Phosphonothioic acid, methyl-, S-(2-(bis(1-methylethyl)amino)ethyl) O-ethyl ester

TIH (Toxic Inhalation Hazard) - Term used to describe gases and volatile liquids that are toxic when inhaled. Some are TIH materials themselves, e.g., chlorine, and some release TIH gases when spilled in water, e.g., chlorosilanes. [ERG 2016].

Environment: Large scale procedure (greater than 50 g) -- use both calcium hypochlorite (HTH) and NaOH...The small-scale decontamination procedure uses sufficient alcoholic HTH to oxidize. If alcoholic HTH mixture is not available, then use following in the order of preference: Decontaminating Agent (DS2), Supertropical Bleach Slurry (STB), and Sodium Hypochlorite.

Cover with vermiculite, diatomaceous earth, clay or fine sand. An alcoholic HTH mixture is prepared by adding 100 milliliters of denatured ethanol to a 900-milliliter slurry of 10% HTH in water just prior to use since the HTH can react with the ethanol. Mix 14 g of alcoholic HTH solution for each 1 g of VX and agitate as added for a minimum of 1 hr. The mixture will give off heat and gas which should be routed through a decontaminate filled scrubber before release through filtration systems. After the 1 hr minimum agitation, 10% sodium hydroxide is added to produce a pH of 12.5 which is maintained for not less than 24 hr. Hold the material at a pH 10 - 12 for 90 days. Scoop decontaminated material and place in approved container. After sealing, decontaminate the exterior and label. All leaking containers will be over packed with sorbent (e.g. vermiculite) placed between the interior and exterior containers. Label and dispose according to regulations. Conduct general area monitoring.

Vaporized hydrogen peroxide (VHP) has proven efficacy for biological decontamination and is a common gaseous sterilant widely used by industry. Regarding chemical warfare agent decontamination, VHP is also effective against HD and VX, but not GD. Simple addition of ammonia gas to VHP affords reactivity toward GD, while maintaining efficacy for HD (and bioagents) and further enhancing efficacy for VX. Thus, modified VHP is a broad-spectrum CB decontaminant suitable for fumigant-type decontamination scenarios, i.e., building, aircraft, and vehicle interiors and sensitive equipment. ...Commercial ammonia-containing cleaners are also shown to be effective surface decontaminants for GD, but not for VX or HD.

Principles and methods for destruction of chemical weapons: ... "Destruction of chemical weapons" means a process by which chemicals are converted in an essentially irreversible way to a form unsuitable for production of chemical weapons, and which in an irreversible manner renders munitions and other devices unusable as such. ... Each /nation/ shall determine how it shall destroy chemical weapons, except that the following processes may not be used: dumping in any body of water, land burial or open-pit burning. It shall destroy chemical weapons only at specifically designated and appropriately designed and equipped facilities. ... Each /nation/ shall ensure that its chemical weapons destruction facilities are constructed and operated in a manner to ensure the destruction of the chemical weapons; and that the destruction process can be verified under the provisions of this Convention. /Chemical warfare agents/

The US Army is pilot testing the neutralization of VX nerve agent stockpiled at Newport, Indiana using caustic hydrolysis in a Sequencing Batch Reactor (SBR). The resulting hydrolysate was tested at the bench-scale for treatment with activated sludge biodegradation in two distinct studies, one in the SBR and another, in the PACT process. The feed to both biological systems was pretreated to enhance the biodegradability of the hydrolysis products. Both biodegradation studies demonstrated that the hydrolysate could easily meet the Chemical Weapons Convention treaty and US environmental regulations following pretreatment.

The Newport Chemical Agent Disposal Facility (NECDF) was designed and constructed to safely neutralize more than 1,000 tons of liquid nerve agent VX currently stockpiled at the Newport Chemical Depot in Indiana. The NECDF uses a chemical neutralization process called caustic hydrolysis to eliminate the lethal toxicity of the nerve agent. ... In a carefully controlled, monitored environment, NECDF operators neutralize the VX by adding the agent to a solution of water and sodium hydroxide. The mixture is heated to accelerate the chemical reaction that breaks down the VX. The resulting byproduct of the neutralization process is a caustic wastewater also called caustic hydrolysate. After the reaction is complete, excess sodium hydroxide is maintained in the caustic hydrolysate to create a "reactive matrix." The excess sodium hydroxide ensures that agent cannot be present or form over time. Before the hydrolysate is removed from the NECDF, lab analysis must confirm the following stringent criteria are met: (1) Hydrolysate is non-detect for VX, with a Method Detection Limit (MDL) of less than or equal to 20 parts per billion (ppb); and (2) Hydrolysate contains less than 1 part per million (ppm) of EA2192, a byproduct of the neutralization process.

A Preliminary Assessment of Health Impacts (PAHI) study was conducted to look at potential human and environmental health impacts due to the air and water emissions generated from the proposed Newport Chemical Agent Disposal Facility (NECDF) in Newport, Indiana. As an alternative to incineration, the NECDF will use a neutralization-based treatment process followed by supercritical water oxidation to destroy the VX nerve agent stored in ton containers at the Newport Chemical Depot. There is no regulatory guidance on conducting an assessment of health impacts for this type of facility. Therefore, The U.S. Army Center for Health Promotion and Preventive Medicine (USACHPPM) designed a Preliminary Assessment of Health Impacts study based on bench-scale data and best engineering estimates that conservatively evaluate possible health effects from the projected air and water emissions. The air portion of the Preliminary Assessment of Health Impacts focused primarily on estimating carcinogenic risks and noncarcinogenic hazards from direct and indirect exposures to the subsistence farmer, subsistence fisher, adult resident, and child resident. The water portion of the Preliminary Assessment of Health Impacts evaluated potential human and environmental impacts using two different procedures individual compound analysis and whole effluent toxicity analysis. The individual compounds analysis compared constituent concentrations in the water emission to Indiana State Water Quality Standards and U.S. Environmental Protection Agency Ambient Water Quality Criteria to evaluate the potential health impacts to human, terrestrial, and aquatic life. The whole effluent toxicity tests were conducted on mammalian (mouse, rat, and rabbit) and aquatic (water flea, algae, and minnows) species to test for potential additive, synergistic, and antagonistic effects. The results of the air and water portion of the study showed that the operation of NECDF would be safe to exposed human and environmental receptors. A Final Assessment of Health Impacts (FAHI) will also be conducted by USACHPPM, after NECDF is constructed and before full-scale operations, to validate the results of the Preliminary Assessment of Health Impacts.

Current recommendations for decontamination of civilians exposed to chemicals as a result of release of such substances by terrorists. ... decontamination of the entire body - not just, for example, the hands and face, should be undertaken. All clothing should be removed and placed in sealed polythene bags. Jewelry, watches, money and other personal possessions should be collected and placed in labeled polythene bags. Two approaches to decontamination are feasible: the "bucket and sponge" method taking one patient at a time, or the mass decontamination approach with attendants supervising the passage of a queue of people through some communal shower unit. Patients who have been injured or are unable to help themselves should be decontaminated by trained attendants using a system in which a stretcher is placed on a table equipped with rollers that allows transfer of the decontaminated patient to a clean stretcher, and ambulance and to hospital. Some authorities have argued for the addition of liquid soap to the water used in automated decontamination units. This will speed the process of material but the interaction of water and soap leading to foaming when passed through a jet should be considered. Whatever means of decontamination are used it should be thorough. This means that each patient will need some minutes of attention: up to 15 or so minutes may be needed to deal with an incapacitated patient. Whatever system is used, plans for dealing with waste water and any decontaminants used should be devised and practiced in advance of an incident occurring. Waste water may be collected inside an area protected by inflatable "bunds". ...If waste water is to be allowed to run into drains, the local water company should be informed. ...Suitable towels and clothing must be provided, modesty should be preserved and consideration given to how people are to make their way home. /Chemical warfare agents/

Decontaminating "non-ambulatory" patients is very staff-intensive and time-consuming but should generally be the primary focus of health effort at the scene. ... Dealing with those who are "ambulatory" is a quicker process as they should normally be able to carry out their own decontamination under supervision ... /Chemical warfare agents/

Identifying the chemical(s) involved and measuring its concentration would obviously be helpful... but may not prove possible until more specialist support arrives and so responders are likely to be reliant on environmental indicators and/or the signs and symptoms displayed by victims. In practice, information gathered during clinical examination may be most useful. /Chemical warfare agents/

Any chemical release will have its maximum harmful effect against unprotected individuals, so those who self-evacuate and the rapidly rescued will generally have the best survival and recovery prospects. Planners and incident commanders should bear in mind that by the time rescue efforts are mounted survivors are generally unlikely to be found in environments or circumstances that demand the wearing of self-contained respiratory protection. Health plans should also recognize that the level of meaningful assessment or treatment that can be carried out in the ... hot zone... will be very limited. ... Rapid rescue from the hot zone represents the most practical and effective operational approach and in most major releases the most effective health response is likely to be focused in the more lightly contaminated ("warm") and uncontaminated ("cold") zones. There - and at receiving hospitals - the main emphasis should be on providing the type of respiratory and physical protection for staff so that secondary contamination is prevented. Unprotected staff should not come into contact with undecontaminated patients. /Chemical warfare agents/

0.000016 [ppm]

0.00027 [ppm]

0.00091 [ppm]

For information on chemical warfare nerve agents see the ERG Criminal or Terrorist Use of CBR Agents. (ERG, 2024)

Recommendations for Personal Protective Equipment /PPE/ should be based on a site-based job hazard analysis of possible hazards including skin contact, air concentrations, heat stress, etc. All PPE should be used with appropriate additional administrative controls including medical surveillance, employee training, respirator fit-testing, and decontamination procedures to limit the potential for unforeseen adverse effects. /Nerve Agents/

Personal Protective Requirements: "G" series Nerve Agents pose both a severe respiratory and severe contact hazard. Wear appropriate fully encapsulating protective gear with positive pressure self contained breathing apparatus (SCBA). Structural firefighters' protective clothing is recommended for fire situations only; it is not effective in spill or release events. Thickened agents pose a less significant vapor hazard but a much more significant contact hazard. /"G" Series Nerve Agents/

Hold breath until respiratory protective mask is donned. Fire-Fighting personnel should wear full protective clothing and respiratory protection during fire fighting and rescue. Pressure demand, self-contained breathing apparatus (SCBA) (SCBA CBRN, if available) is recommended in response to non-routine emergency situations. CBRN, Full Facepiece APR (when available) is recommended in non-routine, emergency situation environments less than IDLH but above REL or PEL levels.

Acute Exposure Guideline Levels (AEGLs): Agent VX

/The Chemical Weapons Convention (CWC) is an international treaty which bans the development, production, stockpiling, and transfer or use of chemical weapons. The Convention mandates the destruction and prohibition of chemical weapons and related facilities and provides for restrictions on international trade in toxic chemicals and precursors./ The Convention's monitoring and verification measures involve submission of declarations regarding ... /Schedule 1, 2, and 3 chemicals/ and inspections by the Organization for the Prohibition of Chemical Weapons of the facilities where these chemicals are produced. ... Schedule 1 lists chemicals considered to pose a high risk to the object and purpose of the Convention by virtue of their high potential for use in activities prohibited by the CWC. These chemicals have little or no use for peaceful purposes in commercial or industrial trade. ... Schedule1 also lists precursor chemicals that may be used in the final single technological stage of production of any of the toxic chemicals listed in the schedule (2). O-Ethyl S-(2-diisopropylaminoethyl)methylphosphonothioate is listed in the CWC Annex on Chemicals under Schedule 1 (1).

/A National Research Council Subcommittee recommended to the military/ the following guidelines for the organophosphorus nerve agents: GA, 22.5 ug/L and 70.0 ug/L; GB, 4.6 and 13.8 ug/L; GD, 2.0 and 6.0 ug/L; and VX, 2.5 and 7.5 ug/L assuming a water consumption of 15 and 5 L/day, respectively.

Summary of CDC and U.S. Army Airborne Exposure Limits: IDLH 0.003 mg/cu m; STEL 0.00001(1E-5) mg/cu m; Worker Population Limit (WPL) 0.000001 (1E-6); General Population Limit 0.0000006 (6E-7); Percutaneous Vapor Toxicity (Calculated Minimal Effect Values for 2 hour Exposure Period) 0.03 mg/cu m

Two guinea pig models were used to study the anticonvulsant potency of diazepam, midazolam, and scopolamine against seizures induced by the nerve agents tabun, sarin, soman, cyclosarin, O-ethyl S-(2-(diisopropylamino)ethyl)methylphosphonothioate (VX), and O-isobutyl S-(2-diethylamino)ethyl)-methyl phosphonothioate (VR). Animals instrumented for electroencephalogram recording were pretreated with pyridostigmine bromide (0.026 mg/kg im) 30 min before challenge with 2 x LD50 (s.c.) of a nerve agent. In model A, atropine sulfate (2.0 mg/kg im) and pyridine-2-aldoxime methylchloride (2-PAM; 25.0 mg/kg im) were given 1 min after nerve agent challenge, and the tested anticonvulsant was given (im) 5 min after seizure onset. In model B, a lower dose of atropine sulfate (0.1 mg/kg im) was given along with 2-PAM 1 min after nerve agent challenge, and the anticonvulsant was given at seizure onset. With the lower dose of atropine, seizure occurrence increased to virtually 100% for all agents; the time to seizure onset decreased for sarin, cyclosarin, and VX; the signs of nerve agent intoxication were more severe; and coma resulted frequently with cyclosarin. The anticonvulsant ED50 doses for scopolamine or diazepam were, in general, not different between the two models, whereas the anticonvulsant ED50 values of midazolam increased 3- to 17-fold with the lower atropine dose. Seizure termination times were not systematically affected by the different doses of atropine. The order of anticonvulsant effectiveness within each model was scopolamine > or = midazolam > diazepam. The findings indicate that the dose of atropine given as antidotal therapy can significantly influence measures of nerve agent toxicity and responsiveness to anticonvulsant therapy.

Currently fielded treatments for nerve agent intoxication promote survival, but do not afford complete protection against either nerve agent-induced motor and cognitive deficits or neuronal pathology. The use of human plasma-derived butyrylcholinesterase (HuBuChE) to neutralize the toxic effects of nerve agents in vivo has been shown to both aid survival and protect against decreased cognitive function after nerve agent exposure. Recently, a commercially produced recombinant form of human butyrylcholinesterase (r-HuBuChE ...) expressed in the milk of transgenic goats has become available. This material is biochemically similar to plasma-derived HuBuChE in in vitro assays. The pharmacokinetic characteristics of a polyethylene glycol coated (pegylated) form of r-HuBuChE were determined in guinea pigs; the enzyme was rapidly bioavailable with a half-life (t1/2) and pharmacokinetic profile that resembled that of plasma-derived huBuChE. Guinea pigs were injected with 140 mg/kg (im) of pegylated r-HuBuChE 18 hr prior to exposure (sc) to 5.5xLD50 VX or soman. VX and soman were administered in a series of three injections of 1.5xLD50, 2.0xLD50, and 2.0xLD50, respectively, with injections separated by 2 hr. Pretreatment with pegylated r-HuBuChE provided 100% survival against multiple lethal doses of VX and soman. Guinea pigs displayed no signs of nerve agent toxicity following exposure. Assessments of motor activity, coordination, and acquisition of spatial memory were performed for 2 weeks following nerve agent exposure. There were no measurable decreases in motor or cognitive function during this period. In contrast, animals receiving 1.5xLD50 challenges of soman or VX and treated with standard atropine, 2-PAM, and diazepam therapy showed 50 and 100% survival, respectively, but exhibited marked decrements in motor function and, in the case of GD, impaired spatial memory acquisition. The advances in this field have resulted in the decision to select both the plasma-derived and the recombinant form of BuChE for advanced development and transition to clinical trials. ...

Organophosphorus compounds such as nerve agents inhibit, practically irreversibly, cholinesterases by their phosphorylation in the active site of these enzymes. Current antidotal treatment used in the case of acute nerve agent intoxications consists of combined administration of anticholinergic drug (usually atropine) and acetylcholinesterase (AChE, EC 3.1.1.7) reactivator (HI-6, obidoxime, pralidoxime), which from a chemical view is a derivative from the group of pyridinium or bispyridinium aldoximes (commonly called "oxime"). Oximes counteract acetylcholine increase, resulting from AChE inhibition. In the human body environment these compounds are powerful nucleophiles and are able to break down the bond between AChE and nerve agent molecule. This process leads to renewal of enzyme functionality -- to its reactivation. The usefulness of oxime in the reactivation process depends on its chemical structure and on the nerve agent whereby AChE is inhibited. Due to this fact, selection of suitable reactivator in the treatment of intoxications is very important. This work compared differences in the in vitro inhibition potency of VX and Russian VX on rat, pig and human brain, and subsequently we have tested reactivation of rat brain cholinesterase inhibited by these agents using oxime HI-6, obidoxime, pralidoxime, trimedoxime and methoxime. The results showed that no major differences in the reactivation process of both VX and Russian VX-inhibited cholinesterase. The similarity in reactivation was caused by analogous chemical structure of either nerve agent; and that oxime HI-6 seems to be the most effective reactivator tested, which confirms that HI-6 is currently the most potent reactivator of AChE inhibited by nerve agents...

... The present work was designed to assess the ability of butyrylcholinesterase, purified from human serum (HuBChE), to prevent the toxicity induced by soman and VX in rhesus monkeys. The consistency of the data across species was then evaluated as the basis for the extrapolation of the data to humans. The average mean residence time of the enzyme in the circulation of monkeys following an intravenous loading was 34 hr. High bioavailability of HuBChE in blood (>80%) was demonstrated after intramuscular injection. A molar ratio of HuBChE:OP approximately 1.2 protected against an i.v. bolus injection of 2.1 x LD50 VX, while a ratio of 0.62 was sufficient to protect monkeys against an i.v. dose of 3.3 x LD50 of soman, with no additional postexposure therapy. A remarkable protection was also seen against soman-induced behavioral deficits detected in the performance of a spatial discrimination task. The consistency of the results across several species offers a reliable prediction of both the stoichiometry of the scavenging and the extent of prophylaxis with HuBChE against nerve agent toxicity in humans.

For more Interactions (Complete) data for VX (9 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 187(SRC), determined from a structure estimation method(2), indicates that VX is expected to have moderate mobility in soil(SRC). The pKa of VX is 9.12(3), indicating that this compound will partially exist in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Tight adsorption to dry soil(5) and rapid adsorption to sand(6) have been observed. Simulated rainfall events were shown to desorb the VX from dry soil resulting in volatilization to the atmosphere(6). Volatilization of VX from moist soil surfaces where VX is dissolved in water may not be an important fate process(SRC) given an estimated Henry's Law constant of 1.0X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 8.78X10-4 mm Hg(7), and water solubility, 3.0X10+4 mg/L(8). VX does volatilize from dry surfaces, however, evaporation of VX from solid surfaces is a relatively slow process compared to other nerve agents such as GD or HD(6); the time for complete evaporation of VX was 6 days for a 0.5 micro-liter drop at 30 °C on a glass surface(6). Laboratory and field studies indicate the disappearance of nerve agents from soil results from a combination of processes including evaporation, hydrolysis and microbial degradation(9). VX is susceptible to aqueous hydrolysis with rates varying with pH, temperature, presence of natural species (such as fulvic acid), and other factors(9,10); therefore, hydrolysis in moist soil is expected to be an important fate process(SRC). Field and closed-container studies indicate that approximately 90% of VX is lost from soil in 15 days(9); however, hydrolysis rates can vary markedly depending on conditions and requires further study(10).

TERRESTRIAL FATE: VX may be deposited on land as a result of a spill or as a result of its use in chemical warfare. When disseminated over bare or vegetated terrain, water may be quite limited and may be largely derived from the atmosphere; hydrolysis would therefore depend on the humidity and the diffusion of water vapor into an agent droplet. Deposition in cold regions presents a special problem since degradative processes are much slower and evaporative losses less. When disseminated over snow and ice, VX should spread on the surface. If freezing takes place after the agent is disseminated, the agent will be distributed in ice, segregated into concentrated pockets, or concentrated along grain boundaries depending upon the rate of cooling. The distribution and concentration of the agent may affect the hydrolysis rate(1).

TERRESTRIAL FATE: VX is moderately persistent on bare ground, remaining at high concentrations for about 2-6 days. The persistence of VX in soil is a function of temperature, organic carbon content of the soil, and possibly moisture content of the soil. In oven-dried soil or in soil where the temperature is below freezing, degradation is very slow(1). Little agent is lost through evaporation probably due to its low vapor pressure and Henry's Law constant. On vegetation, it evaporates in 24 to 48 hr(2). When VX was applied to humic sand, humic loam, and clayey peat in laboratory studies, it was rapidly hydrolyzed into ethyl hydrogen methylphosphonate that was slowly converted to methylphosphonic acid(3). After 1 day, about 3% of the applied VX remained in the humic loam and clayey peat and 20% remained in the humic sand. The remainder disappeared at a much slower rate and after 3 weeks only 0.1% was detected. In addition to degradation, it is thought that chemisorption may have contributed to the rapid initial disappearance of VX in the humic loam and clayey peat(SRC). VX was observed to have a high affinity for activated charcoal, moderate affinity for montmorillonite /(OH)4Si8Al4O20.nH2O/, and little affinity for goethite /hydrated iron xoide: FeO(OH)/(4). The affinity for goethite increased with the addition of fulvic acid, but did not increase its affinity to montmorillonite(4). Although dry goethite degraded VX in methylene chloride, wet goethite was observed to block electron interactions and reduce degradation in soil(4).

Effects from skin exposure to liquid nerve agent may not develop for up to 18 hours following exposure. Patients who have inhalation exposure and who complain of chest pain, chest tightness, or cough should be observed and examined periodically for 6 to 12 hours to detect delayed-onset bronchitis, pneumonia, pulmonary edema, or respiratory failure. Patients who have severe exposure should be evaluated for persistent CNS sequelae. Patients should be advised to avoid organophosphate insecticide exposure until sequential RBC cholinesterase activity (measured at weekly to monthly intervals) has stabilized in the normal range, a process that may take 3 to 4 months after severe poisoning.

Routine laboratory studies for all admitted patients include CBC, glucose, and serum electrolyte determinations. Chest X-ray and pulse oximetry (or ABG measurements) are recommended for severe exposures. Symptomatic and asymptomatic patients suspected of significant exposure should have determinations of red blood cell (RBC) cholinesterase activity, the most useful test for nerve agent poisoning. Severe symptoms of toxicity are usually present when more than 70% of RBC cholinesterase is inhibited. However, there is no correlation between cholinesterase activity and severity of topical signs and symptoms (e.g., miosis, rhinorrhea, dyspnea). If this test is not available, plasma cholinesterase can be measured.

Laboratory criteria for diagnosis. Biologic: A case in which nerve agents in urine are detected, as determined by CDC or one of five LRN laboratories that have this capacity. Decreased plasma or red blood cell cholinesterase levels based on a specific commercial laboratory reference range might indicate a nerve agent or organophosphate exposure; however, the normal range levels for cholinesterase are wide, which makes interpretation of levels difficult without a baseline measurement or repeat measurements over time. -OR - Environmental: Detection of organophosphate pesticides in environmental samples, as determined by FDA. However, a confirmation test for nerve agents in environmental samples is not available. /Nerve Agents/

Using a structure estimation method based on molecular connectivity indices(1), the Koc of VX can be estimated to be 187(SRC). According to a classification scheme(2), this estimated Koc value suggests that VX is expected to have moderate mobility in soil. The pKa of VX is 9.12(3) indicating that this compound will partially exist in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Low concentrations of VX are tightly bound to dry Dugway soil(5). VX deposited on sand undergoes rapid adsorption followed by slow evaporation(6); adsorption to the sand can remain, but simulated rainfall can desorb the VX resulting in vapor-phase release(6). No VX sorption was observed with kaolinite, but VX sorption by montmorillonite was rapid with the predominant mechanism consistent with an ion exchange(7); VX also interacted with two soils resulting in sorption(7). A study compared the adsorption affinity of VX for several different surfaces similar to those found in the environment; activated charcoal, montmorillonite, and goethite(8). The activated charcoal had the greatest affinity, montmorillonite had a moderate affinity, and goethite had little affinity(8). Goethite's affinity increased with the addition of fulvic acid, but montmorillonite's did not(8). Although goethite degraded VX dissolved in methylene chloride, wet goethite was observed to block electron interactions and reduce degradation in soil(8).

/HUMAN EXPOSURE STUDIES/ Eight volunteers from the Porton medical staff took part in a study involving the inhalation of VX vapor in 1961 and 1962. ... In total the study featured 54 exposures. No man was exposed either for the first time or subsequently unless his ChE was within normal limits. Only the head and neck were exposed. ... At the end of the exposure, no washing of the face or any form of decontamination was allowed for 8 hours. 19 exposures involved men with no respiratory protection. Fifteen of the exposures lasted either 3 minutes or 1.5 minutes, at 0.6 - 3.6 mg.min/cu m. The remaining 4 exposures lasted for 6 minutes or 7 minutes, at 4.8 - 6.4 mg.min/cu m. The following effects were noted: the maximum ChE depression observed was 70% in RBC ChE but plasma ChE was very much less depressed than RBC ChE; miosis developed 1-3 hours after exposure and usually passed off 36 hours later. The remaining 35 exposures involved the same men being exposed but with respiratory protection: a mouthpiece and a clip over the nose. Twenty five of the exposures lasted between 1.5 minutes and 4 minutes (exposure levels of 0.7 - 20 mg.min/cu m). The remainder were longer (9 - 24 minutes, 7.7 - 25.6 mg.min/cu m). In practical terms, men undergoing these exposures did not breathe in VX vapor, but the following results were recorded: no symptoms were observed during the exposure, although nearly all subjects developed miosis 30 minutes after exposure; ChE was depressed, in two of the exposures by more than 50%. The second result was quite startling: it suggested that VX vapor was absorbed quite rapidly through the skin of the face and neck, so that even with protection a man would be vulnerable to VX vapor. In reviewing this result, the BC noted that VX vapor absorbed through the skin could be as great a danger to a masked man as GB was to an unmasked man.

/HUMAN EXPOSURE STUDIES/ Service volunteers took part in three studies of the eye effects of VX vapor in 1968 and 1969... . The first study ... investigated the effect of speed. Twenty five volunteers took part. Their eyes were exposed to different concentrations of VX vapor, 0.025 - 0.92 mg/cu m, passed over the eyes at different speeds, 0.01 - 2.2 m/s. As vapor at higher wind speeds was expected to cause more miosis, lower doses were used. In all, 25 volunteers underwent 101 exposures, counting each eye as one exposure. The main conclusions of the study were: at low wind speeds (0.01 m/s), 90% miosis resulted from VX vapor at 7 mg.min/cu m; at higher wind speeds (2.2 m/s), 90% miosis resulted from VX vapor at only 0.09 mg.min/cu m; VX vapor exposure levels to induce 90% miosis were smaller than those of GB. The second study explored the effect of miosis on the ability to see in dim light... . Here, 7 volunteers had one eye exposed to VX vapor, while the other was not exposed. The degree of miosis induced was always greater than 50%. The study showed (as for GB miosis) that mild miosis (70% or less) had practically no effect on visual acuity in dim light but miosis of 90% or more constituted a handicap. The third and final human study with VX considered the effect of miosis on the eye's ability to recover to seeing in dim light after exposure to a bright light. ... In this study 5 volunteers had their eyes exposed to VX vapor. Two were rendered miotic in both eyes, three in one eye only. Some were exposed to VX vapor through goggles. In all cases, the degree of miosis induced was less than 50%.

An estimated BCF of 11 was calculated in fish for VX(SRC), using a log Kow of 2.09(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for VX is estimated as 1.08X10-8 atm-cu m/mole(SRC) derived from its vapor pressure, 8.78E-4 mm Hg at 25 °C(1), and water solubility, 3.0X10+4 mg/L(2). This Henry's Law constant indicates that VX is expected to be essentially nonvolatile from water surfaces(3). VX's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may not be an important fate process(SRC). VX does volatilize from dry surfaces, however, evaporation of VX from solid surfaces is a relatively slow process compared to other nerve agents such as GD or HD(4); the time for complete evaporation of VX was 6 days for a 0.5 micro-liter drop at 30 °C on a glass surface(4); evaporation from concrete is slower due to surface adsorption(4); evaporation rates from soil were not measured(4). When deposited on sand, after rapid adsorption, VX evaporated slowly for an extended period of time(4); addition of water in the form of simulated rain can release adsorded VX in vapor-form(4).

Because chemical agents are dispersed in the form of droplets, it is important to consider the factors affecting the persistence of these droplets. Persistence will be a function of drop size, temperature, and air velocity(1). A linear equation has been developed relating the log of the time for 90% of a droplet to evaporate and the log of the volatility(1). The estimated volatilization time for 1-mm VX drops on a hard surface with a 2 m/sec wind is (time (temperature)): 44.6 days (10 °C), 193.0 days (0 °C), 936 days (-10 °C), 5150 days (-20 °C), 89 yr (-30 °C), 666 yr (-40 °C)(1). Extrapolated vapor pressure data were used below -20 °C. For other drop sizes, the volatilization time is found by multiplying the above volatilization times by the drop diameter in millimeters. For other wind velocities, the correction factor (u/2)-0.798 is applied, where u is the wind speed in m/sec(SRC). Another investigator found that volatilization of droplets at different temperatures and wind speeds can be calculated by multiplying the volatilization time at a reference temperature and wind speed by the ratio of the vapor pressure at the new temperature and cube root of the new wind speed to that of the reference temperature and wind speed(2). Humidity may affect evaporation since absorption of atmospheric moisture causes dilution and concomitantly an increase in the drop size(SRC).

/LABORATORY ANIMALS: Acute Exposure/ The short-term toxicity of VX to Sprague-Dawley rats was investigated ... . In one series of tests, a single sc injection of 1 ug VX/kg resulted in a 50% inhibition of RBC-AChE relative to controls and a dose of 4 ug/kg resulted in a 87% inhibition relative to controls. In a second test series, male rats were dosed with 4 ug VX/kg by different exposure routes and RBC-AChE levels relative to controls were determined at 3 hr and at 24 hr. High variability in response was seen in animals dosed by intratracheal instillation, intragastric lavage, and ip injection. RBC-AChE levels were reduced a similar amount for sc injections (13 +/- 7% of control values at 3 hr and 21% at 24 hr) and iv injections (14 +/- 0.07% of control values at 3 hr and 20% at 24 hr). In another pilot study, male and female rats (8 - 10 weeks old) were injected sc with 0, 0.25, 0.63, 1.56, 3.91, 9.77, or 14.65 ug VX/kg/day, 5 days/week for 14 days. Each dose group consisted of eight males and eight females except for the high-dose group which had two males and two females. All the animals in the two highest dose groups died as a result of the exposures, but none of the animals in the ... other dose groups died as a result of the exposures. Of the remaining animals, one-half was sacrificed at 7 days and the other half at 14 days. RBC-AChE activity levels were depressed in all dose groups in a dose- dependent manner.

/LABORATORY ANIMALS: Acute Exposure/ ... the purpose of this study was to examine the clinical manifestations of VX intoxication in the domestic white pig following a 2 x LD50 (120 ug/kg) percutaneous challenge. There was a consistent onset of signs (where present) in each animal: mastication was followed by miosis, salivation, fasciculations and apnea. While ChE activity did not correlate with the onset of signs, there was a qualitative relationship in that mastication preceded substantial ChE inhibition, miosis lagged behind the linear decrease in acetylcholinesterase (AChE) activity and fasciculations and apnea occurred after maximum ChE inhibition had been attained (5-10% of normal). These observations may be of use for the triage of patients exposed to VX. In comparison with similar studies with GD, VX did not affect glucose utilization. However, VX was similar to GD in that it caused a mild hyperkalemia and hyperphosphatemia, although the significance of this observation was not clear. There was substantial lateral diffusion of the initial droplet of VX over the application site, indicating that, when decontaminating exposed skin, attention should also be directed to areas peripheral to the original site of exposure.

/LABORATORY ANIMALS: Acute Exposure/ ... Guinea pigs... were anesthetized ... and VX was aerosolized using a microcatheter placed 2 cm above the bifurcation of the trachea. Different doses (50.4..., 70.4... , and 90.4 ug/cu m) of VX were administered at 40 pulses/min for 5 min. Dosing of VX was calculated by the volume of aerosol produced per 200 pulses and diluting the agent accordingly. Although the survival rate of animals exposed to different doses of VX was similar to the controls, nearly a 20% weight reduction was observed in exposed animals. After 24 hr of recovery, the animals were euthanized and bronchoalveolar lavage (BAL) was performed with oxygen free saline. BAL was centrifuged and separated into BAL fluid (BALF) and BAL cells (BALC) and analyzed for indication of lung injury. The edema by dry/wet weight ratio of the accessory lobe increased 11% in VX-treated animals. BAL cell number was increased in VX-treated animals compared to controls, independent of dosage. Trypan blue viability assay indicated an increase in BAL cell death in 70.4 ug/cu m and 90.4 ug/cu m VX-exposed animals. Differential cell counting of BALC indicated a decrease in macrophage/monocytes in VX-exposed animals. The total amount of BAL protein increased gradually with the exposed dose of VX and was highest in animals exposed to 90.4 ug/cu m, indicating that this dose of VX caused lung injury that persisted at 24 hr. In addition, histopathology results also suggest that inhalation exposure to VX induces acute lung injury.

Children have several vulnerabilities putting them at increased toxicity from this class of chemical agents. A child's smaller mass alone reduces the dose needed to cause symptoms or lethality. For volatile nerve agents, children are especially at risk for respiratory toxicities due to their anatomic differences compared to adults. Their smaller airways can become compromised by the large amount of secretions and the bronchospasm caused by the agents. Also, a greater dose of nerve agent will be inhaled in children due to their higher respiratory rate and minute volumes. /Nerve Agents/

It has been suggested that in nerve agent poisoning butyrlycholinesterase acts as a "sink" for nerve agents. If that is the case it would be expected that those with low or absent butyrylcholinesterase activity would be more susceptible to nerve agents.

The rate constant for the vapor-phase reaction of VX with photochemically-produced hydroxyl radicals is estimated to be 1.6X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). VX does not absorb UV radiation above 290 nm(2) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC). Sensitized photooxidation may occur and has been suggested as a means of decontaminating VX(3). Hydrolysis can be an important fate process with reported half-lives in water at 25 °C and pH 7 ranging from 17 to 42 days(4,5). Hydrolysis rates vary with pH(4,6); at pH 5, the half-life is on the order of 100 days, whereas at pH 8 the half-life is roughly 9 days(6). Batch hydrolysis experiments demonstrated an increasing hydrolysis rate as pH increased, but also indicated that dissolved aqueous constituents (e.g. fulvic acids, carbonates, clays) can cause major differences in absolute hydrolysis rates(6); for example, addition of natural dissolved material at pH 7 increased the hydrolysis rate by a factor of 2(6). Hydrolysis rates in environmental systems where natural dissolved species are present can depend on pH, species and concentration, and other factors(6).

VX contains an amine group and is a base having a pKa of 9.12 at 25 °C(1). The pKa increases slightly with decreasing temperature; at 55 °C the pKa is 8.45(1). At the pHs in the environment (between pH 5 and 9), VX will range from 100% to 50% protonated. VX undergoes hydrolysis in both acid and basic solutions(2). In both strongly alkaline and solutions with pH<6, hydrolysis results exclusively in the cleavage of the P-S bond with the formation of ethyl methylphosphonic acid and diisopropylaminoethylmercaptan. In the pH range 7-10, the situation is more complex; both cleavage of the O-C and C-S bonds occur at 55 °C. Five reaction products have been identified, namely, S-diisopropylamino-ethylmethylphosphonic acid, bis(diisopropyl-aminoethyl) disulfide, bis(diisopropylaminoethyl) sulfide, ethyl methylphosphothiolic acid, and ethanol. At higher pH's, more of VX is present in the unprotonated state resulting in more mercaptan being formed. This results in an increase in the proportion of disulfide versus sulfide in the product mix(SRC).

In recent work at 21 °C, in which the unbuffered hydrolysis of 0.5% VX was followed with 31P NMR, it was found that the principal product is S-(2-diisopropylamino-ethyl)methylphosphonothioic acid (49.9 mole percent) and ethanol which result from the cleavage of the P-O-C bond(1). This acid is very stable and toxic(1). The other pathways, in order of importance, are the cleavage of the P-S bond (34.2 mole percent) and the cleavage of the S-C bond (9.1 mole percent)(1). The overall half-life is 57.3 hr. Results are consistent with three, parallel, first-order reactions that appear to be independent of pH(1). These results are contrary to earlier results that showed the VX hydrolysis to be pH dependent. Earlier work reported a hydrolytic half-life at 25 °C of 96 days below pH 6 that declined to 19.3 days at pH 7.2 and 2.9 days at pH 9(2-3).

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Phosphonothioic acid, methyl-, s-(2-(bis(1-methylethyl)amino)ethyl) o-ethyl ester is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 100 lbs.

VX

CUM 100g

CUM 100g

Chemical Weapons/Chemical Weapons Precursors chemical material that, if stolen or diverted, can be converted into weapons using simple chemistry, equipment, or techniques.

Chemical warfare;

Chemical warfare agent

O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) ... is an extremely toxic organophosphate nerve agent that differs from other well-known organophosphate nerve agents in that its primary use is as a contact poison rather than as an inhalation hazard.

Synthesis: QL /O-Ethyl, 2-diisopropyl aminoethyl methylphosphonate/ and sulfur

Preparation: R.V. Ley, G.L. Sainsbury, United Kingdom patent 1346409; A.W. Wardrop, C. Stratford United Kingdom patent 1346410 (both 1974 to United Kingdom. Sec. of State for Defence); ... S.R. Eckhaus et al., United States of America patent 3911059 (1975 to US Sec. for Army)

Phosphonothioic acid, P-methyl-, S-[2-[bis(1-methylethyl)amino]ethyl] O-ethyl ester: ACTIVE

VX is listed in the CWC /Chemical Weapons Convention/ Annex on Chemicals under Schedule 1.

/The Chemical Weapons Convention (CWC) is an international treaty which bans the development, production, stockpiling, and transfer or use of chemical weapons. The Convention mandates the destruction and prohibition of chemical weapons and related facilities and provides for restrictions on international trade in toxic chemicals and precursors./ The Convention's monitoring and verification measures involve submission of declarations regarding ... /Schedule 1, 2, and 3 chemicals/ and inspections by the Organization for the Prohibition of Chemical Weapons of the facilities where these chemicals are produced. ... Schedule 1 lists chemicals considered to pose a high risk to the object and purpose of the Convention by virtue of their high potential for use in activities prohibited by the CWC. These chemicals have little or no use for peaceful purposes in commercial or industrial trade. ... Schedule 1 also lists precursor chemicals that may be used in the final single technological stage of production of any of the toxic chemicals listed in the schedule (2). VX is listed in the CWC Annex on Chemicals under Schedule 1 (1).

The V-series weapons, including VX, are the most highly toxic chemical warfare nerve agents. ... The V agents are part of the group of persistent agents, which are nerve agents that can remain on skin, clothes, and other surfaces for long periods of time. ... The V agents are approximately 10-fold more poisonous than sarin (GB).

In the early 1950s, ... O-ethyl- S-[2-(diisopropylamino)ethyl]-methylphosphonothioate, now known as VX, was synthesized in England, again in a search for better insecticides.

For more General Manufacturing Information (Complete) data for VX (7 total), please visit the HSDB record page.