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Nerve Agents: What are they?

March 8, 2018

By Dan Kaszeta

The former Russian intelligence officer Sergei Skripal and his daughter have been deliberately poisoned, in an apparent act of chemical terrorism.  This  poisoning occurred in Salisbury, in the UK,  on Sunday 4 March 2018. It has recently been disclosed that this particular act involved the use of a “nerve agent”.  Already, there are numerous examples of misuse of basic technical terms.  The purpose of this post is to provide an overview of nerve agents and the terminology related to them.

Poisons and the nervous system

There are numerous types of chemical and biological substances that can affect the human nervous system. Some might be tempted to apply the phrase “nerve agent” to any of them.   However, this is not consistent with established definitions and usage.  The human nervous system is complex, and there are many complicated mechanisms by which toxic substances of either natural or artificial origin could cause damage to the human nervous system.  For example, nature is full of “neurotoxins” such as tetrodotoxin (found in some fish, like puffer fish), botulinum toxin, and conotoxin (found in shellfish).

It should be be noted that the word toxin has a specific definition which is often abused.  When used on its own, the word toxin means a poison or venom of natural origin, such as plants, microbes, snakes, etc.  When conjoined with other words like cyto- or neuro-  the meaning is sometimes extended to include substances not of plant or animal origin. For example, the metal lead is considered a neurotoxin, even though it is not produced by a plant or animal

What are “nerve agents”

Nerve agents are a specific family of chemicals. The term “nerve agent” has specific definitions in military, scientific, and medical literature and the so-called “nerve agents” are a subset of the broader category that we could broadly call “bad things that affect the nervous system.”   The reference documents that I have checked all consistently define “nerve agents” as chemicals that interfere with the normal operations of the chemicals acetylcholine and acetylcholinesterase in the human nervous system.  Some sources go as far as to restrict the definition to chemicals in the organophosphate family. However, there is a strong case to be made that chemicals in the related carbamate family could be considered nerve agents because their biological action is similar.

All of the nerve agents are difficult to manufacture, and very difficult to manufacture without causing harm or damage. A large, sophisticated laboratory with access to the correct precursors could make small quantities of them, provided the right knowledge is applied.  Large-scale production is very difficult and is largely considered a state-level activity given the size and expense of the required effort.

The human nervous system requires a delicate balance of chemicals to regulate itself.  Nerve agents binds to a chemical known as acetylcholinesterase and, in doing so, disrupt the electrochemical reactions required for the body to operate properly. The binding of acetylcholinesterase leads to a build-up of acetylcholine, which then in turn leads to a syndrome called a cholinergic crisis. In effect, the nervous system starts to over-act and muscles and glands start to work over-time.

This wikipedia index page has a reasonable list of many of the known nerve agents.

What about the term “Nerve Gas” ?

The term “nerve gas” is highly inaccurate. The military nerve agents are all liquids under normal temperatures and conditions.  This is also true with the other nerve agents.  It is even possible that some nerve agents might even be solids at temperatures that are encountered.  For example, the pesticide Parathion, is a solid at low temperatures as its melting point is 6 degrees C.  Its sister compound, Parathion methyl, is solid at room temperature.  None of the nerve agents are gases at room temperatures, although most of them have some time of vapour pressure.

Routes of exposure

There are several ways nerve agents could enter the human body. These are called “routes of exposure” and are as follows:

  • Respiratory: Nerve agent in vapour or aerosol (a finely divided mist of solid or liquid) form can be inhaled.
  • Ocular: Nerve agent can be absorbed by the eyes.
  • Dermal: Absorption through the skin. Primarily from nerve agents in liquid form, or a very high concentration of aerosol or vapour (usually many times higher than that which is lethal through inhalation).
  • Via Wound: Through a disruption in the skin. This would generally only occur if nerve agent in liquid form was on a fragment or sharp object and it entered into the human body. This is a rarely considered in military scenarios but could be relevant in assassination situations.
  • Gastrointestinal: Nerve can enter the body if ingested. This would happen if it was in food or drink, for example.  This is rarely considered in military scenarios, but is relevant in terrorism scenarios.

Nerve agents usually operate quickly through respiratory and ocular exposure, with onset of adverse effects within seconds to a few minutes depending on dose. Absorption through the skin is slower, i.e. minutes to hours, depending on dose. Rate of action for wound exposure is believed to be intermediate in speed between respiratory and dermal absorption. Gastrointestinal absorption is not well documented but is likely to be fast. It has been theorised that nerve agents could be engineered to have delayed onset of effects.

The signs and symptoms, and their order of appearance, vary depending on the route of exposure. The are drawn from the Textbook of Military Medicine volume on chemical warfare agents:

Liquid exposure to skin

Rate of Action: Minutes to hours after exposure

Mild/Moderate: Muscle twitching at site of exposure (fasciculations), sweating, nausea, vomiting, weakness

Serious: Mild symptoms, plus difficulty breathing, generalized muscle twitching, weakness, paralysis, convulsions, loss of bladder and bowel control.

It should be noted that miosis (pinpointing of eye pupils) is often a late sign in situations where the victim is exposed only to liquid.

Inhalation of aerosolized droplets or vapour

Rate of Action: Seconds to minutes after exposure

Mild: Miosis (pinpoint pupils), dimness of vision, headache, runny nose, salivation, tightness in chest

Serious: Mild symptoms, plus difficulty breathing, generalized muscle twitching, weakness, paralysis, convulsions, loss of bladder and bowel control

The phenomenon of ingested nerve agents is less well-studied, so the exact presentation of symptoms and the order in which they are likely to appear is less certain, although, logically,  gastrointestinal effects might be earlier.  The rate of action of nerve agents could theoretically vary.  Some compounds are more fat soluble than others, and this affects the rate of absorption through skin.

Persistence in the environment

Given the wide range of theoretically available chemical compounds in the nerve agent family, the persistency in the environment could range from minutes to years, depending on the compound used, temperature, movement of air, and presence of water.  The nerve agents that are well-documented all react over time with water.

Military nerve agents

A number of nerve agents are ones that historically were developed and produced for military purposes.  The first was Tabun, discovered by accident in Germany in 1936 as part of research into insecticides. Other military nerve agents developed later include Sarin, Soman, and VX. All of these particular nerve agents have differing characteristics.

It is very important to stress that military nerve agents are a subset of the overall family of nerve agents. Not every chemical compound that is conceivably part of the nerve agent family is useful in the context of 20th century chemical warfare planning.  Just because something is highly toxic, that fact alone does not necessarily mean that it makes for a useful chemical warfare agent on the battlefield.  When selecting a nerve agent for use as a battlefield weapon, numerous considerations are important. They include, but are not

  • Toxicity by weight: You would want to create the most effect from the least amount of material, as this reduces the number of shells, bombs, etc. you would need to create the desired effects.
  • Safety in storage: Something that is hard to store or transport would complicate military logistics. For example, a chemical agent that corrodes metal makes long term storage of bombs and shells problematic. This was the case with Sarin.  Special manufacturing techniques and specialty additives were needed to ensure long-term shelf life in US cold war-era Sarin produced in the 1950s.
  • Mass production: Making something in small quantities in a laboratory is not the same as developing industrial scale production. Some nerve agents might not have a viable pathway for mass-production, due to a wide variety of factors.  Even the ones that were mass produced involved extremely complex engineering.
  • Economy: Chemical warfare on a state level requires tons, or even thousands of tons, of stockpiled chemical agents. The overall expense of the effort is, therefore, important.  Some theoretically feasible nerve agents might simply be prohibitively expensive to produce in large quantities.
  • Rate of Action: Generally, a chemical warfare agent that acts quickly is preferred, rather than one with a lot of latency (i.e. a lag time between exposure and onset of effects).  The rapid rate of action of nerve agents is one of the reasons they were seen as preferential to earlier chemical warfare agents like phosgene and sulfur mustard, which had a long latency period.
  • Physical characteristics: A nerve agent that is, effectively, a solid at room temperature, would be seen as possibly useless, compared to ones like Sarin and VX which are liquids. Likewise, not every nerve agent might be easily absorbable through skin.


The Soviet Union developed a new series of nerve agents in the 1970s and 1980s.  The exact nature of these so-called “novichok” agents is still debated and the information on them varies a bit depending on what source you are looking at.  This article in CBRNe World magazine provides useful information. For an interesting discussion and more information, this link is of interest.  Some Novichok agents  of interest include A230 and A232.

Nerve agents that aren’t military agents

Given the Salisbury situation, it is important to note that a nerve agent that had not been mass produced for military purposes was used.  The planning considerations above simply do not apply if you are looking to make some vial-sized quantity of something for a specific act of assassination.   The nerve agent category includes a number of substances, such as Amiton and Parathion which were developed as pesticides, not military weapons.  There are numerous theoretical variants of Sarin such as ethyl Sarin and cycloSarin (briefly pursued by Saddam Hussein’s military).  There are sister compounds of VX, such as VM, VE, and VG.   There would be numerous theoretical ways to create chemical molecules in the nerve agent family.   Given what we know so far about the Salisbury situation, it would be premature to fixate on Sarin or VX.  This is especially true when such a panoply of chemicals is available to state actors who historically developed large chemical weapon inventories.

Ways in which nerve agents could be tailored or modified

A sophisticated laboratory with experience in making nerve agents could work to develop or select or modify a nerve agent in ways that could be interesting. As pointed out above, there are characteristics that are ideal for military battlefield use, but there are other characteristics that could be useful for other purposes, such as pesticide use or criminal acts.  These could be theoretically be achieved by developing a new agent, modifying an existing one, combining agents in cocktails, and/or adding additives.  Some features that are theoretically feasible include:

  • Slower absorption: The rate at which the chemical is absorbed by the human body could be slowed down, or the rate at which the nerve agent binds with acetylcholinesterase could be slowed in some way.
  • Lower volatility: Volatility is the propensity of a solid or liquid to assume a vapour state. None of the nerve agents are particularly volatile. Sarin is the most volatile, relatively speaking, evaporating into vapour in minutes in many conditions.  VX is extremely non-volatile and can remain in liquid form for weeks. A low volatility agent in liquid form would mostly be a contact or ingestion hazard, not a wide area inhalation hazard.
  • Foiling detection: Chemical warfare agent detectors look for certain compounds. An innovative compound may be difficult or impossible to detect with certain categories of equipment.
  • Rapid ageing: All of the nerve agents undergo an ageing process.  By this, I mean that the chemical binding between the nerve agent and acetylcholinesterase ages and becomes irreversible over time. For some nerve agents, like VX and Sarin, it is long period.  For some nerve agents, like Soman, it is very quick.  Once the ageing has occurred, antidotes such as oximes (like 2PAM chloride, used in many nerve agent antidote kits) lose their efficacy.  This category of antidote works by freeing the bound acetylcholine before the ageing process has run its course.  A nerve agent with a slow rate of action but fast ageing time would be resistant to part of the standard medical treatment protocols for nerve agent exposure.
Dan Kaszeta

Dan is the managing director of Strongpoint Security Ltd, and lives and works in London, UK. He has 26 years experience in CBRN response, security, and antiterrorism.

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  1. Luiz G Bresciani

    Dear Sirs
    Respectfully I would like that we should be careful in not start going doing precipitated deductions or insinuated responsibilities against such or others govern, special for the simple fact that the victims was a former member of the intelligence services. Nobody can say for the moment that it terrible act could not be object of a counterintelligence action for incriminate Russia. Think about it. But I will not avoid the others persons that think differently committ errors. Be free for do it.

    • Dan Kaszeta


      My article is technical in nature and makes no suppositions of guilt or innocence of any party, even though I have strong opinions on the subject. If you have some objection to a specific statement in the post that I wrote, please give a specific example.

      thank you,

      The Author

  2. Francesca

    So they’ve identified the toxin, but are treating symptoms rather than providing an antidote
    Hamish de Bretton-Gordon, a former commander of the Army’s chemical, biological, radiological and nuclear regiment, said the comment was ‘significant’.

    Commenting on the possible poison, he said: ‘I don’t think it’s polonium – the incubation period is too long and the decontamination that’s been reported is not the kind you would do for a radioactive isotope.

    ‘If Porton Down are saying they are treating symptoms rather than causes they are doing palliative care.

    ‘If it was a nerve agent they would be given an antidote, which leads me to believe it is probably not a nerve agent.’

    Read more:
    Any comment?

    • DDTea

      Hamish De Bretton Gordon’s should be qualified.

      The usual nerve agent therapies–atropine and oximes–have a time window of effectiveness. As mentioned in Dan’s article, some nerve agents such as Soman undergo rapid “aging” when bound to the acetylcholinesterase active site. This leads to a dead enzyme that cannot be reactivated by oximes. In other words, antidotes are ineffective.

      Atropine cannot be given indefinitely, as it is a poison in its own right. I imagine all that can be done is support the victims’ vital functions until they naturally regenerate enough acetylcholinesterase.

    • Dan Kaszeta

      Well, you can certainly take up Hamish de Bretton Gordon’s comments with him. Also bear in mind, in Hamish’s defence, he was speculating earlier on before it was officially confirmed that a nerve agent was used.

      Also, let me clear up your terminology a bit. You use the word “toxin” incorrectly. If it is a nerve agent, by definition it isn’t a toxin.

      With regards to antidotes. They do not work like magic. Atropine is the first and foremost antidote, and it works to counteract the buildup of acetylcholine. However, it poses problems in its own right and there’s a limit to how much atropine you can give. The second type of antidote is one of a number of different drugs (e.g. pralidoxime, obidoxime, HI-6) that free up the acetylcholinesterase that is bound to the nerve agent. Different nerve agents have different “binding times” – after which the oximes have little or no effect. Our colleague DDTea is exactly correct on this.

      • Francesca

        Luckily Porton Down was so close then, a quick diagnosis and a swift application of atropine

  3. milkshake

    these things are not that difficult to produce. You need well equipped synthetic lab, the kind you can find at major university or a pharma company. You need one experienced chemist and few weeks of work, if the chemist has the right experimental procedure – if not then few more weeks to work it out. The precursors are common, uncontrolled and cheap. One can find remarkable details just by a cursory search. And there is a lot more in the chemical literature. For example it appears that binary Novichok A-232 is from the phosgenoxime family and it takes just 3 synthetic steps to make the binary. The chemistry is not challenging, and if one needs just 100mg at the end and works at 1g scale, the
    accidental intoxication is not to hard to avoid (chemist are used to working with nauseatingly smelly substances and the same hygiene and techniques would apply in this case.)

    (For comparison, polonium production needs a nuclear reactor and automated remotely-controlled dedicated reprocessing plant. There are only two places in the world that make it, enormous capital investment and expertise would be needed to replicate it).

    What would help with the attribution is a careful analysis of trace impurities, which would inform how the thing was made and purified, and isotopic composition of different part of the molecule, done by mass spectroscopy. One can for example distinguish if a part of the molecule was made from corn fermentation-derived alcohol or came from oil or natural gas feedstock.
    Then one would compare it with what is known about the Russian Novichok program.

    • DDTea

      Hi Milkshake, welcome to Bellingcat!

      There’s a part of me that wants to disagree with your assertions, but I have to admit that you’re right: in a well equipped lab, with a skilled synthetic chemist, with access to the precursors, the requisite engineering controls, synthesizing gram scale quantities of chemical warfare agents is generally not difficult. In fact, several commercially-available reagents could pass for chemical warfare agents (e.g., diethylchlorophosphate, methyl triflate, dimethyl sulfate, oxalyl chloride…). These are, after all, compounds that need to be produced on a kilotonne scale, following the usual principles of process chemistry (“operated by a one-armed man who can’t read”).

      According to some reports, Porton Down has acquired samples of Russian precursors used to manufacture Novichok compounds. These will certainly be useful for chemical signature attribution. As for conclusions drawn from isotopic patterns, that would make a lot of assumptions about the supply chain of the precursors, no?

  4. DP

    Mairanovsky and Sudoplatov would be very happy indeed after all their typically Soviet work on finding ways to kill innocent people as quickly as possible….Lenin , Stalin and now Putin ….one gets the impression that Russians just love to suffer ….

  5. Francesca

    For you Dan
    Can you verify that the Novichok group of nerve agents is included in the OPCW’s list of prohibited chemicals?
    I am having trouble finding it
    As you are the expert perhaps you would be so kind?

    • Dan Kaszeta

      The Novichok agents are not listed in the CWC schedules. One can read several things into that. First, they were not widely known at the time the CWC was being negotiated. (It was a long process.) Second, among the few (intelligence agencies, etc.) who knew of their existence, there was probably concern that by specifying the in exact detail it would give some countries bad ideas. Third, you must understand the the USSR and thence Russia were actively involved in the negotiations of the CWC. And we now know that one of the many motivations behind the development of Novichoks was specifically to evade arms control provisions. Read into that what you wish, but since the USSR clearly invented them, the burden on them was to disclose this and put them on the list, and they didn’t do it, knowing full well that these compounds existed.

      Whether or not they are specifically mentioned in the lists of scheduled compounds, their development, production, stockpiling is still prohibited by article 1 of the CWC. You can see for yourself.

      • Francesca

        Whether or not the USSR mentioned them,Knowledge of them was most certainly brought to the States along with Vil Mirzayanov.
        In fact , he published a book along with the formulas for Novichoks.
        Is he full of shit?He is certainly being given a lot of credence
        He says Russia must have made the Novichoks found in Salisbury or someone who has read his book
        Anyway, would not the onus be on the US having discovered the existence of the Novichok class, through Mirzayanov, and quite probably many of the chemists who left the collapsed Soviet Union, to alert the OPCW?
        Chemicals can be added to the schedule regularly
        Porton Down says it has identified the nerve agent as being one of the Novichok class. Is this the first time a sample has been analysed in the west?
        It must be a very exciting time for chemical scientists ,it seems to be somewhat of a legendary substance

        • Francesca

          So Dan
          for you as the house expert
          it has been said that with the co-operation of the OPCW, Iran , in late 2016 managed to synthesise some types of Novichok

          This is very much your field
          Do you have any refutation of the above article?
          Which seems to point to the possibility of states other than Russia having the ability to produce novichoks

          So has the OPCW included Novichoks on its data base or not?
          It’s all very confusing
          Presumably, as you are academically and professionally involved in this field, you would have known of the Iranian efforts?
          Why no mention?

          • Francesca

            And incidentally, the links you provided , while very interesting, are rather old.
            I’m really rather puzzled you didn’t include the more up to date Iranian efforts
            If you don’t answer, I guess silence can be as illuminating as anything

          • DDTea

            I’ll paraphrase something I’ve written elsewhere:

            There is an enormous difference between synthesizing the agent on an analytical scale (GC/MS and LC/MS/MS require only milligrams of sample) and weaponizing it–especially if it’s a dusty agent, as is now being alleged. Completely different skill sets. In the report by Saeidian and coworkers, [1] the nerve agents were synthesized on a ~50-100 milligram scale or thereabouts, which is not relevant for a chemical attack.

            But there are greater barriers to using these nerve agents than their synthesis. The toxicological profile, physical properties, and spectral characteristics of Mirzayanov’s reported agents are not in the public literature. These would have to be determined experimentally, which is partly the reason for the study by Saeidian. It was not generally known that these are even effective nerve agents (i.e., not environmentally labile, somewhat shelf stable) or their toxic portals of entry. This would also have to be studied–and toxicological studies require skillsets outside of those of a synthetic chemist. Synthesizing the agents on a pilot scale for such studies and performing these tests–safely–would be a major R&D undertaking requiring significant expenditures and capital investment to handle such high potency compounds. Choosing the one fit for the present assassination attempts (given that there are allegedly hundreds of variations) could only stem from such efforts. The investment of resources is comparable to any pharmaceutical development, which is typically estimated in the billions of dollars.

            So the mass spectrometry study performed by a joint Iranian/OPCW research group is by no means a demonstration of an Iranian capacity to use Novichok agents as a weapon. Not by a long shot.

            [1] Hosseini et. al. “Fragmentation pathways and structural characterization of organophosphorus compounds related to the Chemical Weapons Convention by electron ionization and electrospray ionization tandem mass spectrometry.” Rapid Communications in Mass Spectrometry, 2016, 30, pp. 2585.

  6. Francesca

    Nobody is suggesting that Iran would have any motive to assassinate Skripal
    But it rather defeats the idea that only the Soviets were able to synthesise it
    And there is no literature on methods of weaponisation , even Mirzayanov said he wouldn’t have a clue
    This apparently is the only recorded case(as far as allegations go)that it has been weaponised.And so far there is no evidence whatsoever , but much speculation , on how the agent was delivered.As you say, the program to weaponise it would take billions,and a very big R&D effort, facilities and would be rather hard to keep quiet, or away from the experienced eyes of the OPCW who were in Russia for some years verifying the destruction of all Russia’s chemical weapons
    I’m not interested in all the chemical gobbledygook, I’m interested in what we know of the Novichok’s use and previous history
    What was the method of weaponisation, what was the vehicle, that apparently was so successful that a WMD was able to focus on only 3 victims?and cause no damage to bystanders
    So far this has not been discovered

    I have no doubt that if Novichoks have been used for the first time it would be utterly irresponsible for the British authorities not to make available the medical notes of the 3 victims, and there are ONLY 3 victims of “poisoning ” according to the Salisbury hospital ED medical consultant in a little remarked upon letter to the London Times.
    Thank you for answering ddt, but I would prefer Dan to answer my specific questions pertaining to him


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