Chemical Agents
BZ
BZ is among the classes of centrally-acting compounds, that act on the
central nervous system, which includes Fentanyl and Ketamine. Very small
doses of Fentanyl are effective in immobilizing limbs, but can cause depressed
respiration. Ketamine is generally used as a pediatric anesthetic and can be
dangerous when used on heart patients.
Physiological manifestations include induced dream-like state through
hallucinations, or even severe delirium, these effects being least severe on children and
the elderly. BZ is an effective stunning agent that acts by mydriasis (dilation of the
pupils), which can be extremely uncomfortable. BZ can also cause short-term memory loss,
and different people may experience different levels of side effects. The precise chemical formulation of BZ was kept secret. However the WHO
report speculates that it belongs to the family of psychochemical known as benzilates,
or Phenyl Glycolate Esters of 3-quinuclidinol. BZ produces profound mental
disturbances at a dose of 0.1 to 0.2 mg. The symptoms may appear half an hour after
exposure and may persist for some days. BZ has proven highly unpredictable in its effects and is not regarded
as a satisfactory chemical Agent, although it has been loaded into munitions and aerial
delivery systems.
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HD (Mustard Gas)
Mustard gas is a vesicant or blistering agent. Its code name is HD.
This agent was heavily employed in World War I and was stockpiled in World War II.
A large family of related mustard gases have been prepared, of which Bis
(2-chloro-ethyl) sulfide, is the basic example. This is a relatively nonvolatile,
water insoluble, oily liquid with a faintly agreeable odor. It has durability under normal
climatic conditions for several days.
A properly fitted mask will protect against GB and BZ; but in the cases
of HD and VX, all parts of the body must be covered.
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HC or S
HEXACHLORETHANE TITANIUM-TETRACHLORIDE
ANTHROQUINONE
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| Color code: |
Yellow |
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| Agent State: |
Microparticulate Solid |
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| Classification: |
Inert |
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Burning type grenades and projectiles are commonly used by law
enforcement officers in riots and civil disorders. They are used for several purposes,
primarily for determining the direction of the wind and have a definite psychological
effects on crowds.
Smoke grenades can be used in conjunction with either a CN or CS grenade;
and the smoke from them will mix with the smoke from the burning type grenade and carry
the chemicals to the desired area.
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GA (Tabun)
Ethyl phosphorodimethylamido-cyanidate
GA is a volatile, liquid anticholinesterase nerve agents that reacts
irreversibly with the enzyme cholinesterase, thereby permitting a deleterious
accumulation of acetylcholine at nerve endings, which can lead to rapid death.
Tabun (GA) is a neurotoxic agent with an i.v. LD50 in
monkeys of 50 mg/kg and in rabbits of 63 mg/kg17.
GA causes runny nose, tightness of chest, dimness of vision and
pinpointing of the eye pupils, difficulty in breathing, drooling and excessive sweating,
nausea, vomiting, cramps, involuntary defecation and urination, twitching, jerking and
staggering, headache, drowsiness, coma and convulsions, followed by cessation of breathing
and death.
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VX
The phosphorylthiocholine class of compounds was discovered independently by Ranaji
Goshem of ICI and by Lars-Erik Tammelin of the Swedish Institute of Defense Research in
1952. Shortly thereafter, the U.S. Army began a systematic investigation of this class of
compounds at Edgewood Arsenal; as a result, VX was developed and stockpiled by the United
States. A closely related compound referred to as V gas was manufactured and stockpiled by
the Soviet Union.
VX is a colorless liquid that is both less volatile and less soluble in
water than GB. It is also distinguished from GB by its increased potency and stability in
the environment. It will persist for several days to several weeks at normal temperatures.
VX has the chemical name methylphosphonothioic acid,
S-[2-[bis(1-methylethyl)amino]ethyl] O-ethyl ester, and has the molecular formula
C11H26NO2PS and formula weight 267.37.
The lethal concentration-exposure time is 10 mg-min/m3 . VX
will penetrate the skin; the lethal dose by the percutaneous route is about 6 mg-min/m3 15.
VX, or a closely related substance, was responsible for the death of
6,000 sheep at Dugway Proving Ground, Utah, in March, 1968.
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GB (Sarin)
Isopropyl methylphosphono-fluoridate
The first of the United States' seven standardized chemicals was agent
(GB) Isopropyl Methylphosphonofluoridate, the trivial name of which is Sarin.
This nerve gas was first made in a 1,000 pound batch, in Germany during
World War II. The German expertise in this line of chemicals developed from their earlier
research on insecticides.
GB is colorless, odorless, fairly volatile liquid that is very soluble
in water. It is intended to enter the body by inhalation, and the lethal airborne exposure
is about 100 mg-min/m3 . GB is not very persistent; splashed on the ground it
will quickly evaporate except in a very cold climate, where it may remain for up to two
days.
GB is one of a family of volatile, liquid, anticholinesterase nerve
agents that reacts irreversibly with the enzyme cholinesterase, thereby permitting
a deleterious accumulation of acetylcholine at nerve endings, which can lead to
rapid death.
Sarin is a nerve agent and causes running nose, maximal miosis, eye
pain, twitching eyelids, difficulty in accommodation, chest tightness, salivation,
coughing and sneezing, nausea, heartburn, fatigue, muscle fasciculation, insomnia,
diarrhea, frequent urination, dyspnea, ataxia, slow reaction, convulsions and, ultimately
coma, respiratory paralysis and death.
LD50 are as follow: man, 14 mg/kg, i.v.; monkey, 20 mg/kg,
i.v.
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Mustard Agents
Mustard agents are usually classified as "blistering
agents" owing to the similarity of the wounds caused by these substances resembling
burns and blisters. However, since mustard agents also cause severe damage to the eyes,
respiratory system and internal organs, they should preferably be described as
"blistering and tissue-injuring agents". Normal mustard agent,
bis-(2-chloroethyl)sulphide, reacts with a large number of biological molecules. The
effect of mustard agent is delayed and the first symptoms do not occur until between 2-24
hours after exposure.
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.
Incidents are still occurring annually in the neighborhood of Sweden
where people risk injury from mustard agent. This largely involves fishermen who are
exposed to mustard agent brought to the surface by fishing nets. The background is found
in the dumping of chemical weapons after the Second World War in waters off the Danish and
Swedish coasts. Many fishing ports in south Sweden and Denmark have resources to care for
injured people and to decontaminate equipment contaminated by mustard agent. Certain
resources are also available on the fishing vessels.
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.
Apart from mustard agent, there are also several other closely
related compounds which have been used as chemical weapons. During the 1930's, several
reports were published on the synthesis of nitrogen mustard agent and its remarkable
blistering effect. The mechanism of action and symptoms largely agree with those described
for mustard agent. Germans and Americans started the military production of nitrogen
mustard agent in 1941 and 1943, respectively, whereas the development in England was
abandoned following an explosion. There is no verified use of nitrogen mustard agents as
chemical weapons and their usefulness is restricted by these types of agents being
unsuitable for storage.
Physical and Chemical Properties
In 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.
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 14.4C. In
order to be able to effectively use mustard agent at lower temperatures, it has been mixed
with lewisite in some types of ammunition in a ratio of 2:3. This mixture has a
freezing-point of -26C. During the Second World War, a form of mustard agent with high
viscosity was manufactured by means of the addition of a polymer. This is the first known
example of a thickened CW agent.
Mustard agent can easily be dissolved in most organic solvents but
has negligible solubility in water. In aqueous solutions, mustard agent decomposes into
non-poisonous products by means of hydrolysis. This reaction is catalyzed by alkali.
However, only dissolved mustard agent reacts, which means that the decomposition proceeds
very slowly. Bleaching-powder and chloramines, however, react violently with mustard
agent, whereupon non-poisonous oxidation products are formed. Consequently, these
substances are used for the decontamination of mustard agent.
Mechanism of Action
The toxic effects of mustard agent depend on its ability to
covalently bind to other substances. The chlorine atom is spiked off the ethyl group and
the mustard agent is transferred to a reactive sulphonium ion. This ion can bind to a
large number of different biological molecules. Most of all it binds to nucleophiles such
as nitrogen in the base components of nucleic acids and sulphur in SH-groups in proteins
and peptides. Since mustard agent contains two "reactive groups", it can also
form a bridge between or within molecules. Mustard agent can destroy a large number of
different substances in the cell by means of alkylation and thereby influence numerous
processes in living tissue.
Symptoms
In 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 diarrhea 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 edema 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 defense will complicate the already
large risk of infection in people with severe skin and lung injuries.
Antidotes and Methods of Treatment
There 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 Agent
It 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.
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GD (Soman)
Pinacolyl methylphosphono-fluoridate; 1,2,2-trimethyl propyl
methyl-phosphonofluoridate
Soman is a family of volatile, liquid anticholinesterase nerve
agents. Soman reacts irreversibly with the enzyme cholinesterase (ChE), thereby
permitting a deleterious accumulation of acetylcholine at nerve endings, which can
lead to rapid death.
GD causes miosis, salivation, lachrymation, muscular twitching and
fasciculation, diarrhea, frequent urination, convulsions, coma, respiratory failure and
death.
These autonomic, central and somatic neuromuscular systems are
responsible for the lethal actions of GD.
LD50 values are: rhesus monkey, 7 mg/kg, s.c.; rabbit, 16
mg/kg19.
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Nerve Agents
Among lethal CW agents, the nerve agents have had an entirely
dominant role since the Second World War. Nerve agents acquired their name because they
affect the transmission of nerve impulses in the nervous system. All nerve agents belong
chemically to the group of organo-phosphorus compounds. They are stable and easily
dispersed, highly toxic and have rapid effects both when absorbed through the skin and via
respiration. Nerve agents can be manufactured by means of fairly simple chemical
techniques. The raw materials are inexpensive and generally readily available.
It was not until the early 1930's that German chemists observed that
organo-phosphorus compounds could be poisonous. In 1934, Dr. Gerhard Schrader, a chemist
at IG Farben, was given the task of developing a pesticide. Two years later a phosphorus
compound with extremely high toxicity was produced for the first time. According to
contemporary regulations, discoveries with military implications had to be reported to the
military authorities, which was also done with Schrader's discovery. This phosphorus
compound, given the name tabun, was the first of the substances later referred to as nerve
agents.
A factory for production of the new CW agent was built and a total
of 12 000 tones of tabun were produced during the years 1942-1945. At the end of the war
the Allies seized large quantities of this nerve agent. Up to the end of the war, Schrader
and his co-workers synthesized about 2 000 new organo-phosphorus compounds, including
sarin (1938). The third of the "classic" nerve agents, soman, was first produced
in 1944. These three nerve agents are known as G agents in the American nomenclature. The
manufacture of sarin never started properly and up to 1945 only about 0.5 tone of this
nerve agent was produced in a pilot plant.
Immediately after the war, research was mainly concentrated on
studies of the mechanisms of the nerve agents in order to discover more effective forms of
protection against these new CW agents. The results of these efforts led, however, not
only to better forms of` protection but also to new types of agents closely related to the
earlier ones.
By the mid-1950's a group of more stable nerve agents had been
developed, known as the V-agents in the American nomenclature. They are approximately
ten-fold more poisonous than sarin and are thus among the most toxic substances ever
synthesized.
The first publication of these substances appeared in 1955. The
authors, R. Ghosh and J.F. Newman, described one of the substances, known as Amiton, as
being particularly effective against mites. At this time, intensive research was being
devoted to the organo-phosphorus insecticides both in Europe and in the United States. At
least three chemical firms appear to have independently discovered the remarkable toxicity
of these phosphorus compounds during the years 1952-53. Surprisingly enough, some of these
substances were available on the market as pesticides. Nonetheless, they were soon
withdrawn owing to their considerable toxicity also to mammals.
In the United States, the choice fell in 1958 on a substance known
by its code name VX as suitable as a CW agent of persistent type. Full-scale production of
VX started in April 1961 but its structure was not published until 1972.
Physical and Chemical Properties
The most important nerve agents included in modern CW arsenals
are:
Tabun, O-ethyl dimethylamidophosphorylcyanide, with the American
denomination GA. This nerve agent is the easiest to manufacture. Consequently, it is more
likely that developing countries start their CW arsenal with this nerve agent whereas
industrialized countries consider tabun to be out-of-date and of limited use.
Sarin, isopropyl methylphosphonofluoridate, with the American
denomination GB, a volatile substance mainly taken up through inhalation.
Soman, pinacolyl methylphosphonofluoridate, with the American
denomination GD, a moderately volatile substance which can be taken up by inhalation or
skin contact.
Cyclohexyl methylphosphonofluoridate, with the American denomination
GF, a substance with low volatility which is taken up through skin contact and inhalation
of the substance either as a gas or aerosol.
O-ethyl S-diisopropylaminomethyl methylphosphonothiolate, better
known under the American denomination VX, a persistent substance which can remain on
material, equipment and terrain for long periods. Uptake is mainly through the skin but
also through inhalation of the substance as a gas or aerosol.
The formulae for these nerve agents are:
Tabun, GA: (CH3)2N-P(=O)(-CN)(-OC2H5)
Sarin, GB: CH3-P(=O)(-F)(-OCH(CH33)2)
Soman, GD: CH3-P(=O)(-F)(-CH(CH3)C(CH3)3
GF: CH3-P(=O)(-F)(cyklo-C6H11)
VX: CH3-P(=O)(-SCH2CH2N[CH(CH3)2]2)(-OC2H5)
The same type of phosphorus compounds are used as, for example,
insecticides. In the structure of insecticides P(=O) has generally been replaced by P(=S)
and a less reactive group than (-F), (-CN) or (-SCH2CH2N[CH(CH3)2]2) is used.
All nerve agents in pure state are colorless liquids. Their
volatility varies widely. The consistency of VX may be likened to an involatile oil and is
therefore classified as belonging to the group of persistent CW agents. Its effect is
mainly through direct contact with the skin. Sarin is at the opposite extreme, being an
easily volatile liquid (comparable with, e.g., water), and mainly taken up through the
respiratory organs. The volatility of soman, tabun and GF are between those of sarin and
VX.
By addition of a thickener it is possible for, e.g., soman, to be
transferred from the category of volatile CW agents to the persistent agents.
Sarin is very soluble in water whereas other nerve agents are more
sparingly soluble. VX has the unexpected property of being soluble in cold water but
sparingly soluble in warm water (>9.5C).
The most important chemical reactions of nerve agents take place
directly at the phosphorus atom. The P-X bond is easily broken by nucleophilic reagents,
such as water or hydroxyl ions (alkali). In aqueous solution at neutral pH the nerve
agents decompose slowly, whereas the reaction is greatly accelerated following the
addition of alkali. The result is a non-toxic phosphoric acid.
The pH-dependence on the rate of hydrolysis for sarin and VX at 25C
expressed as half-life (hours). The curves have been calculated from laboratory
experiments where pH was kept constant. On moist ground or snow, hydrolysis may be faster
than shown in the figure as a result of auto-catalysis. The acidic hydrolysis products
formed namely lead to a gradually lower pH and thus faster degradation.
The formation of the non-toxic phosphoric acid is also accelerated
by rise in temperature or by a catalyst (e.g., hypochlorite ions from bleaching powder).
This hydrolysis forms the basis of most decontamination procedures utilizing
decomposition. In general, we may assume that an area exposed to G-agents decontaminates
itself within a few days. However, V-agents may remain on the ground for several weeks
because of their greater stability with respect to water and their much lower volatility.
At pH-levels between 7 and 10 large quantities of VX are transformed into an extremely
non-volatile product of hydrolysis which is incapable of penetrating skin. Admittedly,
this is less toxic than VX but still implies a risk during decontamination.
The nucleophilic attack on the phosphorous atom (P) also forms the
basis of different types of color reaction used in detecting nerve agents.
Binary Technology
Most chemical ammunition can be described as unitary, which
implies that it contains one active ready-to-use CW agent. Binary technology implies that
the final stage in the synthesis of the nerve agent is moved from the factory into the
warhead, which thus functions as a chemical reactor. Two initial substances which are
stored in separate containers are mixed and allowed to react and form the nerve agent when
the ammunition (bomb, projectile, grenade, etc.) is on its way towards the target.
Until the actual moment of use, the ammunition contains only
relatively non-toxic initial substances. It is therefore considered to be safer to
manufacture, store, transport and, finally, destroy. However, some critics question
whether this practically untested type of new ammunition is reliable. The technique for
mixing substances in bombs and rockets is complicated and requires space. The reaction has
to be controlled (e.g., the temperature) and the process should preferably take place
without solvents.
The principle for the use of binary weapons. Two canisters with the
two liquid components are placed one after the other in the shell. When the shell is
fired, forces of inertia will press the liquid contents in the front canister backwards
and burst the wall separating the canisters. The rifling in the barrel gives the shell a
spinning velocity of about 15,000 r.p.m. which contributes to the mixing.
In 1991 Iraq declared to the United Nations Special Commission
(UNSCOM) a different binary munitions concept. According to this the munitions were stored
containing one component. Shortly before use the munitions were opened and the second
component was added. Thus the reaction began even before the munitions were launched.
Binary components for the three most common nerve agents (American
code names are given in brackets) are the following:
Sarin (GB-2): methylphosphoryldifluoride (DF) + isopropanol. The
isopropanol is included in a mixture (OPA) with isopropylamine which binds the hydrogen
fluoride generated.
Soman (GD-2): methylphosphoryldifluorid (DF) + pinacolylalcohol.
VX-2: O-ethyl O-2-diisopropylaminoethyl methylphosphonite (QL) +
sulphur.
Mechanism of Action
A characteristic of nerve agents is that they are extremely
toxic and that they have very rapid effect. The nerve agent, either as a gas, aerosol or
liquid, enters the body through inhalation or through the skin. Poisoning may also occur
through consumption of liquids or foods contaminated with nerve agents.
The route for entering the body is of importance for the period
required for the nerve agent to start having effect. It also influences the symptoms
developed and, to some extent, the sequence of the different symptoms. Generally, the
poisoning works faster when the agent is absorbed through the respiratory system than via
other routes. This is because the lungs contain numerous blood vessels and the inhaled
nerve agent can therefore rapidly diffuse into the blood circulation and thus reach the
target organs. Among these organs, the respiratory system is one of the most important. If
a person is exposed to a high concentration of nerve agent, e.g., 200 mg sarin/m3 (see
table) death may occur within a couple of minutes.
Poisoning takes longer when the nerve agent enters the body through
the skin. Nerve agents are more or less fat-soluble and can penetrate the outer layers of
the skin. However, it takes some time before the poison reaches the deeper blood vessels.
Consequently, the first symptoms do not occur until 20-30 minutes after the initial
exposure but subsequently the poisoning process may be rapid if the total dose of nerve
agent is high. The toxic effect of nerve agents depends on them becoming bound to an
enzyme, acetylcholinesterase, and thereby inhibit this vital enzyme's normal biological
activity in the cholinergic nervous system.
Symptoms
When exposed to a low dose of nerve agent, causing minor
poisoning, characteristic symptoms are increased production of saliva, a running nose and
a feeling of pressure on the chest. The pupil of the eye becomes contracted (miosis) which
impairs night-vision. The accommodation capacity of the eye is also reduced so that
short-range vision deteriorates and the victim feels pain when he tries to focus on an
object nearby. This is accompanied by headache. More unspecific symptoms are tiredness,
slurred speech, hallucinations and nausea.
Exposure to a higher dose leads to a more dramatic development and
symptoms are more pronounced. Bronchoconstriction and secretion of mucous in the
respiratory system leads to difficulty in breathing and to coughing. Discomfort in the
gastrointestinal tract may develop into cramp and vomiting. Involuntary discharge of urine
and defecation may also form part of the picture. The discharge of saliva is powerful and
the victim may experience running eyes and sweating. Symptoms from the skeletal muscles
are very typical. If the poisoning is moderate, this may express itself as muscular
weakness, local tremors or convulsions.
When exposed to a high dose of nerve agent, the muscular symptoms
are more pronounced. The victim may suffer convulsions and lose consciousness. To some
extent, the poisoning process may be so rapid that earlier mentioned symptoms may never
have time to develop.
Muscular paralysis caused by nerve agents also affects the
respiratory muscles. Nerve agents also affect the respiratory center of the central
nervous system. The combination of these two effects is the direct cause of death.
Consequently, death caused by nerve agents is a kind of death by suffocation.
The toxic effect depends on both the concentration of nerve agent in
the air inhaled (C) and the time of exposure (t). In extremely high concentrations there
is a simple relationship, C t, which gives a certain toxic effect. Inhalation of sarin
vapor with a concentration of 100 mg/m3 for one minute gives the same result as inhalation
of 50 mg/m3 for two minutes. However, at low concentrations this relationship does not
apply since the human body is capable of some degree of detoxification. In order to obtain
a corresponding effect, it is then necessary to have relatively longer periods of
exposure. The values given in the table for toxicity of nerve agents apply to high
concentrations.
Antidotes and Methods of Treatment
Nerve agents have an extremely rapid effect. If medical methods
of treatment are to serve any purpose, they must be introduced immediately. In many
countries, the armed forces have access to an auto-injector containing antidotes to nerve
agents. It is so simple to use that the soldier can easily give himself or another person
an intramuscular injection.
One example is the Swedish auto-injector, which contains two active
components: HI-6 (500 mg) and atropine (2 mg). HI-6 is an oxime which directly reacts with
the cause of the injury, i.e., nerve agent-inhibited acetylcholinesterase. HI-6 functions
as a reactivator which restores the enzyme to an operational condition. Oximes have a poor
penetration capacity into the brain and thus mainly work in the peripheral nervous system.
The various nerve agents cause poisoning which are more or less easy
to treat with oximes. From this standpoint, VX and sarin are the easiest to treat and all
oximes used increase the chances of surviving poisoning with these nerve agents. Obidoxime
is the most effective against tabun poisoning but also HI-6 has a positive effect. Soman
causes the most difficulty treated poisoning and can only be treated with HI-6.
Soman poisoning is complicated by the inhibited enzyme going through
an "ageing" process. Following the ageing the enzyme cannot be reactivated by
any oxime. It is possible that HI-6 has some further positive antidote effect in addition
to its reactivating ability.
The other active component in the auto-injector is atropine.
Atropine is the classical antidote in cases of poisoning by organo-phosphorus compounds.
It is a medication which relieves the symptoms but does not attack the cause of the
injury. Atropine becomes bound to the receptors for acetylcholine, which are present in
the cholinergic synapse (see figure). When acetylcholine is bound, the signal is
transmitted but if atropine has become bound to the receptor, then no such transmission
takes place. Atropine thus gives protection against the excess of acetylcholine which
results from inhibition of acetylcholinesterase. Atropine has effects only within certain
parts of the cholinergic nervous system.
There are two types of acetylcholine receptors, the nicotinic which
are found, e.g., in the skeletal muscles, and the muscarinic, which are found in, e.g.,
smooth muscles, glands and the central nervous system. Atropine blocks the muscarinic
receptors. Atropine and oxime may therefore be considered to complement each other and the
two antidotes also have a synergetic effect, i.e., they boost each other.
An additional auto-injector can be given to victims of nerve agents
if their situation does not improve within ten minutes. Subsequently, the victim should be
treated by qualified medical staff who should initially inject additional atropine and an
anti-convulsant drug, diazepam. In cases of severe poisoning by nerve agents, large doses
of atropine (grams) may be required. The level of operational acetylcholinesterase is
gradually restored by the body's own production but this process requires at least two
weeks. During this period, and possibly also later, the victim may require medical care
not only for mental disorders such as difficulty in sleeping, amnesia, difficulties in
concentrating, and anxiety, but also for muscular weakness. Mental problems may also occur
after long exposure to extremely low concentrations to nerve agents.
There are also medical antidotes which can be taken preventively.
These antidotes are taken as tablets and used when ordered in connection with maximum
C-preparedness. One of the tablets contains a carbamate, pyridostigmine, as active
ingredient. Pyridostigmine inhibits acetylcholinesterase and protects the enzyme against
inhibitory effects of nerve agents. The dose is low and leads to about 25 per cent
inhibition. The pyridostigmine-inhibited enzyme is continuously released to active state
and thereby can reasonably effectively maintain the transfer of nerve impulses despite
injury caused by nerve agents. The effect is restricted to the peripheral cholinergic
nervous system since the substance does not enter the brain.
Pyridostigmine does not cause any side effects since there is a
large excess of enzyme in the cholinergic synapse. In actual fact, 1-2 per cent of
functional enzyme is sufficient to have a functioning synapse. This explains why carbamate
pretreatment has such good effect.
Pretreatment with carbamate should be combined with oxime therapy
(the auto-injector) after the poisoning in order to provide maximum effect. This
combination reduces the toxic effects of all nerve agents.
A diazepam tablet is also generally given as a pretreatment,
primarily affecting the central nervous system. Diazepam strengthens the effect of other
nerve agent antidotes. There will be better prospects of survival and less injury.
Diazepam also provides protection against permanent brain damage which may result from
heavy exposure to nerve agents.
Pretreatment has best effect if a warning system is available and
operative, since the tablets need about 30 min. to have effect after being swallowed. The
best protective effect is achieved after about two hours, which is followed by decreasing
efficacy. If the situation so requires, treatment can be repeated at eight-hourly
intervals for some days. The tablets should not be taken once nerve agent injury has
occurred. Admittedly, diazepam has a positive effect but pyridostigmine at that stage will
aggravate the injury.
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