CBRNE - Nerve Agents, Binary - GB2, VX2

Updated: Apr 28, 2015
  • Author: Larissa I Velez-Daubon, MD; Chief Editor: Duane C Caneva, MD, MSc  more...
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Overview

Background

In the 1950s, the US Army began to consider the development of binary nerve agent weapons to provide increased safety during storage and handling. At that time, unitary nerve agent weapons were the only ones in existence. In unitary agents, the chemicals were produced in a plant, loaded into the missile, and stored in a ready-to-use fashion. This method has several drawbacks. Because the munitions are highly toxic, storage, handling, and deployment need to be performed with extreme caution. Unitary weapons therefore pose a considerable risk to the ground crew and others who work with the chemicals. The agents in the active form are also highly corrosive; thus, extended storage times increase the risk of a leak.

The concept of binary weapons began to develop in the 1960s. Binary weapons involve nontoxic precursors that can be loaded in munitions. Once deployed, the precursors mix and develop the nerve agent. Below is a timeline (adapted from Sidell, 1997; Smart, 1996; and Organisation for the Prohibition of Chemical Weapons) that highlights important dates in the development of binary technology:

  • 1960s: The BIGEYE, a 500-lb bomb with binary technology, is developed for the US Navy. Its production was halted in 1990.
  • September 16, 1969: A 155-mm projectile filled with sarin binary reagents is test fired at Dugway Proving Ground.
  • 1976: The US Army standardizes the M687 Binary GB2 155-mm projectile.
  • 1976: The US Congress passes the Department of Defense Appropriation Authorization Act, which restricts the development and production of binary weapons unless the President certifies to the Congress that such production is essential to the national interest.
  • 1985: Public Law 99-145 (US Congress) authorizes production of chemical weapons.
  • 1987: President Reagan certifies to US Congress the need for chemical weapons.
  • December 16, 1987: M687 binary projectile starts production at Pine Bluff.
  • June 1, 1990: The United States and the Soviet Union sign the bilateral chemical weapons destruction agreement.
  • 1991: Iraq declares to the United Nations Special Commission (UNSCOM) a different binary munition concept. The projectiles would contain only 1 canister with a single precursor. Before use, the munition would be opened, and the second precursor would be added. The chemical reaction then starts just prior to the munition release.

A binary projectile contains 2 separate, hermetically sealed, plastic-lined containers fitted, one behind the other, in the body of the projectile. In the sarin (GB) binary weapon, the forward canister contains methylphosphonic difluoride (DF). The rear canister contains an isopropyl alcohol and isopropylamine solution (OPA). Only the forward canister is in the munition prior to use. Before the weapon is fired, the rear canister is added and the fuse is placed. The force of launch causes the canisters to break, which produces GB within the projectile.

Known binary agents include the following:

  • GB binary (sarin, GB2): DF is located in 1 canister, while OPA is in a second canister. The isopropyl amine binds to the hydrogen fluoride generated during the chemical reaction. After deployment of the weapon, the 2 canisters rupture and the chemical mixture produces GB.
  • GD binary (soman, GD2): DF is located in 1 canister, while a mixture of pinacolyl alcohol and an amine is in a second canister. After deployment of the weapon, the 2 canisters rupture and the chemical mixture produces GD.
  • VX binary (VX2): O-Ethyl O-2-diisopropylaminoethyl methylphosphonite (QL) is in 1 canister. The other canister contains elemental sulfur. When the weapon is fired, the canisters rupture and the chemical mixture produces VX.
  • Novichok agent ("Newcomer"): a series of nerve agents developed by the Soviet Union in the 1980s and 1990s, all in the "third generation nerve agent" category. Some of these agents (Novichok-5, Novichok-7) are binary agents.

The final product of the weapon is of the same chemical structure as the original nerve agent. The term binary refers only to the storage and deployment method used, not to the chemical structure of the substance. This article discusses management of chemical nerve agents in general; the reader can also refer to CBRNE - Nerve Agents, G-series - Tabun, Sarin, Soman and CBRNE - Nerve Agents, V-series - Ve, Vg, Vm, Vx for more detailed information on each particular agent.

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Pathophysiology

Nerve agents comprise various compounds that have the capacity to inactivate the enzyme acetylcholinesterase (AChE). They are generally divided into 2 families, the G agents and the V agents (VX is the prototype of V agents). The Germans developed the G agents (ie, tabun [GA], sarin [GB], soman [GD]) during World War II. The G agents are highly volatile liquids that pose mainly an inhalation hazard. The V agents were developed later in the United Kingdom. They are approximately 10 times more toxic than GB. The V agents are less volatile and have an oily consistency; thus, they mainly pose a contact hazard. They are considered "persistent agents," which means that they can remain viable on surfaces for long periods of time.

Nerve agents bind to AChE much more potently than organophosphate and carbamate insecticides do. AChE is the enzyme that mediates the degradation of acetylcholine (ACh). ACh is an important neurotransmitter of the peripheral and central nervous systems. Acetylcholine activates 2 types of receptors, muscarinic and nicotinic. Nicotinic ACh receptors are found at the skeletal muscle and at the autonomic ganglia. The muscarinic receptors are found mainly in the postganglionic parasympathetic fibers and the brain. Therefore, nerve agent toxicity is manifested as excessive cholinergic transmission at both types of receptor sites.

ACh is released when an electrical impulse reaches the presynaptic neuron. The neurotransmitter travels across the synaptic cleft and reaches the postsynaptic membrane. There, it binds to its receptor (muscarinic or nicotinic). This interaction leads to activation of the ACh receptor and signal transmission in the postsynaptic side of the cleft. Normally, after this interaction between ACh and its receptor, ACh is rapidly degraded (hydrolyzed) into choline and acetic acid by AChE. This renders the ACh receptor active again. Choline undergoes reuptake into the presynaptic cell and is used to regenerate ACh.

Nerve agents act by inhibiting the hydrolysis of ACh by AChE. They bind to the active site of AChE, rendering it incapable of deactivating ACh. Any ACh that is not hydrolyzed can continue to interact with the postsynaptic receptor, which results in persistent and uncontrolled stimulation of that receptor. After persistent activation of the receptor, fatigue results. This is the same principle exhibited by the depolarizing neuromuscular blocker succinylcholine. The clinical effects of nerve agents are the result of this persistent stimulation and subsequent fatigue at the ACh receptor.

In an initial step, the enzyme becomes inactivated, but not permanently. Some degree of reactivation of the AChE enzyme occurs in this initial phase, but the process is slow. An additional reaction between AChE and the nerve agent makes their interaction irreversible, a phenomenon known as "aging." For the clinical effect to be reversed after aging occurs, new AChE enzyme must be produced. This irreversible bond is one difference between organophosphate compounds (including nerve agents) and carbamates, which bind reversibly to AChE. This concept is also used for pretreatment of military personnel with the carbamate pyridostigmine.

The typical aging half-lives for the different nerve agents are listed as follows:

  • GA (tabun) - 14 hours
  • GB (sarin) - 5 hours
  • GD (soman) - 2-6 minutes
  • VX - 48 hours
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Epidemiology

Frequency

United States

No instances of binary nerve agent use or intentional release have been reported in the United States.

International

Although G agents were synthesized during World War II, no evidence exists that they ever were used in actual combat. Evidence is available that they were tested in concentration camps, however. The only known instance in which nerve agents were used in combat was during the Iran/Iraq war. The Iraqis also allegedly used them against the Kurds, most infamously at the town of Halabja in 1987. GB was used in Matsumoto, Japan, in 1994, and in the Tokyo subway attack in 1995, in the only two reported terrorist uses of sarin.

The threat of the use of nerve agents in terrorism is pervasive. Countries that are in political turmoil are at a higher risk for terrorist events. An unknown number of countries and terrorist groups may possess or have the capacity to manufacture nerve agents.

No instances have been reported in which the agents have been released in the form of binary weapons.

Mortality/Morbidity

Toxicity of nerve agents is measured in two forms, median lethal concentration (LCt50) and median lethal dose (LD50). The LD50 is the lethal dose to 50% of exposed population, and refers to liquid or solid exposures. LCt50 refers to the inhalational toxicity of the vapor form of a volatile agent. Ct refers to the concentration of the vapor or aerosol in the air (measured as mg/m3) multiplied by the time the individual is exposed (measured in minutes). The LCt50 thus refers to the vapor exposure necessary to cause death in 50% of an exposed population. With an LCt50 of 10 mgXmin/m3, VX is the most toxic of the nerve agents (see Table 1).

Table 1. Toxicity of Nerve Agents (Open Table in a new window)

Agent Chemical Name LCt50, mgXmin/m3 LD50,



mg



GA Ethyl N -dimethylphosphoramidocyanidate 400 1000
GB Isopropyl methylphosphonofluoridate 100 1700
GD Pinacolyl methylphosphonofluoridate 50 100
VX O-Ethyl S-2-diisopropylaminoethyl methylphosphonothioate 10 10

 

Race

Sensitivity to nerve agents varies with the individual, but no studies have addressed differential susceptibility based on race.

Sex

Everyone is at risk of being a target of terrorism. Military personnel are theoretically at increased risk; however, no gender predilection exists. No studies have been performed looking at differential susceptibility to nerve agents according to gender.

Age

Everyone is at risk of being a target of terrorism. Military personnel are theoretically at increased risk; however, no predilection based on age exists.

Some limited evidence exists that children may be more susceptible than adults to the effects of organophosphate insecticides. In animal studies, lethal doses for immature and juvenile rats were 10% and 33%, respectively, of the lethal dose for adult rats.

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