The effects of cyanide, specifically on the organelles

A. Hi, Brad. I don't know if the cyanide ever gets that far. My understanding is that it preferentially binds to hemoglobin so that the blood can no longer convey oxygen and the animal dies virtually instantly.

Regards,

A. Taken from my paper Trans Inst Met Fin, 2003, 81(4)

Hope it helps. The full paper has a lot more

Toxicology of Cyanides
It is widely held in the technical community that cyanide attaches to haemoglobin in the blood to form cyanhaemoglobin which defeats the oxygen carrying function2. Such a mechanism would be similar to the known effect of carbon monoxide and would imply a similar degree of toxicity. However, the effects of cyanide are much more severe than carbon monoxide and death occurs before the blood oxygen capacity has been sufficiently impaired to cause asphyxiation.

Mechanism of cyanide toxicity. The following section summarises the current state of knowledge of the mechanism of cyanide within the body.

Inhaled hydrogen cyanide passes almost immediately into the bloodstream where it is distributed throughout the body in about 2 minutes . Ingested cyanide is absorbed into the bloodstream via the stomach and gut lining. However, the rate of absorption depends heavily upon the condition within the stomach at the time of ingestion. The presence of a large volume of food effectively dilutes the dose while the rate of release of cyanide ion depends on the prevailing acidity. Ballantyne and Mars20.

Having entered the blood, the subsequent route for inhaled, ingested or absorbed cyanide is common. Cyanide and oxygen are distributed by the blood to cells throughout the body and both migrate into the cell structure by transport along a concentration gradient. With the exception of red blood cells, practically all cells are eucaryotic i.e. contain a structure known as the nucleus and a smaller structure, the mitochondrion. The mitochondrion is of crucial importance to the function of the entire organism since it is the site where energy is generated by the oxidative conversion of adenosine diphosphate (ADP) to adenosine triphosphate (ATP) Alberts et al (n.d.)21 p662. The reaction is reversible and the return of ATP to ADP releases much of the energy which fuels the essential inter and intra cellular activity. This reaction may be considered to be the main driving force of life itself and its disruption will inevitably be critical. In order to enter the mitochondrion, oxygen must traverse the mitochondrial membrane. This is achieved via a group of at least eight enzymes the cytochrome b c1 complex. ibid. pp. 677 et seq. The cytochrome molecule contains a bimetallic centre consisting of one copper and one iron atom which bond to the oxygen and carry it across the cell membrane, ibid. p 679. Any cyanide present forms an extremely strong bond with the iron atom, prevents the oxygen transfer and hence the generation of energy by the ATP/ADP reaction. The greatest energy users are the cells of the muscle tissues and neural fibres. The organism thus suffers asphyxiation at the cellular level and death will rapidly follow unless the problem can be reversed. The high energy requirement of muscle (particularly cardiac muscle) and neural tissues explain the observed symptoms of cyanide poisoning, deep and irregular breathing as the body seeks to obtain more oxygen followed by suppression of breathing and cardiac function as it fails to do so.

The median lethal dose of cyanide (LD50) in man is stated by Lewis27 as 3 mg kg 1. However Wallace Hayes28 p. 10, expands at some length on the problems of using this as a critical measure of toxicity. Dose /response curves for toxic substances are not linear, particularly where the body has a defence mechanism or a threshold dose must be exceeded before a response is observed. LD50 is a statistically derived dose obtained from animal experiments. It is sensitive to, inter alia, species, sex, dose rate, pre-existing conditions and feeding regime prior to dosing. Some of the problems of equating animal experiments to human response are discussed later. The concept of LDlo, the lowest observed lethal dose, is also used, but suffers from anomalies introduced by particularly susceptible individuals.

A similar mechanism makes cyanide toxic to most plants and other aerobic organisms. Solomonson in "Cyanide in Biology", Venisland25 p. 14 comments that 'cyanide is a rather common metabolite which can be formed from a variety of precursors which are widely distributed in nature'. This is particularly so in parts of the world where cassava forms a major part of the diet. This and many other potential human and animal foodstuffs contain cyanidic glycosides which hydrolyse to cyanide in the gut. Cyanide is also present in automotive exhaust gasses and tobacco smoke and is considered to be a normal constituent of blood. Detoxification.

Although not mentioned by any of the safety literature seen, the body has a considerable endogenous capacity to detoxify cyanide. First discovered by Jaffe in 1877, it was shown by Lang (1933) to be dependent on the enzyme rhodinase which controls the reaction of cyanide with thiosulphate to form much less toxic thiocyanate. The endogenous supply of available sulfur is limited and injection of sodium thiosulphate ⇦this on eBay or Amazon [affil links] is an important part of the accepted treatment of cyanide poisoning. CN + S 2 O3 &#8594 SO3 + SCN &#8594 Excretion via urine.

Other less significant detoxification routes are also known such as excretion of hydrogen cyanide via the lungs and binding to cystine or hydroxocobalamin, Meredith et al 22 p. 7. These mechanisms have several practical effects:-

-- The body will tolerate low doses of cyanide.
-- Tolerance to ingestion may be increased if absorption is delayed by favourable stomach conditions.
-- Low concentrations of hydrogen cyanide may be tolerated for extensive periods where the same time/concentration product inhaled at higher concentration for less time could be dangerous.
-- Supportive treatment alone may gain sufficient time for a patient to recover.

A. It is difficult to add much to my first submission without a very long and involved answer.
But to try to stay simple.-
Cyanide is transported by both hemoglobin and plasma. I have no evidence that it binds tightly to hemoglobin or causes irreversible changes. The damage is caused when the cyanide reaches the michrocondrium inside cells and effectively shuts off the oxygen supply. Death occurs while there is still plenty of oxygen available in the blood.
Cyanide is a normal constituent in blood arising from diet; cassava, lima beans, maize, millet etc. but normal cooking keeps these within acceptable limits. It is also universally present in air from tobacco smoke, vehicle emissions, etc. The body has evolved a number of defense mechanisms such as the reaction with hydroxocobalamin (vitamin B). Provided the cyanide does not enter the body faster than these mechanisms can cope, it does no long term harm. But if this limit is exceeded, the effects are rapid and lethal.
The rate at which cyanide leaves the body is subject to a large number of variables but I would expect the rate to decrease exponentially down to the 'normal' background level and would effectively never reach zero.

A. Hi Naha. Lima beans, apple pips, and other foods have potassium cyanide in them but are perfectly safe to eat because the dose is low. Does that answer your question? If not, please post the actual situation and why you want to know, rather than continuing in the abstract. Thanks.

Regards,

Q. It's just a curiosity in my mind whereby I want to know the lethal dose of Potassium Cyanide. Few days back, I saw the Spanish Movie "The Sea Inside" .

They showed that the lethal dose of this is 200 mg. Is it true? What if someone takes 2 grams or 1 gram?

A. Hi. In 1982 in Chicago, a criminal put potassium cyanide into Tylenol capsules and seven people died from ingesting them. These capsules would have been 500 mg, if they were filled to the top with pure potassium cyanide, so that obviously is plenty. Wikipedia suggests as low as 1.5 mg per kg of body weight, which for a 70 kg person would be 105 mg.

Regards,

A. Just an addition to previous entry: Cyanide binds to heme on cytochrome C of Complex IV in the electron transfer chain. The strong bond of cyanide to iron stops the proton-motive forces that enable the final reduction of electron-bearing oxygen to water.

A. Hi Jack
That is a wide ranging list of questions that is difficult to adequately address on a site like this.
A significant part I have answered earlier in the thread.
https://www.academia.edu/10635761/Cyanides_in_Metal_Finishing_Risks_and_Alternatives
Has coverage of much of the ground but, more importantly, will give you a list of references that you can pursue.
You can find the current first aid advice from HSE at http://www.hse.gov.uk/pubns/misc076.htm
I might add on the question of history that cyanide was mentioned in ancient Egypt (the peril of the peach) and was part of the US civil war medical kit. Prussic acid was only dropped from the British pharmacopeia in the 1940s.