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This story was printed from Biological and Chemical Agents
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MUSTARD GAS

INTRODUCTION

Mustard agents are classified as "blistering agents" due to similarity of wounds caused by these substances similar to blisters & burns. Normal mustard agent, bis- (2-chloroethyl) sulphide, reacts with a many biological molecules.Effects of mustard agent are delayed and initial symptoms do not occur until between 2-24 hours after exposure. Mustard agent is easy to manufacture and can thus be a "first choice" when a nation decides to build up a capability for chemical warfare.

Mustard agent was first produced in 1822, but its detrimental effects were not discovered until 1860. Mustard agent was first used as CW agent during latter part of WW I and resulted in lung and eye injuries to numerous soldiers. Many of them still suffered pain 30-40 years after they had been exposed, mainly due to injuries to the eyes and chronic respiratory disorders.

Towards end of WWII many soldiers and sailors got injured during a German assault on Italian port of Bari. A cargoship loaded with mustard agent ammunition was hit and large quantities of mustard agent became mixed with the water. Victims swam around in contaminated water but it was not realized until too late that many people had been wounded by mustard agent. The Bari Incident served as a macabre illustration of the delayed effect of mustard agent.

During the war between Iran and Iraq in 1979-88, Iraq used large amounts of chemical agents. As many as 5000 Iranian soldiers were reported killed, 10-20% by mustard agent. In addition, there were 40 000 to 50 000 injured. A common effect of warfare with mustard agent is that the medical system is loaded with several injured, who require long and intensive care.

Incidents are still taking place annually in the neighbourhood of Sweden where people risk injury from mustard agent. This principally involves fishermen who are exposed to mustard agent brought to surface by fishing nets. The background is found in the dumping of chemical weapons after WWII in waters off Danish and Swedish coasts. Many fishing ports in south Sweden and Denmark have assets to care for wounded people and to decontaminate equipment polluted by mustard agent. Certain resources are also available on fishing vessels.

Apart from mustard agent, there are also numerous other closely related compounds that have been used as chemical weapons. During the 1930's, several reports were published on the synthesis of nitrogen mustard agent and its significant blistering effect. Mechanism of action and symptoms largely agree with those described for mustard agent. Germans and Americans started military production of nitrogen mustard agent in 1941 & 1943, respectively, whereas development in England was abandoned following an explosion. There is no established use of nitrogen mustard agents as chemical weapons and these types of agents being unsuitable for storage restrict their effectiveness.

PHYSICAL AND CHEMICAL PROPERTIES

In its pure state, mustard agent is colorless and odorless. The name was given to mustard agent due to an earlier production method that yielded impure mustard-smelling product. Mustard agent has a distinctive odor similar to rotten onions. However, sense of smell is dulled after only a few breaths so that the smell can no longer be distinguished. In addition, mustard agent can cause damage to the respiratory system in concentrations that are so low that the human sense of smell cannot perceive them.

At room temperature, mustard agent is a liquid with low volatility and is very stable during storage. The melting point for pure mustard agent is 14.4°C. In order to be able to effectively use mustard agent at lower temperatures; it has to be mixed with lewisite in some types of ammunition in a ratio of 2:3. Mixture has a freezing point of -26° C.

Mustard agent is easily dissolved in organic solvents but has negligible solubility in water. In aqueous solutions, mustard agent decomposes into non-poisonous products through the process of hydrolysis, that is catalyzed by an alkali. Nevertheless, only dissolved mustard agent reacts. Decomposition proceeds slowly. Bleaching powder and chloramines, but react violently with mustard agent, whereupon non-poisonous oxidation products are produced. Consequently, such chemicals are used for decontamination of mustard agent.

MECHANISM OF ACTION

Toxic effects of mustard agent depend on its ability to covalently bind to other compounds.Chlorine atom spikes off the ethyl group and mustard agent is shifted to a reactive sulphonium ion,that binds to various biological molecules. Primarily it binds to nucleophiles such as nitrogen in base components of nucleic acids and sulfur in SH-groups in proteins and peptides. Since mustard agent contains two "reactive groups", it can also form a bridge between molecules. Mustard agent can annihilate a large number of different material in the cell using alkylation and in so doing influence numerous processes in living tissue.

SYMPTOMS

In gaseous and liquid state, mustard agent attacks skin, eyes, lungs and gastro-intestinal tract. Internal organs can also be hurt, mainly blood-generating organs, as a result of mustard agent being absorbed through skin or lungs and transported into the body. Delayed effect is a characteristic of mustard agent. Mustard agent gives no instantaneous symptoms upon contact and consequently a delay of between two and twenty-four hours may occur before pain is felt and the victim becomes aware of what has happened. By then cell damage has already been caused.

Symptoms of mustard agent poisoning broaden over a wide range. Mild injuries consist of aching eyes with abundant flow of tears, inflammation of the skin, irritation of the mucous membrane, hoarseness, coughing and sneezing. Normally, these injuries do not require medical treatment. Severe injuries that are incapacitating and require medical care may involve eye injuries with loss of sight, the formation of blisters on the skin, nausea, vomiting and diarrhoea together with severe respiration difficulty.

Acute mortality arising from exposure to mustard agent is low. Dose needed to directly kill a person upon inhalation is, e.g., about 50 times larger than the dose giving acute mortality upon poisoning with the nerve agent Soman. People who die after exposure to mustard agent usually do so after a few days up to one or more weeks.

Mustard agent in the gaseous state may cause minor skin damage whereas the most severe injuries are caused after contact with liquid mustard agent. Skin damage first appears as a painful inflammation. Depending on level of exposure, injury may progress into pigmentation, which flakes-off after a few weeks, tiny surface blisters or deep liquid-filled blisters with subsequent skin necrosis. In extreme cases, the skin necrosis may be so comprehensive that no blisters occur. Skin injuries are more severe in humid and warm climates. Similarly, the injuries will be more severe where the skin is moist and warm, e.g., in the groin and armpits.

Most common cause of death due to mustard agent poisoning is complications after lung injury caused by inhalation of mustard agent. Lung injuries become evident some time after exposure and will first appear as a pressure across the chest, sneezing and hoarseness. Severe coughing and respiration difficulties caused by pulmonary oedema will gradually occur and after a couple of days, a "chemical pneumonia" may develop. Most of the chronic and late effects are also caused by lung damage.

The effect on inner organs which is most distinct is injury to the bone marrow, spleen and lymphatic tissue. This may cause a drastic reduction in the number of white blood cells 5-10 days after exposure, a condition very similar to that after exposure to radiation. This reduction of the immune defence will complicate the already large risk of infection in people with severe skin and lung injuries.

ANTIDOTES AND TREATMENT

There is no treatment or antidote that can affect the basic cause of mustard agent injury. Instead, efforts must be made to treat the symptoms. By far the most important measure is to rapidly and thoroughly decontaminate the patient and thereby prevent further exposure. 

Decontamination will also reduce risk of exposure to staff. Clothes are removed; skin is decontaminated with appropriate decontaminant and rinsed with soap and water. If hair is expected to be contaminated then it must be shaved off. Eyes are washed with water or a physiological salt solution for at least five to ten minutes.

In medical treatment, efforts are made to contain infections through antibiotics. Pain can be eased by local anaesthetics. After skin injuries have healed, it may be crucial to introduce plastic surgery. Lung injuries are treated with bronchodilatory treatment. Medicine to relieve coughing and also cortisone preparations may be used. Eye injuries are treated locally with painkillers and with antibiotics if necessary.

Despite treatment, inflammation and light sensitivity may remain for long periods.

Modern knowledge on the mechanisms behind mustard agent injuries may lead mainly to new ways of treatment. The first step, alkylation, takes place extremely rapidly and is probably very difficult to influence. Future treatment may concentrate on suppressing and alleviating the development of symptoms and thereby improve the opportunities for good recovery.

TYPES OF INJURY CAUSED BY MUSTARD AGENT

It is impossible to recognize a single mechanism for damage caused by mustard agent. However, two possible important mechanisms can be proved where the first step in both is  formation of a reactive sulphonium ion. One such mechanism is bonding of mustard agent to the base compounds in DNA (alkylation). Bonding may stimulate breakage of strands and formation of bridges between the two strands in the DNA molecule. Bridges of this kind prevent DNA from functioning normally during cell division that may lead to severe injury and possibly cell mortality. Damage to the DNA may also lead to mutations and disturbance to the natural repair mechanisms of DNA. The influence on DNA can cause the increased frequency of cancer observed after exposure to mustard agent.

Other mechanism of action is interaction between mustard agent and intracellular glutathion. Glutathion is a small peptide molecule which, among other things, takes care of the free radicals formed during cell respiration. If mustard agent binds too large an amount of glutathion, then the regulation of these free radicals no longer functions. Since free radicals are extremely toxic, this may lead to a number of processes in the cell being severely disturbed.

Mustard agent can also bind to different proteins in the cell. However, it is not known how much this contributes to the injuries caused. The binding takes place at the functional groups, e.g., the sulphydryl or amino groups. If the binding is made to, for example, the active site of enzymes, then their activity is inhibited which could lead to metabolic disorders. If, on the other hand, membrane proteins are bound, the result can be a modified uptake of substances and the inner environment of the cell will become unstable.

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