acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

acetylcholinesterase inhibitor Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level an ...

poison A poison is any chemical substance that is harmful or lethal to living organisms. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figurati ...

pupil The pupil is a hole located in the center of the iris of the eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company. It appears black becau ...

salivation Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DN ...

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is often used as a synony ...

urination Urination is the release of urine from the bladder through the urethra in Placentalia, placental mammals, or through the cloaca in other vertebrates. It is the urinary system's form of excretion. It is also known medically as micturition, v ...

defecation Defecation (or defaecation) follows digestion and is the necessary biological process by which organisms eliminate a solid, semisolid, or liquid metabolic waste, waste material known as feces (or faeces) from the digestive tract via the anus o ...

asphyxiation Asphyxia or asphyxiation is a condition of deficient supply of oxygen to the body which arises from abnormal breathing. Asphyxia causes generalized hypoxia, which affects all the tissues and organs, some more rapidly than others. There are ...

cardiac arrest Cardiac arrest (also known as sudden cardiac arrest CA is when the heart suddenly and unexpectedly stops beating. When the heart stops beating, blood cannot properly Circulatory system, circulate around the body and the blood flow to the ...

respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies gr ...

aerosol An aerosol is a suspension (chemistry), suspension of fine solid particles or liquid Drop (liquid), droplets in air or another gas. Aerosols can be generated from natural or Human impact on the environment, human causes. The term ''aerosol'' co ...

respiratory system The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies grea ...

respirator A respirator is a device designed to protect the wearer from inhaling hazardous atmospheres including lead, lead fumes, vapors, gases and particulate matter such as dusts and airborne pathogens such as viruses. There are two main categories o ...

Sarin Sarin (NATO designation GB nerve_agent#G-series.html" ;"title="hort for nerve agent#G-series">G-series, "B" is an extremely toxic organophosphorus compound.VX are odorless; Tabun has a slightly fruity odor and

Soman Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibit ...

has a slight

camphor Camphor () is a waxy, colorless solid with a strong aroma. It is classified as a terpenoid and a cyclic ketone. It is found in the wood of the camphor laurel (''Cinnamomum camphora''), a large evergreen tree found in East Asia; and in the kapu ...

odor.

Biological effects

Nerve agents attack the

nervous system In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...

. All such agents function the same way resulting in

cholinergic crisis A cholinergic crisis is an over-stimulation at a neuromuscular junction due to an excess of acetylcholine, as a result of the inactivity of the acetylcholinesterase enzyme, which normally breaks down acetylcholine. Signs and symptoms As a resul ...

: they inhibit the enzyme

acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...

, which is responsible for the breakdown of

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

(ACh) in the

synapse In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

s between nerves that control whether muscle tissues are to relax or contract. If the agent cannot be broken down, muscles are prevented from receiving 'relax' signals and they are effectively paralyzed. It is the compounding of this paralysis throughout the body that quickly leads to more severe complications, including the heart and the muscles used for breathing. Because of this, the first symptoms usually appear within 30 seconds of exposure and death can occur via

asphyxia Asphyxia or asphyxiation is a condition of deficient supply of oxygen to the body which arises from abnormal breathing. Asphyxia causes generalized hypoxia, which affects all the tissues and organs, some more rapidly than others. There are m ...

tion or

cardiac arrest Cardiac arrest (also known as sudden cardiac arrest CA is when the heart suddenly and unexpectedly stops beating. When the heart stops beating, blood cannot properly Circulatory system, circulate around the body and the blood flow to the ...

in a few minutes, depending upon the dose received and the agent used. Initial symptoms following exposure to nerve agents (like

Sarin Sarin (NATO designation GB nerve_agent#G-series.html" ;"title="hort for nerve agent#G-series">G-series, "B" is an extremely toxic organophosphorus compound.constriction of the pupils. Soon after, the victim will have difficulty breathing and will experience nausea and salivation. As the victim continues to lose control of bodily functions, involuntary

salivation Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DN ...

,

lacrimation Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all land mammals. Tears are made up of water, electrolytes, proteins, lipids, and mucins that form layers on the surface of eyes. The different types of ...

,

urination Urination is the release of urine from the bladder through the urethra in Placentalia, placental mammals, or through the cloaca in other vertebrates. It is the urinary system's form of excretion. It is also known medically as micturition, v ...

,

defecation Defecation (or defaecation) follows digestion and is the necessary biological process by which organisms eliminate a solid, semisolid, or liquid metabolic waste, waste material known as feces (or faeces) from the digestive tract via the anus o ...

,

gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...

pain and

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

will be experienced.

Blister A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled ...

s and burning of the eyes and/or lungs may also occur. This phase is followed by initially myoclonic jerks (muscle jerks) followed by

status epilepticus Status epilepticus (SE), or status seizure, is a medical condition with abnormally prolonged seizures. It can have long-term consequences, manifesting as a single seizure lasting more than a defined time (time point 1), or 2 or more seizures over ...

–type epileptic seizure. Death then comes via complete respiratory depression, most likely via the excessive peripheral activity at the

neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...

of the diaphragm. The effects of nerve agents are long lasting and increase with continued exposure. Survivors of nerve agent poisoning almost invariably develop chronic neurological damage and related

psychiatric Psychiatry is the medical specialty devoted to the diagnosis, treatment, and prevention of deleterious mental conditions. These include matters related to cognition, perceptions, mood, emotion, and behavior. Initial psychiatric assessment of ...

effects. Possible effects that can last at least up to two–three years after exposure include blurred vision,

tiredness Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated with medical conditions ...

, declined memory, hoarse voice,

palpitations Palpitations occur when a person becomes aware of their heartbeat. The heartbeat may feel hard, fast, or uneven in their chest. Symptoms include a very fast or irregular heartbeat. Palpitations are a sensory symptom. They are often described as ...

,

sleeplessness Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

, shoulder stiffness and

eye strain Eye strain, also medically termed as asthenopia (), is a common eye condition characterized by nonspecific symptom, non-specific symptoms such as fatigue, pain in or around the eyes, blurred vision, headache, and occasional diplopia, double vis ...

. In people exposed to nerve agents, serum and

erythrocyte Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood ce ...

acetylcholinesterase in the long-term are noticeably lower than normal and tend to be lower the worse the persisting symptoms are.

Mechanism of action

When a normally functioning

motor nerve A motor nerve, or efferent nerve, is a nerve that contains exclusively efferent nerve fibers and transmits motor signals from the central nervous system (CNS) to the effector organs (muscles and glands), as opposed to sensory nerves, which transf ...

is stimulated, it releases the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

, which transmits the impulse to a muscle or organ. Once the impulse is sent, the enzyme

acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...

immediately breaks down the acetylcholine in order to allow the muscle or organ to relax. Nerve agents disrupt the nervous system by inhibiting the function of the enzyme acetylcholinesterase by forming a

covalent bond A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...

with its

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate, the ''binding s ...

, where acetylcholine would normally be broken down (undergo

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

). Acetylcholine thus builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. This same action also occurs at the gland and organ levels, resulting in uncontrolled drooling, tearing of the eyes (lacrimation) and excess production of mucus from the nose (rhinorrhea). The reaction product of the most important nerve agents, including Soman, Sarin, Tabun and VX, with acetylcholinesterase were solved by the U.S. Army using

X-ray crystallography X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...

in the 1990s. The reaction products have been confirmed subsequently using different sources of acetylcholinesterase and the closely related target enzyme, butyrylcholinesterase. The X-ray structures clarify important aspects of the reaction mechanism (e.g., stereochemical inversion) at atomic resolution and provide a key tool for antidote development.

Treatment

Standard treatment for nerve agent

poisoning Poisoning is the harmful effect which occurs when Toxicity, toxic substances are introduced into the body. The term "poisoning" is a derivative of poison, a term describing any chemical substance that may harm or kill a living organism upon ...

is a combination of an

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...

to manage the symptoms, and an

oxime In organic chemistry, an oxime is an organic compound belonging to the imines, with the general Chemical formula, formula , where R is an organic Side chain, side-chain and R' may be hydrogen, forming an aldoxime, or another organic functional g ...

as an antidote. Anticholinergics treat the symptoms by reducing the effects of acetylcholine, while oximes displaces phosphate molecules from the

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate, the ''binding s ...

of the

cholinesterase The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters: : an acylcholine + H2O = choline + a carboxylate Several of these serve as neurotransmitte ...

enzymes, allowing the breakdown of acetylcholine. Military personnel are issued the combination in an

autoinjector An autoinjector (or auto-injector) is a medical device for injection of a premeasured dose of a particular drug. Most autoinjectors are one-use, disposable, spring-loaded syringes (prefilled syringes). By design, autoinjectors are easy to use an ...

(e.g. ATNAA), for ease of use in stressful conditions.

Atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically give ...

is the standard anticholinergic drug used to manage the symptoms of nerve agent poisoning. It acts as an antagonist to

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...

s, blocking the effects of excess acetylcholine. Some synthetic anticholinergics, such as

biperiden Biperiden, sold under the brand name Akineton among others, is a medication used to treat Parkinson disease, certain drug-induced movement disorders and Tourette Syndrome. It is not recommended for tardive dyskinesias. It is taken by mouth, in ...

, may counteract the central symptoms of nerve agent poisoning more effectively than atropine, since they pass the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

better. While these drugs will save the life of a person affected by nerve agents, that person may be incapacitated briefly or for an extended period, depending on the extent of exposure. The endpoint of atropine administration is the clearing of bronchial secretions. Pralidoxime chloride (also known as ''2-PAMCl'') is the standard oxime used to treat nerve agent poisoning. Rather than counteracting the initial effects of the nerve agent on the nervous system as does atropine, pralidoxime chloride reactivates the poisoned enzyme (acetylcholinesterase) by scavenging the phosphoryl group attached on the functional hydroxyl group of the enzyme, counteracting the nerve agent itself. Revival of acetylcholinesterase with pralidoxime chloride works more effectively on nicotinic receptors while blocking acetylcholine receptors with atropine is more effective on

muscarinic receptors Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-recep ...

.

Anticonvulsant Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...

s, such as diazepam, may be administered to manage seizures, improving long term prognosis and reducing risk of brain damage. This is not usually self-administered as its use is for actively seizing patients.

Countermeasures

Pyridostigmine bromide was used by the

US military The United States Armed Forces are the military forces of the United States. U.S. federal law names six armed forces: the Army, Marine Corps, Navy, Air Force, Space Force, and the Coast Guard. Since 1949, all of the armed forces, except th ...

in the first Gulf War as a pretreatment for

Soman Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibit ...

as it increased the

median lethal dose In toxicology, the median lethal dose, LD50 (abbreviation for " lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a given substance. The value of LD50 for a substance is the dose re ...

. It is only effective if taken prior to exposure and in conjunction with Atropine and Pralidoxime, issued in the Mark I NAAK autoinjector, and is ineffective against other nerve agents. While it reduces fatality rates, there is an increased risk of brain damage; this can be mitigated by administration of an anticonvulsant. Evidence suggests that the use of pyridostigmine may be responsible for some of the symptoms of Gulf War syndrome.

Butyrylcholinesterase Butyrylcholinesterase ( HGNC symbol BCHE; EC 3.1.1.8), also known as BChE, BuChE, BuChase, pseudocholinesterase, or plasma (cholin)esterase, is a nonspecific cholinesterase enzyme that hydrolyses many different choline-based esters. In humans, i ...

is under development by the U.S. Department of Defense as a

prophylactic Preventive healthcare, or prophylaxis, is the application of healthcare measures to prevent diseases.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental health a ...

countermeasure A countermeasure is a measure or action taken to counter or offset another one. As a general concept, it implies precision and is any technological or tactical solution or system designed to prevent an undesirable outcome in the process. The fi ...

against

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

nerve agents. It binds nerve agent in the bloodstream before the poison can exert effects in the nervous system. Both purified

acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...

and butyrylcholinesterase have demonstrated success in animal studies as "biological scavengers" (and universal targets) to provide

stoichiometric Stoichiometry () is the relationships between the masses of reactants and products before, during, and following chemical reactions. Stoichiometry is based on the law of conservation of mass; the total mass of reactants must equal the total m ...

protection against the entire spectrum of organophosphate nerve agents. Butyrylcholinesterase currently is the preferred enzyme for development as a pharmaceutical drug primarily because it is a naturally circulating human plasma protein (superior

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...

) and its larger active site compared with acetylcholinesterase may permit greater flexibility for future design and improvement of butyrylcholinesterase to act as a nerve agent scavenger.

Classes

There are two main classes of nerve agents. The members of the two classes share similar properties and are given both a common name (such as ''Sarin'') and a two-character

NATO The North Atlantic Treaty Organization (NATO ; , OTAN), also called the North Atlantic Alliance, is an intergovernmental organization, intergovernmental Transnationalism, transnational military alliance of 32 Member states of NATO, member s ...

identifier (such as GB).

G-series

The ''G-series'' is thus named because German scientists first synthesized them. G series agents are known as non-persistent, meaning that they evaporate shortly after release, and do not remain active in the dispersal area for very long. All of the compounds in this class were discovered and synthesized during or prior to

World War II World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...

, led by

Gerhard Schrader Gerhard Schrader (25 February 1903 – 10 April 1990) was a German chemist specializing in the discovery of new insecticides, hoping to make progress in the fight against hunger in the world. Schrader is best known for his accidental discovery of ...

(later under the employment of

IG Farben I. G. Farbenindustrie AG, commonly known as IG Farben, was a German Chemical industry, chemical and Pharmaceutical industry, pharmaceutical conglomerate (company), conglomerate. It was formed on December 2, 1925 from a merger of six chemical co ...

). This series is the first and oldest family of nerve agents. The first nerve agent ever synthesized was GA ( Tabun) in 1936. GB (

Sarin Sarin (NATO designation GB nerve_agent#G-series.html" ;"title="hort for nerve agent#G-series">G-series, "B" is an extremely toxic organophosphorus compound.Soman Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibit ...

) in 1944, and finally the more obscure GF ( Cyclosarin) in 1949. GB was the only G agent that was fielded by the US as a munition, in rockets, aerial bombs, and

artillery shell A shell, in a modern military context, is a projectile whose payload contains an explosive, incendiary device, incendiary, or other chemical filling. Originally it was called a bombshell, but "shell" has come to be unambiguous in a military ...

s.

V-series

The ''V-series'' is the second family of nerve agents and contains five well known members: VE, VG, VM, VR, and VX, along with several more obscure analogues. The most studied agent in this family, VX (it is thought that the "X" in its name comes from its overlapping isopropyl radicals), was invented in the 1950s at Porton Down in

Wiltshire Wiltshire (; abbreviated to Wilts) is a ceremonial county in South West England. It borders Gloucestershire to the north, Oxfordshire to the north-east, Berkshire to the east, Hampshire to the south-east, Dorset to the south, and Somerset to ...

, England. Ranajit Ghosh, a chemist at the Plant Protection Laboratories of

Imperial Chemical Industries Imperial Chemical Industries (ICI) was a British Chemical industry, chemical company. It was, for much of its history, the largest manufacturer in Britain. Its headquarters were at Millbank in London. ICI was listed on the London Stock Exchange ...

(ICI) was investigating a class of organophosphate compounds (organophosphate esters of substituted aminoethanethiols). Like Schrader, Ghosh found that they were quite effective pesticides. In 1953 and 1954, ICI conducted field trials, intending to market the material as an

acaricide Acaricides are pesticides that kill members of the arachnid subclass '' Acari'', which includes ticks and mites. Acaricides are used both in medicine and agriculture, although the desired selective toxicity differs between the two fields. Termi ...

with the common name amiton. Development was halted, as it was too toxic for safe use. The toxicity did not escape military notice and some of the more toxic materials had been sent to Porton Down for evaluation. After the evaluation was complete, several members of this class of compounds became a new group of nerve agents, the V agents (depending on the source, the V stands for Victory, Venomous, or Viscous). The best known of these is probably VX, with VR ("Russian V-gas") coming a close second (amiton is largely forgotten as VG, with G probably coming from "G"hosh). All of the V-agents are persistent agents, meaning that these agents do not degrade or wash away easily and can therefore remain on clothes and other surfaces for long periods. In use, this allows the V-agents to be used to blanket terrain to guide or curtail the movement of enemy ground forces. The consistency of these agents is similar to oil; as a result, the contact hazard for V-agents is primarily – but not exclusively – dermal. VX was the only V-series agent that was fielded by the US as a munition, in rockets,

artillery shell A shell, in a modern military context, is a projectile whose payload contains an explosive, incendiary device, incendiary, or other chemical filling. Originally it was called a bombshell, but "shell" has come to be unambiguous in a military ...

s, airplane spray tanks, and

landmine A land mine, or landmine, is an explosive weapon often concealed under or camouflaged on the ground, and designed to destroy or disable enemy targets as they pass over or near it. Land mines are divided into two types: anti-tank mines, whi ...

s.''FM 3–8 Chemical Reference handbook''; US Army; 1967 Analyzing the structure of thirteen V agents, the standard composition, which makes a compound enter this group, is the absence of

halides In chemistry, a halide (rarely halogenide) is a binary chemical compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative (or more electropositive) than the halogen, to make a fluo ...

. It is clear that many agricultural pesticides can be considered as V agents if they are notoriously toxic. The agent is not required to be a phosphonate and presents a dialkylaminoethyl group. The toxicity requirement is waived as the VT agent and its salts (VT-1 and VT-2) are "non-toxic". Replacing the sulfur atom with selenium increases the toxicity of the agent by orders of magnitude.

Novichok agents

The Novichok (Russian: , "newcomer") agents, a series of

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

compounds, were developed in the

Soviet Union The Union of Soviet Socialist Republics. (USSR), commonly known as the Soviet Union, was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 until Dissolution of the Soviet ...

and in Russia from the mid-1960s to the 1990s. The Novichok program aimed to develop and manufacture highly deadly chemical weapons that were unknown to the West. The new agents were designed to be undetectable by standard NATO chemical-detection equipment and overcome contemporary chemical-protective equipment. In addition to the newly developed "third generation" weapons, binary versions of several Soviet agents were developed and were designated as "Novichok" agents.

Carbamates

Contrary to some claims, not all nerve agents are

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

s. The starting compound studied by the United States was the

carbamate In organic chemistry, a carbamate is a category of organic compounds with the general Chemical formula, formula and Chemical structure, structure , which are formally Derivative (chemistry), derived from carbamic acid (). The term includes orga ...

EA-1464, of notorious toxicity.SUMMARY OF MAJOR EVENTS and PROBLEMS. United States Army Chemical Corps (U). FISCAL YEAR 1960. p-116 Compounds similar in structure and effect to EA-1464 formed a large group, including compounds such as EA-3990 and EA-4056. The Family Practice Notebook claims carbamate-based nerve agents can be three times as toxic as VX. Both the United States and the Soviet Union developed carbamate-based nerve agents during the

Cold War The Cold War was a period of global Geopolitics, geopolitical rivalry between the United States (US) and the Soviet Union (USSR) and their respective allies, the capitalist Western Bloc and communist Eastern Bloc, which lasted from 1947 unt ...

. Carbamate-based nerve agents are sometimes grouped in academic literature with Fourth Generation Novichok agents, as they were added to the CWC schedule on banned agents at the same time, despite their significant differences in chemical makeup and mechanisms of action. Carbamate-based nerve agents have been identified as Schedule 1 Nerve Agents, the highest classification possible under the CWC, reserved for agents with no identified alternate use, and those that can cause the most harm.

Insecticides

Some

insecticide Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. The major use of insecticides is in agriculture, but they are also used in home and garden settings, i ...

s, including

carbamates In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formally obt ...

and

organophosphates In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

such as

dichlorvos Dichlorvos (2,2-dichlorovinyl dimethyl phosphate, commonly abbreviated as an DDVP) is an organophosphate widely used as an insecticide to control household pests, in public health, and protecting stored products from insects. The compound has be ...

,

malathion Malathion is an organophosphate insecticide which acts as an acetylcholinesterase inhibitor. In the USSR, it was known as carbophos, in New Zealand and Australia as maldison and in South Africa as mercaptothion. The compound's name is presumably ...

and

parathion Parathion, also called parathion-ethyl or diethyl parathion, is an organophosphate insecticide and acaricide. It was originally developed by IG Farben in the 1940s. It is highly toxic to non-target organisms, including humans, so its use has been ...

, are nerve agents. The metabolism of

insect Insects (from Latin ') are Hexapoda, hexapod invertebrates of the class (biology), class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body (Insect morphology#Head, head, ...

s is sufficiently different from

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

s that these compounds have little effect on

humans Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

and other

mammals A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...

at proper doses, but there is considerable concern about the effects of long-term exposure to these chemicals by

farm workers A farmworker, farmhand or agricultural worker is someone employed for labor in agriculture. In labor law, the term "farmworker" is sometimes used more narrowly, applying only to a hired worker involved in agricultural production, including har ...

and

animals Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia (). With few exceptions, animals consume organic material, breathe oxygen, have myocytes and are able to move, can reproduce sexually, and grow from a ...

alike. At high enough doses, acute toxicity and death can occur through the same mechanism as other nerve agents. Some insecticides such as demeton, dimefox and

paraoxon Paraoxon is a parasympathomimetic drug which acts as an cholinesterase inhibitor. It is an organophosphate oxon, and the active metabolite of the insecticide parathion. It is also used as an ophthalmological drug against glaucoma. Paraoxon is o ...

are sufficiently toxic to humans that they have been withdrawn from agricultural use, and were at one stage investigated for potential military applications. Paraoxon was allegedly used as an

assassination Assassination is the willful killing, by a sudden, secret, or planned attack, of a personespecially if prominent or important. It may be prompted by political, ideological, religious, financial, or military motives. Assassinations are orde ...

weapon by the

apartheid Apartheid ( , especially South African English: , ; , ) was a system of institutionalised racial segregation that existed in South Africa and South West Africa (now Namibia) from 1948 to the early 1990s. It was characterised by an ...

South African government as part of

Project Coast Project Coast was a top-secret chemical and biological weapons (CBW) programme instituted by the apartheid-era government of South Africa in the 1980s. Project Coast was the successor to a limited postwar CBW programme, which mainly produced the ...

. Organophosphate

pesticide poisoning A pesticide poisoning occurs when pesticides, chemicals intended to control a pest, affect non-target organisms such as humans, wildlife, plants, or bees. There are three types of pesticide poisoning. The first of the three is a single and sho ...

is a major cause of disability in many developing countries and is often the preferred method of suicide.

Methods of dissemination

Many methods exist for spreading nerve agents such as: *uncontrolled

aerosol An aerosol is a suspension (chemistry), suspension of fine solid particles or liquid Drop (liquid), droplets in air or another gas. Aerosols can be generated from natural or Human impact on the environment, human causes. The term ''aerosol'' co ...

munitions *smoke generation *explosive dissemination * atomizers,

humidifier A humidifier is a household appliance or device designed to increase the moisture level in the air within a room or an enclosed space. It achieves this by emitting water droplets or steam into the surrounding air, thereby raising the humidity. ...

s and foggers The method chosen will depend on the physical properties of the nerve agent(s) used, the nature of the target, and the achievable level of sophistication.

History

Discovery

This first class of nerve agents, the G-series, was accidentally discovered in Germany on December 23, 1936, by a research team headed by

Gerhard Schrader Gerhard Schrader (25 February 1903 – 10 April 1990) was a German chemist specializing in the discovery of new insecticides, hoping to make progress in the fight against hunger in the world. Schrader is best known for his accidental discovery of ...

working for

IG Farben I. G. Farbenindustrie AG, commonly known as IG Farben, was a German Chemical industry, chemical and Pharmaceutical industry, pharmaceutical conglomerate (company), conglomerate. It was formed on December 2, 1925 from a merger of six chemical co ...

. Since 1934, Schrader had been working in a laboratory in

Leverkusen Leverkusen () is a city in North Rhine-Westphalia, Germany, on the eastern bank of the Rhine. To the south, Leverkusen borders the city of Cologne, and to the north the state capital, Düsseldorf. The city is part of the Rhine-Ruhr Metropolitan ...

to develop new types of

insecticide Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. The major use of insecticides is in agriculture, but they are also used in home and garden settings, i ...

s for

IG Farben I. G. Farbenindustrie AG, commonly known as IG Farben, was a German Chemical industry, chemical and Pharmaceutical industry, pharmaceutical conglomerate (company), conglomerate. It was formed on December 2, 1925 from a merger of six chemical co ...

. While working toward his goal of improved insecticide, Schrader experimented with numerous compounds, eventually leading to the preparation of Tabun. In experiments, Tabun was extremely potent against insects: as little as 5 ppm of Tabun killed all the leaf lice he used in his initial experiment. In January 1937, Schrader observed the effects of nerve agents on human beings first-hand when a drop of Tabun spilled onto a lab bench. Within minutes he and his laboratory assistant began to experience

miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

(constriction of the pupils of the eyes), dizziness and severe shortness of breath. It took them three weeks to recover fully. In 1935 the

Nazi Nazism (), formally named National Socialism (NS; , ), is the far-right politics, far-right Totalitarianism, totalitarian socio-political ideology and practices associated with Adolf Hitler and the Nazi Party (NSDAP) in Germany. During H ...

government had passed a decree that required all inventions of possible military significance to be reported to the Ministry of War, so in May 1937 Schrader sent a sample of Tabun to the chemical warfare (CW) section of the Army Weapons Office in Berlin-Spandau. Schrader was summoned to the Wehrmacht chemical lab in Berlin to give a demonstration, after which Schrader's

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an sufficiency of disclosure, enabling discl ...

application and all related research was classified as secret. Colonel Rüdiger, head of the CW section, ordered the construction of new laboratories for the further investigation of Tabun and other organophosphate compounds and Schrader soon moved to a new laboratory at

Wuppertal Wuppertal (; ) is a city in North Rhine-Westphalia, in western Germany, with a population of 355,000. Wuppertal is the seventh-largest city in North Rhine-Westphalia and List of cities in Germany by population, 17th-largest in Germany. It ...

-

Elberfeld Elberfeld is a municipal subdivision of the Germany, German city of Wuppertal; it was an independent town until 1929. History The first official mentioning of the geographic area on the banks of today's Wupper River as "''elverfelde''" was ...

in the Ruhr valley to continue his research in secret throughout

World War II World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...

. The compound was initially codenamed Le-100 and later Trilon-83.

Sarin Sarin (NATO designation GB nerve_agent#G-series.html" ;"title="hort for nerve agent#G-series">G-series, "B" is an extremely toxic organophosphorus compound.Gerhard Schrader, Otto Ambros, , and Hans-Jürgen von der Linde. It was codenamed T-144 or Trilon-46. It was found to be more than ten times as potent as Tabun.

Soman Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibit ...

was discovered by

Richard Kuhn Richard Johann Kuhn (; 3 December 1900 – 31 July 1967) was an Austrian-German biochemist who was awarded the Nobel Prize in Chemistry in 1938 "for his work on carotenoids and vitamins". Biography Early life Kuhn was born in Vienna, Austria ...

in 1944 as he worked with the existing compounds; the name is derived from either the

Greek Greek may refer to: Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group *Greek language, a branch of the Indo-European language family **Proto-Greek language, the assumed last common ancestor of all kno ...

'to sleep' or the

Latin Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...

'to bludgeon'. It was codenamed T-300. Cyclosarin was also discovered during WWII but the details were lost and it was rediscovered in 1949. The G-series naming system was created by the United States when it uncovered the German activities, labeling Tabun as GA (German Agent A), Sarin as GB and Soman as GD. Ethyl Sarin was tagged GE and Cyclosarin as GF.

During World War II

In 1939, a pilot

plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they are predominantly Photosynthesis, photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with c ...

for Tabun production was set up at Munster-Lager, on

Lüneburg Heath Lüneburg Heath (, ) is a large area of heath (habitat), heath, geest, and woodland in the northeastern part of the state of Lower Saxony in northern Germany. It forms part of the hinterland for the cities of Hamburg, Hanover and Bremen and is ...

near the German Army proving grounds at . In January 1940, construction began on a secret plant, code named " Hochwerk" (''High factory''), for the production of Tabun at ''Dyhernfurth an der Oder'' (now

Brzeg Dolny Brzeg Dolny () is a town in Wołów County, Lower Silesian Voivodeship in south-western Poland. It is located north-west of Wrocław on the Oder River, and is the site of a large chemical plant complex, PCC Rokita SA. As of December 2021, the ...

in

Poland Poland, officially the Republic of Poland, is a country in Central Europe. It extends from the Baltic Sea in the north to the Sudetes and Carpathian Mountains in the south, bordered by Lithuania and Russia to the northeast, Belarus and Ukrai ...

), on the

Oder River The Oder ( ; Czech and ) is a river in Central Europe. It is Poland's second-longest river and third-longest within its borders after the Vistula and its largest tributary the Warta. The Oder rises in the Czech Republic and flows through west ...

from Breslau (now

Wrocław Wrocław is a city in southwestern Poland, and the capital of the Lower Silesian Voivodeship. It is the largest city and historical capital of the region of Silesia. It lies on the banks of the Oder River in the Silesian Lowlands of Central Eu ...

) in

Silesia Silesia (see names #Etymology, below) is a historical region of Central Europe that lies mostly within Poland, with small parts in the Czech Silesia, Czech Republic and Germany. Its area is approximately , and the population is estimated at 8, ...

. The plant was large, covering an area of and was completely self-contained, synthesizing all intermediates as well as the final product, Tabun. The factory even had an underground plant for filling munitions, which were then stored at Krappitz (now

Krapkowice Krapkowice (; ; ) is a town in southern Poland with 16,301 inhabitants (2019), situated in the Opole Voivodeship, straddling both banks of the Oder River at the point where it joins with the Osobłoga. It is the regional capital of Krapkowice Cou ...

) in Upper Silesia. The plant was operated by , a subsidiary of

IG Farben I. G. Farbenindustrie AG, commonly known as IG Farben, was a German Chemical industry, chemical and Pharmaceutical industry, pharmaceutical conglomerate (company), conglomerate. It was formed on December 2, 1925 from a merger of six chemical co ...

, as were all other chemical weapon agent production plants in Germany at the time. Because of the plant's deep secrecy and the difficult nature of the production process, it took from January 1940 until June 1942 for the plant to become fully operational. Many of Tabun's chemical precursors were so corrosive that reaction chambers not lined with quartz or silver soon became useless. Tabun itself was so hazardous that the final processes had to be performed while enclosed in double glass-lined chambers with a stream of pressurized air circulating between the walls. Three thousand German nationals were employed at Hochwerk, all equipped with

respirators A respirator is a device designed to protect the wearer from inhaling hazardous atmospheres including lead, lead fumes, vapors, gases and particulate matter such as dusts and airborne pathogens such as viruses. There are two main categories o ...

and

clothing Clothing (also known as clothes, garments, dress, apparel, or attire) is any item worn on a human human body, body. Typically, clothing is made of fabrics or textiles, but over time it has included garments made from animal skin and other thin s ...

constructed of a poly-layered rubber/cloth/rubber sandwich that was destroyed after the tenth wearing. Despite all precautions, there were over 300 accidents before production even began and at least ten workers died during the two and a half years of operation. Some incidents cited in ''A Higher Form of Killing: The Secret History of Chemical and Biological Warfare'' are as follows: *Four pipe fitters had liquid Tabun drain onto them and died before their rubber suits could be removed. *A worker had two liters of Tabun pour down the neck of his rubber suit. He died within two minutes. *Seven workers were hit in the face with a stream of Tabun of such force that the liquid was forced behind their respirators. Only two survived despite

resuscitation Resuscitation is the process of correcting physiological disorders (such as lack of breathing or heartbeat) in an Acute (medicine), acutely ill patient. It is an important part of intensive care medicine, anesthesiology, trauma surgery and emerg ...

measures. and moved, probably to Dzerzhinsk,

USSR The Union of Soviet Socialist Republics. (USSR), commonly known as the Soviet Union, was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 until Dissolution of the Soviet ...

. In 1940 the German Army Weapons Office ordered the mass production of Sarin for wartime use. A number of pilot plants were built and a high-production facility was under construction (but was not finished) by the end of

World War II World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...

. Estimates for total Sarin production by Nazi Germany range from 500 kg to 10

ton Ton is any of several units of measure of mass, volume or force. It has a long history and has acquired several meanings and uses. As a unit of mass, ''ton'' can mean: * the '' long ton'', which is * the ''tonne'', also called the ''metric ...

s. During that time, German

intelligence Intelligence has been defined in many ways: the capacity for abstraction, logic, understanding, self-awareness, learning, emotional knowledge, reasoning, planning, creativity, critical thinking, and problem-solving. It can be described as t ...

believed that the

Allies An alliance is a relationship among people, groups, or states that have joined together for mutual benefit or to achieve some common purpose, whether or not an explicit agreement has been worked out among them. Members of an alliance are calle ...

also knew of these compounds, assuming that because these compounds were not discussed in the Allies' scientific journals information about them was being suppressed. Though Sarin, Tabun and Soman were incorporated into

artillery Artillery consists of ranged weapons that launch Ammunition, munitions far beyond the range and power of infantry firearms. Early artillery development focused on the ability to breach defensive walls and fortifications during sieges, and l ...

shells, the German government ultimately decided not to use nerve agents against Allied targets. The Allies did not learn of these agents until shells filled with them were captured towards the end of the war. German forces used chemical warfare against partisans during the

Battle of the Kerch Peninsula The Battle of the Kerch Peninsula, which commenced with the Soviet Kerch-Feodosia Landing Operation () and ended with the German Operation Bustard Hunt (), was a World War II battle between Erich von Manstein's Nazi Germany, German and Kingdom o ...

in 1942, but did not use any nerve agent. This is detailed in Joseph Borkin's book ''The Crime and Punishment of IG Farben'':

Post–World War II

Since World War II, Iraq's use of mustard gas against Iranian troops and

Kurds Kurds (), or the Kurdish people, are an Iranian peoples, Iranic ethnic group from West Asia. They are indigenous to Kurdistan, which is a geographic region spanning southeastern Turkey, northwestern Iran, northern Iraq, and northeastern Syri ...

(

Iran–Iraq War The Iran–Iraq War, also known as the First Gulf War, was an armed conflict between Iran and Iraq that lasted from September 1980 to August 1988. Active hostilities began with the Iraqi invasion of Iran and lasted for nearly eight years, unti ...

of 1980–1988) has been the only large-scale use of any chemical weapons. On the scale of the single Kurdish village of

Halabja Halabja (, ) is a city in the Kurdistan Region of Iraq and the capital of Halabja Governorate, located about northeast of Baghdad and from the Iranian border. The city lies at the base of what is often referred to as the greater Hewraman re ...

within its own territory, Iraqi forces did expose the populace to some kind of chemical weapons, possibly mustard gas and most likely nerve agents. Operatives of the

Aum Shinrikyo , better known by their former name , is a Japanese new religions, Japanese new religious movement and doomsday cult founded by Shoko Asahara in 1987. It carried out the deadly Tokyo subway sarin attack in 1995 and was found to have been respo ...

religious group made and used

Sarin Sarin (NATO designation GB nerve_agent#G-series.html" ;"title="hort for nerve agent#G-series">G-series, "B" is an extremely toxic organophosphorus compound.Tokyo subway sarin attack The was a Chemical terrorism, chemical domestic terrorism, domestic terrorist attack perpetrated on 20 March 1995, in Tokyo, Japan, by members of the Aum Shinrikyo cult. In five coordinated attacks, the perpetrators released sarin on three line ...

. In the

Gulf War , combatant2 = , commander1 = , commander2 = , strength1 = Over 950,000 soldiers3,113 tanks1,800 aircraft2,200 artillery systems , page = https://www.govinfo.gov/content/pkg/GAOREPORTS-PEMD-96- ...

, no nerve agents (nor other chemical weapons) were used, but a number of U.S. and UK personnel were exposed to them when the Khamisiyah chemical depot was destroyed. This and the widespread use of anticholinergic drugs as a protective treatment against any possible nerve gas attack have been proposed as a possible cause of Gulf War syndrome.

Sarin Sarin (NATO designation GB nerve_agent#G-series.html" ;"title="hort for nerve agent#G-series">G-series, "B" is an extremely toxic organophosphorus compound.a 2013 attack on Ghouta during the Syrian Civil War, killing several hundred people. Most governments contend that forces loyal to President

Bashar al-Assad Bashar al-Assad (born 11September 1965) is a Syrian politician, military officer and former dictator Sources characterising Assad as a dictator: who served as the president of Syria from 2000 until fall of the Assad regime, his government ...

deployed the gas; however, the

Syrian Government The government of Syria takes place in a presidential system and is currently in a transitionary period under and led by a transitional government. The seat of the government is located in Damascus, Syria. On 8 December 2024, after the succ ...

has denied responsibility. On 13 February 2017, the nerve agent VX was used in the assassination of Kim Jong-nam, half-brother of the North Korean leader

Kim Jong-un Kim Jong Un (born 8 January 1983 or 1984) is a North Korean politician and dictator who has served as supreme leader of North Korea since 2011 and general secretary of the Workers' Party of Korea (WPK) since 2012. He is the third son of Kim ...

, at

Kuala Lumpur International Airport Kuala Lumpur International Airport is the main international airport serving Kuala Lumpur, the capital of Malaysia. It is located in the Sepang District of Selangor, approximately south of downtown Kuala Lumpur and serves the Greater Kuala L ...

in

Malaysia Malaysia is a country in Southeast Asia. Featuring the Tanjung Piai, southernmost point of continental Eurasia, it is a federation, federal constitutional monarchy consisting of States and federal territories of Malaysia, 13 states and thre ...

. On 4 March 2018, a former Russian agent (who was convicted of high treason but allowed to live in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...

via a spy swap agreement), Sergei Skripal, and his daughter, who was visiting from Moscow, were both poisoned by a Novichok nerve agent in the English city of

Salisbury Salisbury ( , ) is a city status in the United Kingdom, cathedral city and civil parish in Wiltshire, England with a population of 41,820, at the confluence of the rivers River Avon, Hampshire, Avon, River Nadder, Nadder and River Bourne, Wi ...

. They survived, and were subsequently released from hospital. In addition, a

Wiltshire Police Wiltshire Police, formerly known as Wiltshire Constabulary, is the territorial police force responsible for policing the county of Wiltshire (including the Borough of Swindon) in South West England. The force serves 722,000 people over an area ...

officer, Nick Bailey, was exposed to the substance. He was one of the first to respond to the incident. Twenty-one members of the public received medical treatment following exposure to the nerve agent. Despite this, only Bailey and the Skripals remained in critical condition. On 11 March 2018,

Public Health England Public Health England (PHE) was an executive agency of the Department of Health and Social Care in England which began operating on 1 April 2013 to protect and improve health and wellbeing and reduce health inequalities. Its formation came as a ...

issued advice for the other people believed to have been in the Mill pub (the location where the attack is believed to have been carried out) or the nearby

Zizzi Zizzi Restaurants Limited, trading as Zizzi, is a chain of Italian-inspired restaurants in the United Kingdom and Ireland. It is the sister restaurant of ASK Italian, both having been founded by Adam Kaye, Adam and Sam Kaye. In February 2015, Bri ...

Restaurant. On 12 March 2018, British Prime Minister

Theresa May Theresa Mary May, Baroness May of Maidenhead (; ; born 1 October 1956), is a British politician who served as Prime Minister of the United Kingdom and Leader of the Conservative Party from 2016 to 2019. She previously served as Home Secretar ...

stated that the substance used was a Novichok nerve agent. On 30 June 2018, two British nationals, Charlie Rowley and Dawn Sturgess, were poisoned by a Novichok nerve agent of the same kind that was used in the Skripal poisoning, which Rowley had found in a discarded perfume bottle and gifted to Sturgess. Whilst Rowley survived, Sturgess died on 8 July. Metropolitan Police believe that the poisoning was not a targeted attack, but a result of the way the nerve agent was disposed of after the poisoning in Salisbury.

Ocean disposal

In 1972, the United States Congress banned the practice of disposing chemical weapons into the ocean. Thirty-two thousand

ton Ton is any of several units of measure of mass, volume or force. It has a long history and has acquired several meanings and uses. As a unit of mass, ''ton'' can mean: * the '' long ton'', which is * the ''tonne'', also called the ''metric ...

s of nerve and mustard agents had already been dumped into the ocean waters off the United States by the U.S. Army, primarily as part of Operation CHASE. According to a 1998 report by William Brankowitz, a deputy project manager in the U.S. Army Chemical Materials Agency, the Army created at least 26 chemical weapons dump sites in the ocean off at least 11 states on both the west and east coasts. Due to poor records, they currently only know the rough whereabouts of half of them. There is currently a lack of scientific data regarding the ecological and health effects of this dumping. In the event of leakage, many nerve agents are soluble in water and would dissolve in a few days, while other substances like

sulfur mustard Mustard gas or sulfur mustard are names commonly used for the organosulfur chemical compound bis(2-chloroethyl) sulfide, which has the chemical structure S(CH2CH2Cl)2, as well as other species. In the wider sense, compounds with the substituen ...

could last longer. There have also been a few incidents of chemical weapons washing ashore or being accidentally retrieved, for example during dredging or trawl fishing operations.

Detection

Detection of gaseous nerve agents

The methods of detecting gaseous nerve agents include but are not limited to the following.

Laser photoacoustic spectroscopy

Laser A laser is a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation. The word ''laser'' originated as an acronym for light amplification by stimulated emission of radi ...

photoacoustic spectroscopy (LPAS) is a method that has been used to detect nerve agents in the air. In this method, laser light is absorbed by gaseous

matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are ultimately composed of atoms, which are made up of interacting subatomic pa ...

. This causes a heating/cooling cycle and changes in

pressure Pressure (symbol: ''p'' or ''P'') is the force applied perpendicular to the surface of an object per unit area over which that force is distributed. Gauge pressure (also spelled ''gage'' pressure)The preferred spelling varies by country and eve ...

. Sensitive

microphones A microphone, colloquially called a mic (), or mike, is a transducer that converts sound into an electrical signal. Microphones are used in many applications such as telephones, hearing aids, public address systems for concert halls and publi ...

convey

sound waves In physics, sound is a vibration that propagates as an acoustic wave through a transmission medium such as a gas, liquid or solid. In human physiology and psychology, sound is the ''reception'' of such waves and their ''perception'' by the br ...

that result from the pressure changes. Scientists at the U.S. Army Research Laboratory engineered an LPAS system that can detect multiple trace amounts of toxic gases in one air sample. This

technology Technology is the application of Conceptual model, conceptual knowledge to achieve practical goals, especially in a reproducible way. The word ''technology'' can also mean the products resulting from such efforts, including both tangible too ...

contained three lasers

modulated Signal modulation is the process of varying one or more properties of a periodic waveform in electronics and telecommunication for the purpose of transmitting information. The process encodes information in form of the modulation or message ...

to different

frequency Frequency is the number of occurrences of a repeating event per unit of time. Frequency is an important parameter used in science and engineering to specify the rate of oscillatory and vibratory phenomena, such as mechanical vibrations, audio ...

, each producing a different sound wave tone. The different wavelengths of light were directed into a sensor referred to as the photoacoustic cell. Within the cell were the vapors of different nerve agents. The traces of each nerve agent had a signature effect on the "loudness" of the lasers' sound wave tones. Some overlap of nerve agents' effects did occur in the acoustic results. However, it was predicted that specificity would increase as additional lasers with unique wavelengths were added. Yet, too many lasers set to different

wavelengths In physics and mathematics, wavelength or spatial period of a wave or periodic function is the distance over which the wave's shape repeats. In other words, it is the distance between consecutive corresponding points of the same '' phase'' on ...

could result in overlap of

absorption spectra Absorption may refer to: Chemistry and biology * Absorption (biology), digestion ** Absorption (small intestine) * Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials * Absorption (skin), a route by whic ...

. Citation LPAS technology can identify

gases Gas is a state of matter that has neither a fixed volume nor a fixed shape and is a compressible fluid. A ''pure gas'' is made up of individual atoms (e.g. a noble gas like neon) or molecules of either a single type of atom ( elements such ...

in

parts per billion In science and engineering, the parts-per notation is a set of pseudo-units to describe the small values of miscellaneous dimensionless quantities, e.g. mole fraction or mass fraction. Since these fractions are quantity-per-quantity measur ...

(ppb) concentrations. The following nerve agent simulants have been identified with this multiwavelength LPAS: * dimethyl methyl phosphonate (DMMP) * diethyl methyl phosphonate (DEMP) * diisopropyl methyl phosphonate (DIMP) * dimethylpolysiloxane (DIME), triethyl phosphate (TEP) * tributyl phosphate (TBP) * two volatile organic compounds (VOCs) *

acetone Acetone (2-propanone or dimethyl ketone) is an organic compound with the chemical formula, formula . It is the simplest and smallest ketone (). It is a colorless, highly Volatile organic compound, volatile, and flammable liquid with a charact ...

(ACE) *

isopropanol Isopropyl alcohol (IUPAC name propan-2-ol and also called isopropanol or 2-propanol) is a colorless, flammable, organic compound with a pungent alcoholic odor. Isopropyl alcohol, an organic polar molecule, is miscible in water, ethanol, an ...

(ISO), used to construct

Sarin Sarin (NATO designation GB nerve_agent#G-series.html" ;"title="hort for nerve agent#G-series">G-series, "B" is an extremely toxic organophosphorus compound. * CO₂

Carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...

*

Benzene Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...

* Formaldehyde * Acetaldehyde * Ammonia * NOx Nitrogen oxide * SO₂ Sulphur oxide * Ethylene Glycol * TATP * TNT

Non-dispersive infrared

Nondispersive infrared sensor, Non-dispersive infrared techniques have been reported to be used for gaseous nerve agent detection.

IR absorption

Traditional Infrared spectroscopy, IR absorption has been reported to detect gaseous nerve agents.

Fourier transform infrared spectroscopy

Fourier-transform infrared spectroscopy, Fourier transform infrared (FTIR) spectroscopy has been reported to detect gaseous nerve agents.

References

Sources

* *

External links

ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Pesticides and Chemical Warfare Nerve Agents
U.S. Department of Health and Human Services * Nervegas: America's Fifteen-year Struggle for Modern Chemical Weapon
Army Chemical Review
* History Note: The CWS Effort to Obtain German Chemical Weapons for Retaliation Against Japa
CBIAC Newsletter

AChE inhibitors and substrates
�
2wfz2wg02wg11som
in Proteopedia {{Acetylcholine metabolism and transport modulators Nerve agents, Acetylcholinesterase inhibitors