CHEMICAL WARFARE

INTRODUCTION In some sense all warfare could be called chemical warfare because every modern weapon depends upon some sort of chemical explosion to cause some sort of casualty. We will narrowly limit the phrase chemical warfare to refer to the type of warfare that employs weapons which use the toxic properties of certain chemicals to produce debilitating physiological and / or psychological effects on the enemy. Additionally, a chemical agent is a chemical compound that is used in chemical warfare. The threat of terrorism on US soil, to include chemical warfare, has become so great that a whole new agency of the government is being formed to counter this threat. An estimated 34 countries, to include the US, have the capability to produce chemical agents as well as certain subnational groups. The threat of chemical warfare has increased dramatically since the 1980s. Chemical agents, mustard and tabun, were used in the Iran - Iraq war. The most notable terrorist activity using chemical weapons during peacetime occurred during the morning hours of 20 Mar 1995 on a subway train headed for the central government district in Tokyo. Members of the Aum Shinre Kyo cult, a Japanese doomsday cult, punctured bags of sarin gas (a chemical age nt) on the subway, killing 12 people and injuring many more. This was not the first time chemical agents have been used. The first employment of chemical weapons in modern times was by the Germans at Ypres, Belgium, on 15 April 1915. That afternoon German units released an estimated 150 tons of chlorine gas against Allied troops. Its use was largely superceded by the use of phosgene, COC12 , a more dense vapor. Because of its density, phosgene does not rise as rapidly as chlorine gas, as the cloud of gas passes over the target area. Still later in the war sulfur mustard (a liquid at ambient temperatures) was introduced. Sulfur mustard persisted in the area of impact meaning it did not readily evaporate. This agent remained as a hazard for a considerable period of time, thus acting as a barrier to troop movements. Mustard was subsequently used extensively and with decisive results by Italy in Ethiopia in 1935. The organo-phosphorous compounds, also known as nerve agents, are considered the most dangerous class of chemical agents. These agents were first developed in the 1930's, by the German scientist Gerhard Schrader, in conjunction with his research on insecticides. There are both persistent and non-persistent varieties. Nerve agents are a major component of the chemical arsenals of both the U.S. and the former U.S.S.R. Chemical agents may be delivered by a wide variety of means: bombs; spray tanks; rockets; missiles; land mines; and artillery projectiles. Just the threat of their use can force military personnel to don cumbersome and uncomfortable protective clothing, thereby, greatly reducing their military effectiveness without any direct casualties.

In 1974, the U.S. signed the Geneva Protocol of 1925, which bans the use of poisonous substances in war. The U.S. reserved the right to retaliate in kind if an enemy uses any chemical agent against the US. The power to order such retaliation resides with the President. The U.S. has additionally renounced the use of herbicides and riot control agents in war, except in retaliation. (President Ford, 1975). There are six types of chemical agents that this chapter will deal with: pulmonary agents, cyanide, vesicants, nerve agents, incapacitating agents and riot cont rol agents. In addition, a brief description of smoke and flame weapons is included at the end of the chapter. This information is summarized from the United States Army Medical Research Institute of Chemical Defense (ICD) Medical Management of Chemical Casualties Handbook. A review of this handbook is recommended for more in-depth information. Table 1 shows the chemical agents discussed in this chapter. PULMONARY AGENTS Inhalation of pulmonary agents results in varying degrees of lung damage, agent dependent. They act by damaging the capillaries in the lungs causing the seepage of a watery fluid into the air sacs (pulmonary edema (swelling)). This fluid interferes with oxygen uptake and the victim dies of oxygen deficiency. The most common agent of this type, phosgene, is believed to act through its hydrolysis in the lungs to yield hydrochloric acid (see diagram below). The exact mechanism of toxicity for pulmonary agents is unknown and there is no specific antidote for this type of poisoning.
O Cl Cl O

2 H2O HO OH

2 HCl

Besides being a chemical agent, phosgene is also an important industrial chemical, widely used to produce dyes and polyurethane plastics. It was first produced by John Davy in 1812 and was first used on the battlefield by Germany in 1917. It is no longer a component of the U.S. arsenal. CYANIDE The term cyanide refers to the CN anion but members of this class of agents also include anything that produces CN in the body. Thus, hydrogen cyanide (HCN), and cyanogen chloride (ClCN), are the main chemical agents in this class. An older term, that is still often encountered, for this class of agents is the blood agents. This term was used early on because of the observed systemic effects of cyanide exposure (as opposed to more local effects of other types of agents). The term is somewhat antiquated now however because it is now known broad, systemic effects are the hallmark of many other agents as well (the nerve agents, for instance). These agents are delivered to the target area as liquids enclosed in munitions and rapidly vaporize upon munition detonation. The y are inhaled and form the cyanide anion, CN-. The anion is then distributed to virtually every organ and tissue of the body. The body has the ability

to detoxify small amounts of CN at a certain rate, thus the lethal dose is actually timedependent. For instance, a given amount of CN absorbed over a long enough time period may have no physiological effects. But, the same dose administered all at once could be lethal. Their mechanism of action is the interference of oxygen metabolism. In particular cyanide binds to the cytochrome oxidase enzyme as a ligand. The blocked enzyme is now unable to do its primary role assist with intracellular oxygen utilization. The gas historically used in "gas chambers" for the execution of criminals is this type of agent. Anidotal therapy is a two part process for cyanide patients. The first step involves a methemoglobin- forming agent such as amyl nitrite, CH3 CH2 CH2 CH2 CH2NO2 or sodium nitrite, NaNO2 . These are oxidizing agents that function by oxidizing Fe (II) hemoglobin to the Fe (III) form, which then binds the cyanide preferentially. The next step is to provide a sulfur donor in order to convert the cyanide to thiocyanate. Sodium thiosulfate (Na2 S2O3 ) is used for this purpose. A possibly more effective antidote with fewer undesirable side effects is alpha-keto glutaric acid. Blood agents are non-persistent agents. Decontamination, if necessary, may be effected by oxidation of the cyanide under basic conditions by hypochlorite (OCl ) to give CO2 and N2 . VESSICANTS Vessicants are also known as blister agents. These most common effects of blister agents are: edema (swelling) and blisters on the skin: irritation, conjunctivitis, corneal opacity and other damage to the eyes; and mild to remarkable respiratory damage. They also have gastrointestinal effects and suppress bone marrow stem cell production. Sulfur mustard and the nitrogen mustards are the main threat agents while two more, lewisite and phosgene oxime, constitute a minor threat. Sulfur mustard, 2-chloroethylsulfide (see figure below), is an oily liquid with a low volatility. It is mainly a liquid hazard but at temperatures above 100 F, it is also considered a vapor hazard (much more dangerous). This agent readily penetrates thin fabrics and is highly absorbed through the skin first forming a sulfonium chloride, which then attacks cell proteins, alkylating free amino and hydroxyl groups causing general destruction of tissue. The end result is the formation of large water blisters by an as of yet undetermined mechanism of action.
H2 C Cl C H2 H2 C C H2 Cl Cl H2 C HS C H2

H2 C

+ C H

These agents, especially sulfur mustard, have been major threats since WWI. Mustard binds irreversibly to tissue within minutes of initial exposure and therefore immediate decontamination is really the only effective way to minimize the effects. There is no specific antidote to counter the effects of these agents, and their effects are often delayed, appearing hours after initial exposure and. Treatment of victims consists of protecting the blisters from infection.

NERVE AGENTS Nerve agents act at cholinergic synapses. A synapse is the small space between a nerve ending and an adjacent nerve or between a nerve ending and a muscle cell. Cholinergic synapses are those at which the chemical mediator, or messenger, acetylcholine, is liberated by the nerve ending. We find cholinergic synapses in the parasympathetic nervous system and the peripheral nervous system. The role of the parasympathetic nervous system is to bring about changes that are designed to conserve and restore the energy sources of the body. A good portion of the peripheral nervous system is devoted to innervation of skeletal muscle, i.e. those muscles which allow body movement and breathing. Although acetylcholine is the chemical mediator in both systems, it has two different effects: it causes "relaxation" of the target organs of the parasympathetic system and causes contraction of the skeletal muscle. Let us consider muscular innervation first. When an impulse (electrical signal) reaches the end of a nerve cell, acetylcholine is liberated. The acetycholine reacts with adjacent muscle cell membrane, causing the membrane to depolarize and the muscle to contract. If acetylcholine were to accumulate at the synaptic junction, the muscle would be in a continual state of contraction. Normally, after the acetylcholilne stimulates the muscle, it is inactivated via hydrolysis by the enzyme acetylcholinesterase. Nerve agents (and many insecticides) strongly bind or react with acetylcholinesterase, destroying its ability to hydrolyze acetylcholine. The physiological result is sustained muscular contraction; hence, inability to move or breathe. In the parasympathetic system, the nerve agent once again prevents hydrolysis of the acetylcholine. The buildup of acetylcholine in the synapses of this system results in pupillary constriction, stimulation of salivary secretion, stimulation of the lacrimal gland (ie, tearing), cardiac inhibition, bronchoconstriction, increased peristalsis of the stomach and small intestine and relaxation of the sphincters, and contraction of the smooth muscle of the lower bowel. The equation below shows how the agent "GB" reacts with the enzyme acetylcholinesterase. Nerve agents inactivate cholinesterase either by complexing the enzyme or by reacting covalently with the active site of this enzyme, thereby impairing its ability to hydrolyze acetycholine.
Active Site ser CH2 HO ..: Sarin O F P O CH CH 3 CH3 (esteratic site only) CH3 ser CH2 O O P O CH CH3 CH 3 Inactivated Enzyme CH3 + HF

ser

CH2

O F P CH3 O CH CH3 CH3

It is instructive to note the factors which make one nerve agent more toxic than another. Since the phosphorus atom of the agent attacks the electronegative atom at the active site of the enzyme, substituents which withdraw electrons from the phosphorus atom making it even more electropositive, will increase the agent's toxicity. This explains why the nerve agent GB is more toxic than the insecticide dimefox, where electron donating amine groups are present.
H3C HC H 3C O O P CH3 F H3C H3C H 3C N O P N CH3 F

GB

DIMEFOX

The principal U S. nerve agents are GB and VX (see Table ) while the former Soviet mventory has been said to consist primarily of GB, GD, and thickened GD (TGD). This last is prepared by the addition of a polymeric substance to the neat , liquid agent to form a gel of varying consistency which can adhere to surfaces, significantly increasmg the pers~stency of the agent and making decontamination difficult. Decontamination of GB and GD is most easily effected via hydrolysis with aqueous sodium hydroxide, while calcium hypochlorite is the standard decontamlinant for VX. The agents, however, are quite effective at diffusing into the pores of most materials, including metals, where a cursory decontamination effort may not reach them. This, coupled with their extremely high toxity, raises the possiblity of dangerous agent concentrations building up in the vicinity of cleaned" equipment via later outgassing. More information on nerve agents can be found in the biopolymers chapter. There, the enzyme acetylcholinesterase and its inhibition by nerve agents such as sarin serves as a case study in the exploration of protein structure and enzyme function. INCAPACITATING AGENTS Incapacitating agents are non- lethal chemical warfare agents that have the opposite effect on the body as nerve agents. These anticholinergic agents are competitive inhibitors of acetylcholine at certain post synaptic and postjunctional muscarinic sites. They are designed to create a stupor like effect as well as confusion and possibly even hallucinations. The use of these agents dates to at least 600 BC when he llebore roots were thrown into a stream to contaminate the drinking water of the enemy to give them diarrhea. Bz or QNB (3-quinuclidinyl benzilate) is the major incapacitating threat. It is odorless and nonirritating. It, like vesicants, has a delayed onset time. Symptoms do not manifest themselves until approximately 30 minutes to 24 hours after exposure.

RIOT CONTROL AGENTS Most people have at least heard of one agent in this classification before, teargas. Riot control agents are mainly irritants designed to cause discomfort and temporary eye closure to incapacitate the victims. They cause burning, pain or disconfort when they come into contact with skin and exposed mucous membranes. They have a relatively quick onset time (seconds) and linger for a few minutes after the agent is removed. There were many agents to have this classification but only two, CS and CN, are mainly used today. . SMOKE Smoke has taken on a new military significance in recent years, because it is an effective defense against laser and optically guided munitions. The easiest way to make smoke is to vaporize oil. A simple way to do this is by injecting the oil onto a hot exhaust manifold, and then let the oil recondense as small droplets. The many tiny droplets refract and scatter incident light in a manner such that they appear collectively as an opaque white cloud i.e. smoke. There are two important additional ways of chemically producing smoke. One is with an HC mixture, the other is with phosphorus. HC is a burning mixture containing grained aluminum, zinc oxide, and hexachloroethane. 9/2 O2 + 2 Al +9 Zn + 3 C2 C16 A12 O3 + 9 ZnC12 + 6 CO + heat The ZnC12 picks up water from the air to produce particles of effective screening size. HC is used in grenades, candles, pots and artillery shells. A second method involves the use of white phosphorus (WP) which burns when it comes in contact with air, producing P2 O5 . The P2 O5 then absorbs water from the air, forming small droplets of H3 PO4 (phosphoric acid). Artillery shells filled with WP are also used for their incendiary effect. FLAME WEAPONS Flame weapons, or incendiaries, can be broken down into two general classes; oil and metal. The most familiar incendiary, napalm, is merely gasoline or some similar fuel to which a detergent-like thickener such as the M4 thickener shown below is added.
H2 C H2 H2 C H C C C H2 O O

H3C

O O

Al3+

M4 Thickener

The particles of thinkener absorb the fuel, expanding until the entire mass is a homogeneous gel. Thickener is used to slow the burning, improve clinging properties, and cause the fuel to rebound off walls and go around corners. In the M202 incendiary rocket (an infantry weapon) triethyl aluminum is added to cause spontaneous ignition when the fuel is exposed to air. (Al(C 2 H5 )3 is pyrophoric). Thermite is the major metal incendiary. It is essentially a mixture of powered iron oxide and granular aluminum. A redox reaction takes place, generating much heat and molten iron. Fe2 O3 + 2 Al A12 O3 + 2 Fe + heat Often, the casing of a thermite bomb is made from magnesium, which is flammable itself, burning with a hot, white flame that can also serve as the igniter for the thermite mix. Mg + O2 MgO2 + heat

Table 1 Chemical Agents

Chemical Name (Military Symbol) Structure Physical state (at 20 C) Aveg. Lethal Dose (mg min/m3 ) 1600 Physiological Action

Phosgene (CG)

O Cl C
HCN

Colorless Gas

Pulmonary edema

Cl
Colorless Gas Colorless Gas Colorless to pale yellow liquid Dark liquid 5000 Interferes with bodys use of O2 Similar to AC, also choking Destroys tissues, causes blisters Same as HD

Hydrogen Cyanide (AC) Cyanogen Chloride Sulfur Mustard, 2-Chloroethylsulfide (HD) N Mustard, 2,2,2Trichlorotriethylamine (HN-3) Sarin, Isopropoxy metylphosphonofluoridate (GB) Pinacoyl methyl phosphonofluoridate (GD)

CNCl (ClCH2 CH2 )2 S

7000 10000

ClCH2 CH2 )3 N

10000

CH3 CH O CH3
CH3 CH3 C
H 3C

O P F
O CH O P F CH3

CH3

Volatile liquid

100

Paralysis leading to cessation of convulsions same as GB

CH3 CH3
O-ethyl-S-2-diisopropylaminoethyl methylthiophosphonate (VX)
CH N CH H 3C CH 3 CH 3 CH 2 S P

liquid (less volatile than GB) Colorless liquid

100

75

Same and GB O-ethyl

OCH 2CH 3

CH 3

Chloroacetophenone (CN)

O Cl

Solid (dispersed as smoke)

11000

Lacrimatory; irritates respiratory tract

ortho-Chlorobenzyl malononitrile (CS)

Cl CN CN

Solid (dispersed as smoke/fine powder)

25000

Highly irritating, but not toxic