Mustard AgentsAn overview of the sulfur and nitrogen mustard agentsMustard Agents
Mustard agent was produced for the first time in 1822 but its harmful effects were not discovered until 1860. Mustard agent was first used as a CW agent during the latter part of the First World War and caused lung and eye injuries to a very large number of soldiers. Many of them still suffered pain 30-40 years after they had been exposed, mainly as a result of injuries to the eyes and chronic respiratory disorders. Towards the end of the Second World War a large number of soldiers and sailors were injured during a German attack on the Italian port of Bari. A cargoship loaded with mustard agent ammunition was hit and large amounts of mustard agent became mixed with the water. The victims swam around in the contaminated water but it was not realized until too late that a large number of people had been injured 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 quantities of chemical agents. About 5,000 Iranian soldiers have been reported killed, 10-20 per cent by mustard agent. In addition, there were 40,000 to 50,000 injured. A typical result of warfare with mustard agent is that the medical system is loaded with numerous injured who require long and demanding care.
Mustard agent is very simple to manufacture and can therefore be a "first
choice" when a country decides to build up a capacity for chemical warfare.
Physical and Chemical PropertiesIn its pure state, mustard agent is colorless and almost odorless. The name was given to mustard agent as a result of an earlier production method which yielded an impure mustard-smelling product. Mustard agent is also claimed to have a characteristic smell similar to rotten onions. However, the 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 injury to the respiratory system in concentrations which are so low that the human sense of smell cannot distinguish them.Mechanism of ActionThe toxic effects of mustard agent depend on its ability to bind to other substances. The chlorine atom can bind to a large number of different biological molecules. Most of all it binds to nitrogen in nucleic acids and sulphur in proteins. Mustard agent can destroy a large number of different substances in the cell.SymptomsIn the form of gas or liquid, mustard agent attacks the skin, eyes, lungs and gastro-intestinal tract. Internal organs may also be injured, mainly blood-generating organs, as a result of mustard agent being taken up through the skin or lungs and transported into the body. The delayed effect is a characteristic of mustard agent. Mustard agent gives no immediate 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 extend 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 which 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. The 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. Minor skin damage may be caused by mustard agent in the gaseous state whereas the most severe injuries are caused after contact with liquid mustard agent. Skin damage first appears as a painful inflammation. Depending on the level of exposure, the injury may develop into pigmentation, which flakes-off after a couple of weeks, small 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. Experience has shown that even extremely extensive skin damage, 80-90 %, can be cured if the patient is kept free of infection. However, injuries to the skin require a very long period of recuperation, much longer than thermal burns, and may require care and plastic surgery over a period of several months. Injury to the eyes appear initially as irritation with eye inflammation and a strong flow of tears. Depending on exposure, the symptoms thereafter may successively develop to sensitivity to light, swollen eyelids, and injury to the cornea. Severe damage to the eye may lead to the total loss of vision. Victims suffering damage to the eyes may encounter problems persisting up to 30-40 years following exposure. The most common cause of death as a result of mustard agent poisoning is complications after lung injury caused by inhalation of mustard agent. Lung injuries become apparent some hours 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 injuries. The effect on inner organs which is most pronounced 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 Methods of TreatmentThere is no treatment or antidote which 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. This decontamination will also decrease the risk of exposure to staff. Clothes are removed, the skin is decontaminated with a suitable decontaminant and washed with soap and water. If hair is suspected to be contaminated then it must be shaved off. Eyes are rinsed with water or a physiological salt solution for at least five minutes.In medical treatment, efforts are made to control infections by means of antibiotics. Pain can be eased by local anesthetics. After skin injuries have healed, it may be necessary 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 required. 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 AgentIt is impossible to identify a single mechanism for the damage caused by mustard agent. However, two possible important mechanisms can be mentioned where the first step in both is the formation of a reactive sulphonium ion. One such mechanism is the bonding of mustard agent to the base compounds in DNA (alkylation). The bonding may induce breakages of strands and the formation of bridges between the two strands in the DNA molecule. Bridges of this kind prevent DNA from functioning normally during cell division which 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.The 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 too large an amount of glutathion is bound by mustard agent, 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 disturbed.
Physical Properties of Mustard Agent
Toxicity of Mustard AgentInhalation: LCt50 1 500 mg*min/m3Skin exposure: LCt50 10 000 mg*min/m3 Smallest blister-causing dose on skin: 0,02 mg
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