VX
| Structural formula | ||||||||||
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| 1: 1 mixture of the ( R ) -form (left) and the ( S ) -form (right) | ||||||||||
| General | ||||||||||
| Surname | VX | |||||||||
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| Molecular formula | C 11 H 26 NO 2 PS | |||||||||
| Brief description |
colorless and odorless, oily liquid |
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| properties | ||||||||||
| Molar mass | 267.37 g mol −1 | |||||||||
| Physical state |
liquid |
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| density |
1.01 g cm −3 |
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| Melting point |
−38.2 ° C |
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| boiling point |
298 ° C (decomposition) |
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| Vapor pressure |
0.014 Pa (20 ° C) |
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| solubility |
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| Toxicological data | ||||||||||
| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||
The substance VX (TX 60 , O -ethyl- S -2-diisopropylaminoethylmethylphosphonothiolate, Edgewood Arsenal Code EA 1701) is a chemical warfare agent and belongs to the V series (V for viscous ) within the neurotoxins .
VX enters the body through the skin, eyes, and respiratory tract and initially causes coughing and nausea. Then it paralyzes the respiratory muscles and leads to death within a few minutes with severe cramps and pain.
Manufacturing and structure
For the synthesis of VX, O -ethyl- O -2-diisopropylaminoethylmethylphosphonite ( CAS : 57856-11-8) is reacted with sulfur . VX is thus a binary warfare agent that can easily be generated from the two precursor substances (e.g. in a warfare agent grenade by simply mixing the components when firing).
VX has a stereocenter on the phosphorus atom, so there are two enantiomers in ( R ) and ( S ) configuration. Both isomers differ greatly in their toxicity. The more toxic isomer is ( S ) -VX [(-) - VX], which is about 1.6 times more toxic than racemic (±) -VX. Customary manufacturing processes produce racemic VX, that is to say a 1: 1 mixture of ( R ) - O -ethyl- S -2-diisopropylamino-ethylmethylphosphonothiolate and ( S ) -O -ethyl- S -2-diisopropylamino-ethylmethylphosphonothiolate.
properties
In its pure form it is a colorless and odorless liquid that is often slightly yellowish due to impurities. Depending on the manufacturing process and purity, VX can have a faint odor of putrid fish and mercaptan .
While nerve agents of the G series (G for Germany ) such as tabun (GA) or sarin (GB) evaporate within hours or days, VX has a much greater persistence . The volatility of VX is about 2000 times less compared to sarin. VX can remain on site for weeks under suitable conditions and is also significantly more toxic than the G-series warfare agents.
Of the industrially produced chemical warfare agents VX is the highest with the toxicity . Only some toxins are significantly more toxic; However, as ABO (Agents of Biological Origin), by definition, these do not count among the C, but rather the B warfare agents, even if they are regulated in the Chemical Weapons Convention .
hydrolysis
In the acidic pH range, diisopropylaminoethanethiol is split off and the toxicologically comparatively harmless methanephosphonic acid monoethyl ester is formed. The basic hydrolysis in the pH range from pH 7-10, on the other hand, leads to the methane phosphonic acid diisopropylaminoethanethiol ester (EA 2192) or its salt, with elimination of the ethoxy radical.
EA 2192 and its salts are also extremely toxic and, like VX, act as cholinesterase inhibitors. The toxicity of EA 2192 is only about 2-3 times less than the toxicity of VX. In contrast to VX, EA 2192 is hardly absorbed through the skin. EA 2192 and its salts are solids and cannot be easily detected by gas chromatography.
effect
VX is mainly absorbed through the skin, since VX is considered a sedentary warfare agent due to its extremely low vapor pressure ; only in the case of application as an aerosol is there a relevant risk through absorption via the respiratory tract. Contamination can only be prevented by adequate individual protection. Once absorbed into the body, VX blocks acetylcholinesterase in the synapses of the parasympathetic autonomic nervous system , the acetylcholine-mediated synapses of the sympathetic part of the autonomic nervous system ( sympathetic nervous system ) and at the neuromuscular endplate ( motor endplate ). This leads to an increase in the neurotransmitter acetylcholine (ACh) in the synapse and thus to permanent irritation of the affected nerves.
As a result, depending on the level of poisoning, the following symptoms occur: runny nose, visual disturbances, pupil constriction, eye pain, shortness of breath, salivation, muscle twitching and cramps, sweating, vomiting, uncontrollable stool, unconsciousness, central and peripheral respiratory paralysis and ultimately death. The effect on the eye occurs even at lower concentrations than the effect on the respiratory tract . Therefore, accommodation disorders and miosis already occur at concentrations and exposure times at which other signs of intoxication cannot yet be observed.
The LD 50 value for an average adult is around 1 mg for respiratory absorption (via the airways) and 10 mg for absorption through the skin. However, deaths have also been described after consumption of significantly lower doses (4 μg / kg orally and 86 μg / kg dermal ).
The effect is similar to that of other organophosphorus compounds such as tabun , soman and sarin , but also of various insecticides such as parathion (E605). Other pesticides are based on the same principle of action, but are orders of magnitude more effective on insects than on humans. Examples are malathion , disulfoton and similar substances.
Optical isomers
The toxicity depends on the stereochemistry at the P atom. The following LD 50 values were determined in mice for intravenous administration :
( RS ) -VX [(±) -VX]: 20.1 µg / kg
( S ) -VX [(-) - VX]: 12.6 µg / kg
( R ) -VX [(+) - VX]: 165 µg / kg
Human studies with VX
From 1959 onwards, numerous human experiments were carried out with racemic (±) -VX, in which the toxicity and the effect of various types of application (intravenous, oral, percutaneous, inhalative) were examined.
Intravenous administration : According to the tests, the first physiological effects such as headache, drowsiness, sweating and abdominal cramps occur in the dose range of 0.06–0.1 µg / kg (that is about 5–10 micrograms for a man weighing 80–90 kg). 1.3–1.5 µg / kg (104–135 µg) lead to dizziness, tremors, drowsiness, severe nausea, vomiting and abdominal cramps. In this dose range, the activity of cholinesterase falls to 45-17% within 15 minutes. The cholinesterase is regenerated for the first 1–2 days at a rate of around 1% per hour. Amounts in the range of about 150–210 µg lead to a cholinesterase inhibition of about 85% and to extensive incapacity to act with partial loss of contact with the environment.
Percutaneous application : Percutaneously 5–35 µg / kg (approx. 0.4–3 mg) lead to sweating, tiredness, weakness, nausea, vomiting and headache. When absorbed through the skin, the first symptoms appear very delayed, depending on the location of application, within 5–10 hours after skin contact. Experiments with radioactively labeled VX ( 32 P) show that less than 1% is absorbed through the palm of the hand, around 8% through the skin on the back and 15% through the forearms.
Oral application : Oral amounts of 0.2–0.4 mg lead to an inhibition of cholinesterase by 50–80%.
therapy
Atropine is one way of competitively interrupting the effect on the muscarinic acetylcholine receptors in the case of VX poisoning . It must be given approximately every ten minutes at a dose of 2–5 mg. In addition, obidoxime chloride must be given to reactivate the acetylcholinesterase . However, the oxime therapy is only successful with VX a short time after the poisoning, since after binding to the cholinesterase, an alkoxy residue is split off from the organophosphate - the bound VX - through reaction with water, which is referred to as "aging".
Discovery and Dissemination
The phosphorylthiocholine class was independently discovered by Ranaji Goshem of Imperial Chemical Industries Limited (USA) and Lars-Erik Tammelin of the Swedish Defense Research Institute in 1952.
1955 the first "V" warfare agent VG (Amiton) was produced. Later far more toxic substances were not developed in this group, such as VM , VE and VS .
VX was also produced by the United States until the 1997 Chemical Weapons Convention was signed, which required the destruction of all supplies . The Soviet Union had a chemically very closely related substance ( VR - or "Russian VX").
Application / use
It is controversial whether Saddam Hussein used VX against the Kurdish population in the 1988 poison gas attack on Halabja in northern Iraq. Around 5,000 people, mostly children, women and old men, died in agony in the attack. Many thousands more died afterwards or suffered permanent health problems.
On February 13, 2017, Kim Jong-nam , the half-brother of North Korean President Kim Jong-un and son of Kim Jong-il , was allegedly murdered with VX in an attack at Kuala Lumpur airport. According to the autopsy report, residues of this nerve agent were found in him, which led to death within a few minutes. An expert later also found traces of VX on the T-shirt of one of the two defendants.
Analytics
VX can be reliably detected in various test materials such as blood samples, urine, soil samples or drinking water after appropriate sample preparation by HPLC, also coupled with mass spectrometry .
See also
Web links
- Spiez Laboratory: Data sheet VX (PDF file; 194 kB)
- Saskia Eckert: Development of a dynamic model to study the protective effects of reversible acetylcholinesterase inhibitors against irreversible inhibition by highly toxic organophosphates . Munich 2006, DNB 982657064 , urn : nbn: de: bvb: 19-61966 (dissertation, University of Munich).
Individual evidence
- ^ A b c D. H. Ellison: Handbook of Chemical and Biological Warfare Agents. 2nd Edition. CRC Press, 2007, ISBN 978-0-8493-1434-6 , p. 27.
- ↑ a b c d Entry on VX. In: Römpp Online . Georg Thieme Verlag, accessed on December 25, 2014.
- ↑ a b c d e f Entry on VX in the ChemIDplus database of the United States National Library of Medicine (NLM)
- ^ A b Günter Hommel: Handbook of dangerous goods. Volume 6, Springer, Berlin / Heidelberg 2012, ISBN 978-3-642-25051-4 , p. 2286.
- ^ Neurotoxicology . Vol. 7, 1986, p. 225.
- ↑ a b Appendix D: Health Risk Assessment for the Nerve Agent Vx . In: Journal of Toxicology and Environmental Health , Part A . tape 59 , no. 5-6 , 2000, pp. 439-469 , doi : 10.1080 / 713852146 .
- ↑ JS Wiles, TB Alexander: Comparative toxicity of VX applied to the unclipped and clipped skin of bare and clothed rabbits . AD839329. US Army Chemical Research and Development Laboratories, Aberdeen Proving Ground, MD 1960.
- ^ Steven L. Hoenig: Compendium of Chemical Warfare Agents . Springer Science & Business Media, New York 2006, ISBN 0-387-69260-6 , pp. 162 ( limited preview in Google Book search).
- ↑ a b William S. Augerson: Chemical and Biological Warfare Agents (= Gulf War illnesses series . Band 5 ). Rand, Santa Monica, CA 2000, ISBN 978-0-8330-2680-4 , pp. 201 ( health.mil [PDF]).
- ↑ David J. McGarvey, William R. Creasy, Jill L. Ruth, Kevin M. Morrissey, John R. Stuff: Chemical Analysis and Reaction Kinetics of EA-2192 in Decontamination Solution for the MMD-1 Project . ADA416809. May 2003 ( dtic.mil [PDF]).
- ↑ Frederick R. Sidell, William A. Groff: The reactivatibility of cholinesterase inhibited by VX and sarin in man . In: Toxicology and Applied Pharmacology . tape 27 , no. 2 , 1974, p. 241-252 , doi : 10.1016 / 0041-008X (74) 90195-1 .
- ↑ Twenty-third report (= Technical report series . Volume 23 , no. 463 ). World Health Organization, Geneva, Switzerland 1970, OCLC 56103048 , p. 24 ( who.int [PDF]).
- ^ HP Benschop, LPA De Jong: Nerve agent stereoisomers: analysis, isolation and toxicology. In: Acc. Chem. Res. Volume 21 , no. 10 , 1988, pp. 368-374 , doi : 10.1021 / ar00154a003 .
- ↑ a b c Timothy C. Marrs; Robert L. Maynard; Frederick R. Sidell: Chemical Warefare Agents - Toxicology and Treatment . John Wiley & Sons, Chichester 1998, ISBN 0-471-95994-4 , pp. 243 .
- ↑ Klaus Aktories, Ulrich Förstermann, Franz Hofmann, Klaus Starke (eds.): General and special pharmacology and toxicology . 11., revised. Edition. Elsevier, Urban & Fischer, Munich 2013, ISBN 978-3-437-42523-3 , pp. 1058 .
- ↑ Eric Croddy, James J. Wirtz (eds.): Weapons of mass destruction: an encyclopedia of worldwide policy, technology and history. Volume 2, ISBN 1-85109-490-3 , p. 313. ( Limited preview in Google Book Search)
- ^ Nerve Agents - Lethal organo-phosphorus compounds inhibiting cholinesterase. (No longer available online.) In: Organization for the Prohibition of Chemical Weapons website. Archived from the original on September 27, 2008 ; Retrieved October 7, 2006 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.
- ^ Nerve Agents: General. (No longer available online.) In: The site for information about chemical and biological weapons for emergency, safety and security personnel. Archived from the original on October 12, 2006 ; Retrieved October 7, 2006 .
- ↑ Stephen C. Pelletiere: A War Crime Or an Act of War? ( Page no longer available , search in web archives ) Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. . In: New York Times . January 31, 2003.
- ↑ Investigators find neurotoxins on Kim Jong Nam's body. on: Spiegel online. accessed on February 24, 2017.
- ↑ Fabian Kretschmer: The agonizing death of Kim Jong-nam by nerve gas VX. In: The Standard . February 24, 2017.
- ↑ Kim Jong Nam murder case: nerve gas discovered on T-shirt of defendant . In: Spiegel Online . October 5, 2017 ( spiegel.de [accessed October 5, 2017]).
- ↑ SJ Stubbs, RW Read: Liquid chromatography tandem mass spectrometry applied to quantitation of the organophosphorus nerve agent VX in microdialysates from blood probes. In: J Chromatogr B Analyt Technol Biomed Life Sci. 878 (17-18), May 15, 2010, pp. 1253-1256. PMID 20034857
- ↑ G. Reiter, J. Mikler, I. Hill, K. Weatherby, H. Thiermann, F. Worek: Simultaneous quantification of VX and its toxic metabolite in blood and plasma samples and its application for in vivo and in vitro toxicological studies. In: J Chromatogr B Analyt Technol Biomed Life Sci. 879 (26), Sep 15, 2011, pp. 2704-2713. PMID 21862421
- ↑ BS Crow, BG Pantazides, J. Quiñones-González, JW Garton, MD Carter, JW Perez, CM Watson, DJ Tomcik, MD Crenshaw, BN Brewer, JR Riches, SJ Stubbs, RW Read, RA Evans, JD Thomas, TA Blake, RC Johnson: Simultaneous measurement of tabun, sarin, soman, cyclosarin, VR, VX, and VM adducts to tyrosine in blood products by isotope dilution UHPLC-MS / MS. In: Anal Chem. 86 (20), Oct 21, 2014, pp. 10397-10405. PMID 25286390
- ↑ JR Barr, WJ Driskell, LS Aston, RA Martinez: Quantitation of metabolites of the nerve agents sarin, soman, cyclohexylsarin, VX, and Russian VX in human urine using isotope-dilution gas chromatography-tandem mass spectrometry. In: J Anal Toxicol. 28 (5), Jul-Aug 2004, pp. 372-378. PMID 15239858
- ↑ MR Gravett, FB Hopkins, AJ Self, AJ Webb, CM Timperley, JR Riches: Fate of the chemical warfare agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX) on soil following accelerant-based fire and liquid decontamination. In: Anal Bioanal Chem. 406 (21), Aug 2014, pp. 5121-5135. PMID 24972874
- ↑ JS Knaack, Y. Zhou, M. Magnuson, E. Silvestri, RC Johnson: Performance of a novel high throughput method for the determination of VX in drinking water samples. In: Anal Chem. 85 (5), Mar 5, 2013, pp. 2611-2616. PMID 23402290
