VX
Gas
VX is an extremely toxic synthetic chemical compound in the organophosphorus class, specifically, a thiophosphonate. In the class of nerve agents, it was developed for military use in chemical warfare after translation of earlier discoveries of organophosphate toxicity in pesticide research. In its pure form, VX is a colorless, relatively non-volatile liquid, taking on a yellowish to brown color when impure.[4] Because of its low volatility, VX persists in environments where it is dispersed.[4]
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VX, short for "venomous agent X",[5] is the best known of Tammelin's esters, named for the member of the Swedish National Defence Research Institute who first studied them; now one of a broader V-series of agents, they are classified as nerve agents and have been used as a chemical weapon in various recorded deadly attacks. VX fatalities occur with exposure to low to tens of milligram quantities via inhalation or absorption through skin; VX is thus more potent than sarin, another nerve agent with a similar mechanism of action. On such exposure, these agents severely disrupt the body's signaling between the nervous and muscular systems, leading to a prolonged neuromuscular blockade, flaccid paralysis of all the muscles in the body including the diaphragm, and death by asphyxiation.[6]
The danger of VX, in particular, lies in direct exposure to agent persisting where it was dispersed, and not through its evaporating and being distributed as a vapor (i.e., it is not a "vapor hazard").
VX is considered an area denial weapon due to these physical and biochemical characteristics.[7] As a chemical weapon, it is categorized as a weapon of mass destruction and is banned by the Chemical Weapons Convention of 1993,[8] where production and stockpiling of VX exceeding 100 grams (3.53 oz) per year is outlawed. The only exception is for "research, medical or pharmaceutical purposes outside a single small-scale facility in aggregate quantities not exceeding 10 kg [22 lb] per year per facility".[9]
Physical properties
It is of low molecular weight (FW 267), a liquid under standard and ambient temperate and tropical environmental conditions at most times (m.p. about −51°C),[10] with a density about that of water.[11] It is relatively hydrophobic—with about 100-fold more partitioning into octanol, over water, in this biphase[citation needed]—and is relatively high boiling (b.p. about 300°C).[12] In this regard, as a chemical warfare agent, its physical properties are considered somewhat exceptional, for instance, in that its low volatility gives it a high persistence in the environment.[13]
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VX is odorless and tasteless,[14] and can be dispersed as a liquid, as an aerosol, or as a mixture with a clay or talc in the form of thickened agent.[13]
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Mechanism of action
VX is an acetylcholinesterase inhibitor, i.e., it works by blocking the function of the enzyme known as acetylcholinesterase (AChE). Normally, when a motor neuron is stimulated, it releases a neurotransmitter into the space between the neuron and an adjacent muscle cell; that neurotransmitter is the chemical compound acetylcholine (ACh, abbreviation not used here, for clarity). When this acetylcholine is taken up by the muscle cell, it stimulates muscle contraction. To avoid a state of constant muscle contraction, the acetylcholine is then broken down (hydrolysed) into the inactive substances, acetic acid and choline, by the AChe enzyme. VX blocks the action of AChe, resulting in an accumulation of acetylcholine in the space between the neuron and muscle cell. On a molecular level, this leads to this ongoing stimulation and eventual "fatigue" of all affected muscarinic and nicotinic ACh receptors.
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Clinically, the consequence of ongoing stimulation is uncontrolled muscle contraction. This results in initial violent contractions, followed by "sustained supercontraction restricted to the fluid (sarcoplasm) of the subjunctional endplate and prolonged, depolarizing neuromuscular blockade."[this quote needs a citation]The prolonged blockade results in flaccid paralysis of all the muscles in the body, and it is such sustained paralysis of the diaphragm muscle that causes death by asphyxiation.
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Symptoms of exposure
Early symptoms of percutaneous exposure (skin contact) include local sweating and muscular twitching at the area of exposure, followed by nausea or vomiting. Early symptoms of exposure to VX vapor include rhinorrhea (runny nose) and/or tightness in the chest with shortness of breath (bronchial constriction). Miosis (pinpointing of the pupils) may be an early sign of agent exposure, but is not usually used as the only indicator of exposure.[19]
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Toxicology
VX is a "particularly toxic nerve agent"; as the Federation of American Scientists notes, doses of the agent
[that] are potentially life-threatening may be only slightly larger than those producing least effects. Death usually occurs within 15 minutes after absorption of a fatal VX dosage.[4]
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The median lethal exposure—the exposure required to kill half of a tested population—as estimated for 70 kg human males has been reported: the median lethal dose (LD50) via exposure to the skin is reported to be 10 mg (0.00035 oz), and the lethal concentration time (LCt50), measuring the concentration of the vapor in milligrams per cubic meter (m3) per length of time exposed in minutes, is estimated for VX to be 30–50 mg·min/m3.[4]
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Treatment
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When treating VX exposure, primary consideration is given to removal of the liquid agent from the skin, before removal of the individual to an uncontaminated area or atmosphere.[citation needed] After this, the victim is decontaminated by washing the contaminated areas with household bleach and flushing with clean water, followed by removal of contaminated clothing and further skin decontamination.[citation needed] When possible, decontamination is completed before the casualty is taken for further medical treatment.[citation needed]
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An individual known to have been exposed to a nerve-agent, or who exhibits definite signs or symptoms of nerve-agent exposure are generally given the antidotes atropine and pralidoxime (2-PAM), as well an injected sedative/antiepileptic such as diazepam.[citation needed] In several nations the nerve agent antidotes are issued for military personnel in the form of an autoinjector such as the United States military Mark I NAAK.[19]
Atropine blocks a subset of acetylcholine receptors known as muscarinic acetylcholine receptors (mAchRs), so that the buildup of acetylcholine produced by loss of the acetylcholinesterase function has a reduced effect on their target receptor.[citation needed] 2-PAM reactivates the acetylcholinesterase enzyme (AChE), thus reversing the effects of VX.[citation needed][20]
Ethyl methylphosphonic acid.R1 = ethyl, R2 = methyl.
However, if 2-PAM is not given soon enough, the inactivated enzyme will "age", resulting in a much stronger AChE-phosphate binding, that 2-PAM treatment cannot reverse.[21]The basis of this "aging" process in protein structure—a possible conformational isomerism—has been studied using X-ray crystallography focused on the AChE active site of relevant enzymes, where possible implications for the two enantiomers in the VX chemical agent are also discussed.[22]
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Diagnostic tests
Controlled studies in humans have shown that minimally toxic doses cause 70–75% depression of erythrocyte cholinesterase within several hours of exposure. The serum level of ethyl methylphosphonic acid (EMPA), a VX hydrolysis product, was measured to confirm exposure in one poisoning victim. There also exist procedures for determination of VX hydrolysis products in urine and of VX adducts to albumin in blood.[23]
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