is excreted.

Alternative methods of treating cyanide intoxication are used in other countries. For example, in France hydroxycobalamin (a form of vitamin B₁₂) is used to bind 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 versatility 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 with (reportedly) lower toxicity. 4-DMAP is used currently by the German military and by the civilian population. In humans, intravenous injection of 3 mg/kg of 4-DMAP produces 35 percent methemoglobin levels within 1 minute. Reportedly, 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) that 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(HSE) has recommended against the use of solutions A and B because of their limited shelf life, potential to cause iron poisoning, and limited applicability (effective only in cases of cyanide ingestion, whereas the main modes of poisoning are inhalation and skin contact). The HSE has also questioned the usefulness of amyl nitrite due to storage/availability problems, risk of abuse, and lack of evidence of significant benefits, instead recommending Kelocyanor[2].

Evidence from animal experiments suggests 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.

Cyanide occurs in some foodstuffs, in small amounts. These are disposed of by enzymatic metabolism with rhodanase, combining cyanide with thiosulfate to produce comparatively harmless thiocyanate. Oral preparations of rhodanase are proposed as prophyllaxis and acute treatment for cyanide poisoining, currently under clinical trials in humans.^{[citation needed]}

Historical cases

Gas chambers

Hydrogen cyanide gas was the agent used during the Nazi regime in Germany for mass murder in some gas chambers during the Holocaust. It was released from Zyklon B pellets, a commercial biocide. It was also used in US execution chambers, where it was generated by reaction between potassium cyanide dropped into a compartment containing sulfuric acid directly below the chair in the chamber.

War

Cyanides were stockpiled in both the Soviet and the United States chemical weapons arsenals in the 1950s and 1960s.^{[citation needed]} During the Cold War, the Soviet Union was thought to be planning to use hydrogen cyanide as a "blitzkrieg" weapon to clear a path through the opposing front line, knowing that the hydrogen cyanide would dissipate and allow unprotected access to the captured zone.^{[citation needed]} However, as a military agent, hydrogen cyanide was not considered very effective, since it is lighter than air and needs a significant dose to incapacitate or kill.

Suicide

Cyanide salts are sometimes used as fast-acting suicide devices. Cyanide is reputed to work faster on an empty stomach, possibly because the anion is protonated by stomach acids to give HCN. Famous cyanide salt suicides include:

• Paul Lafargue and Laura Marx
• Erwin Rommel
• Eva Braun
• Leonard Lake
• Adolf Hitler bit his cyanide capsule at the same time as he shot himself.
• Wallace Carothers
• Hermann Göring
• Heinrich Himmler
• Alan Turing
• Odilo Globocnik
• A North-Korean agent identified as Kim Sung Il, who along with a female accomplice in police custody in Bahrain bit into cyanide tablets hidden in cigarettes after having left a bomb onboard Korean Air Flight 858 which subsequently exploded over the Indian Ocean on November 29, 1987. The woman's life was saved by a quick-thinking police officer who knocked the cigarette away at the last second.
• Ramón Sampedro
• Gavrilo Princip attempted suicide, but failed
• Nedeljko Čabrinović attempted suicide, but failed
• Behzad Nabavi attempted suicide, but failed

Members of the Liberation Tigers of Tamil Eelam which operate in north-eastern Sri Lanka are probably the most reported to use capsules made out of cyanide compound/compounds, where each member of the militia wears a capsule round their neck, which is used to commit suicide when they are about to be captured by the security forces of Sri Lanka.

Jonestown, Guyana was the site of a large mass suicide/murder, where 913 members of the Peoples Temple drank potassium cyanide-laced Flavor Aid in 1978.

Murder

See:

• Goebbels children
• Tylenol scare
• Ronald Clark O'Bryan
• Grigori Rasputin

In current events

Terrorists planned on releasing cyanide gas into the New York City Subway system shortly after the September 11th attacks. The attack was reportedly called off because there would not be enough casualties.^[3]

In fiction

Poisoning by cyanide figures prominently in crime fiction, for example Agatha Christie's Sparkling Cyanide (also entitled Remembered Death) and And Then There Were None. Cyanide is also the instrument of murder in The Big Sleep by Raymond Chandler and Roald Dahl's short story "The Landlady". In the Joseph Kesselring play "Arsenic and Old Lace," two old ladies mix wine with arsenic, cyanide and strychnine to use to kill old men. In the book "Hit Man: A Technical Manual for Independent Contractors", the use of cyanide to poison a mark is explained in detail.

Though not as famous as his Joker toxin or his electric joy-buzzers, the Joker from Batman comics is also known to use cyanide pies as one of his "comedic" weapons.

Australian author Nevil Shute's novel about life after nuclear war, On the Beach, gives the scenario of the Australian government giving survivors free cyanide tablets to commit suicide rather than face death from radiation poisoning.

In the James Bond movies and novels, 00 agents are issued cyanide capsules for use in the event of capture by the enemy. James Bond is described as having thrown his away. Assassins in the films have also used cyanide as a quick suicide method such as Mr. Jones in Dr. No, and in The Spy Who Loved Me, British and American nuclear submarines are threatened with the injection of Cyanide gas to force their crews to surrender to the villain's henchmen.

In the show 24 there are many instances where terrorists will bite a cyanide capsule to avoid harsh interrogation.

Satirical song writer Tom Lehrer managed to work this toxin into a line in his song "Poisoning Pigeons in the Park": When they see us coming / The birdies all try an' hide / But they still go for peanuts / When coated with cyan-hide.

Potassium cyanide is also the main ingredient in the fake death pill from the Metal Gear Solid 3: Snake Eater^[4]. It is an essential item to be used by Naked Snake in an emergency; it puts Naked Snake into a near-death state until he recovers himself using a revival pill. If he is left in the near-death state for too long then he will die.

In Phoenix Wright: Ace Attorney - Trials and Tribulations, the third case solved by the player involves a programmer who is murdered when potassium cyanide is slipped into his coffee at a restaurant.

Potassium cyanide was also featured in the novel and movie Battle Royale. Provided with a sample of the substance to use as a weapon, Yuko Sakaki, one of the female characters, employs the toxin to poison the spaghetti of another character. The tainted food reaches an unintended recipient in the form of Yuka Nakagawa, triggering the events in the infamous lighthouse scene.

See also

• Victims of poisoning

References

1. ^ Bernard Martel. Chemical Risk Analysis: A Practical Handbook. Kogan, 2004, page 361. ISBN 1903996651.
2. ^ ^{a b} D. A. Jones (1998). "Why are so many food plants cyanogenic?". Phytochemistry 47: 155-162. doi:10.1016/S0031-9422(97)00425-1.
3. ^ Time Magazine, The Untold Story of al-Qaeda's Plot to Attack the Subway, 19 Jun 2006, accessed 20 Jan 2007.
4. ^ Major Tom:"I'm afraid so. You've been given a 'fake death' pill for that purpose. SIS guidelines stipulate that soldiers on covert ops like this one, be issued a potassium cyanide capsule. Tape it to your body, so you can take it when you need to." (Metal Gear Solid 3: Snake Eater) Konami Computer Entertainment Japan, 2004