Since the terror attacks of September 11, 2001, policymakers have been attempting to decreasethe vulnerability of the United States to the terrorist use of weapons of mass destruction. This reportdescribes the different types of high-threat chemical agents. It also discusses their availability,treatment, and detection, and possible policy approaches to reducing the threat posed by them. Terrorist use of chemical agents is widely believed to be an event that has low probability, but potentially high consequences. While there is still debate over whether terrorist groups have anincreased interest in chemical acquisition and use, the domestic vulnerability of the United Statesto chemical attack remains high. Policy approaches to reducing chemical vulnerability havegenerally treated chemical agents as a group, rather than addressing specific agents. Additionally,military and civilian chemical agent detection have developed with little coordination, so thatcivilian toxic industrial chemical kits and military chemical weapons detectors having varyingsensitivities and detection capabilities. Treatments for chemical exposure vary as well, dependingon the type of chemical, and so must be addressed on a chemical by chemical basis. Becausecomparatively few individuals have been exposed to modern chemical weapons, practical experiencein treatment of chemical casualties is limited, especially among civilian health care providers. Whilenational efforts to reduce vulnerability to terrorist chemical agent use continue, it is not clear whetherspecific agents that pose the greatest danger are being adequately addressed as general vulnerabilitiesare being reduced. High-threat chemical agents are, for the purpose of this report, chemicals posing exceptionallethality and danger to humans. (1) Some may havebeen developed and used for commercial purposes. Others may have been used or developed by militaries as chemical weapons. Different chemical weapons cause different symptoms in and injuries to their victims. Because of this range of potential symptoms, it can be difficult to know what treatment will be most effectivefor a victim until the chemical or chemical type has been identified. Also, chemical weapons mayproduce their effects by different exposure routes, for example, by skin contact or by inhalation. Asa consequence, depending on what chemical is encountered, different protective equipment must beemployed; for example, a gas mask alone is not sufficient protection against chemicals which candamage through skin contact. Military planners categorize such agents into four classes: nerve, blister, choking, and bloodagents. (2) This categorization groups chemicals bythe effects they cause to those exposed to them. While the nerve and blister agents are predominantly only manufactured and used by militaries asweapons, both choking agents and blood agents include chemicals widely used in industrialprocesses. Chemical weapons affecting the nervous system are called nerve agents. Nerve agents do not occur naturally. Rather, they are manmade compounds that require manufacture and isolation forhigh toxicity and purity. Most nerve agents belong to a group of chemicals called organophosphates. Organophosphates have a wide range of toxicity, and some are commercially employed asinsecticides, though these are significantly less toxic than those developed as chemical weapons. (3) Nerve agents are mainly liquids. Production. The first nerve agent developed for military use, called Tabun or GA, was made in Germany in the 1930s. (4) Following this discovery,a series of nerve agents similar to Tabun were developed. This series, known as the G-series, includethe weapons Sarin (GB) and Soman (GD). In the late 1940s, another series of nerve agents, theV-series, was invented in England. Both the British and the United States chemical weaponsprograms investigated these compounds. The United States manufactured and stockpiled VX. (5) Arelated compound, V-gas, was manufactured and stockpiled by the Soviet Union. Military use ofnerve agents has been rare. Nerve agents were not used during World War I or World War II. During the 1980 -- 1988 Iran-Iraq war, Iraq reportedly used nerve agents against Iranian troops andlater against members of its Kurdish population in northern Iraq. (6) National chemical weapons programs have produced nerve agents for decades. The technological barriers for a terrorist group to synthesize these agents might be overcome by usingcommercially available equipment, though there would be appreciable danger to the manufacturerdue to the extreme toxicity of these compounds. Nerve agent production requires the use of toxicchemicals during synthesis and specialized equipment to contain the nerve agent produced. Of thenerve agents, VX has been identified as the most difficult to manufacture. (7) Effects. Nerve agents are extremely dangerous and can enter the body through the lungs or by skin contact, though for the G-series nerve agents, theinhalation toxicity is significantly greater than the dermal toxicity. Of the nerve agents, VX is themost deadly and Tabun is the least deadly, though all are exceedingly toxic. Nerve agents interfere with the nervous system, causing overstimulation of muscles. Victims may suffer nausea and weakness and possibly convulsions and spasms. At high concentration, lossof muscle control, nervous system irregularities, and death may occur. The action of nerve agentscan be irreversible if victims are not quickly treated. Treatment. Two drugs, atropine and pralidoxime chloride, are used as antidotes for nerve agents. (8) Atropine prevents muscle spasm and allows thebody time to clear the nerve agent. Pralidoxime chloride limits the effects of nerve agent exposureby reversing the agent's action. Both of these drugs were issued to U.S. troops during the PersianGulf War in the form of an antidote kit called the Mark I. Diazepam (Valium) may be used to reduceconvulsions and seizures brought on by exposure to nerve agents. (9) The treatment window for nerve agent exposure is agent-dependent. Some agents quickly and irreversibly react to enzymes within the body, while others require a much longer time topermanently bind to these enzymes. The most effective treatment occurs before such permanentbinding has taken place. Soman, for example, is permanently bound within minutes, while Tabunis not and can be treated up to several hours after exposure. Prophylactic use of some compounds,such as pyridostigmine bromide, may create a larger window for effective treatments for some nerveagents. (10) Blister agents, also known as vesicants, are chemicals that cause painful blistering of the skin. While such blistering is not generally lethal, the excruciating pain caused by blister agents requiresfull body protection against these chemicals. Militarily, blister agents produce casualties and reducethe combat effectiveness of opposing troops by requiring them to wear bulky protective equipment. (11) The most common blister agent is mustard agents, which includes nitrogen- and sulfur-basedcompounds. Mustard agents are oily liquids which range in color from very pale yellow to darkbrown, depending on the type and purity, and have a faint odor of mustard, onion or garlic. (12) Theseliquids evaporate quickly, and their vapors are also injurious. Blister agents are not naturally occurring compounds. Mustard agents, for example, were first developed in the late 1800s. During World War I, both sides in the conflict used these weaponsagainst their enemies, and the mustard-type blister agent produced the greatest number of chemicalcasualties during World War I, though fewer than 5% of these casualties died. Many countries havestockpiled blister agents in their chemical weapon inventories. Mustard agent was also reportedlyused in the Iran-Iraq war. (13) The United States iscurrently destroying its stockpile of blister agents. Production. Production of blister agents is considered less complicated than that of nerve agents. (14) Likenerve agents, it requires the use of some toxicchemicals and specialized equipment to contain the agent produced. The most common blisteragents have many different methods for their production published in the open literature. (15) Effects. Blister agents can enter the body through the lungs or by contact with the skin or eyes. Some can penetrate through normal clothing material,causing burns in areas that were covered by cloth. While blister agents react quickly upon skincontact, their symptoms may be delayed. In the case of mustard agent, damage occurs within 1-2minutes of exposure, but symptoms do not manifest for several hours. (16) As even low concentrationof vaporized blister agent quickly causes damage, it is unlikely that agents will be removed from theskin prior to injury. The initial symptoms of blister agent exposure are a reddening of the skin, resembling sunburn, combined with pain in the effected area. Swelling, blisters, and lesions may then develop dependingon the degree of exposure. Systemic symptoms such as malaise, vomiting, and fever may alsodevelop in extreme cases. (17) Exposure to largeamounts of liquid mustard agent may prove fatal. (18) The eyes are also very sensitive to blister agents. At high vapor exposures, great pain, corneal damage, and scarring between the iris and lens may occur. The most severe eye damage is oftencaused by liquid agent, either from contact with airborne droplets or by self-contamination of theeyes from contaminated clothing or body parts. (19) Victims inhaling blister agents may suffer damage to their lungs. While a single, low-level exposure will likely produce only temporary impairment, high concentrations or repeated exposuresmay cause permanent damage. Inhalation victims may have symptoms ranging from mild bronchitisto blistering of the lungs. (20) Treatment. Damage from blister agent exposure, lesions and other skin irritations, is symptomatically treated. Hospitalization may be required forrespiratory tract injuries. Victims who suffer severe lung damage may require mechanicalventilation.