CWAs (as defined by the Chemical Weapons Convention) may be classified by their physiological effects on humans, routes of exposure, and duration of hazard (persistence) (see Table 2). Classification by physiological effect yields choking (pulmonary agents), nerve, blood (cyanide compounds), blister (vesicants), or central nervous system (CNS)-acting agents (see Table 3 for example chemicals).30, 31, 32
Table 2: Chemical Warfare Agent Classifications
Classification method | Agent classification |
---|---|
Physiological effect | Choking Nerve Blood Blister CNS-acting |
Route of exposure | Inhalation Ingestion Absorption through skin and/or mucous membranes |
Duration of hazard | Persistent Non-persistent |
Persistent agents can be generally described as being low in volatility; they can remain on surfaces or in environmental materials and surfaces for several days, weeks, or longer, presenting long-term inhalation and contact hazards. Non-persistent agents can generally be described as highly volatile; they do not remain on surfaces for extended periods of time and can be considered short-term contact and inhalation hazards.33 However, even non-persistent agents can remain for extended periods on certain media, such as polymeric or porous substances, and in enclosed spaces. Therefore, the length of time any chemical contaminant persists will depend on what materials and surfaces have been contaminated, the state of matter of the chemical (e.g., liquid, solid, gas), and environmental conditions (temperature, humidity, etc.). Additionally, some CWAs can degrade into hazardous/toxic by-products.
Routes of Exposure
There are three main routes of exposure for chemical agents into the body: inhalation, absorption, and ingestion.
Inhalation occurs when a plume of toxic gases, vapors, aerosols (mists) or particulates (dusts or liquid droplets) are drawn (inhaled) into the lungs. Although inhalation is possible for all chemical agents, it is more of a risk with chemical agents having high volatility and low boiling points, such as the G- agents and many toxic industrial gases (e.g., chlorine, ammonia, phosgene).
Absorption is the transport of chemicals from outer surfaces into the body through contact with the skin (dermal). Chemical agents that remain in liquid form due to their chemical and physical properties present the greatest risk for dermal absorption. Although absorption is possible for all chemical agents, it is more of a risk with chemical agents having low volatility and high boiling points, such as the sulfur mustard, V-agents and Novichoks. A secondary route of absorption is ocular, where chemicals are absorbed directly into the body through the eyes from liquid splashes or contaminated vapors or atmospheres.
Ingestion occurs when contaminated foods and water are consumed. Smoking and other hand-to- mouth activities can also lead to the ingestion of chemical agents. Although ingestion is possible for all chemical agents, it is more of a risk with chemical agents having low volatility and high boiling points, such as the sulfur mustard, V-agents and Novichoks.
While a chemical agent with high volatility and low boiling point presents the greatest risk of inhalation from contaminated plumes, these plumes can recondense as liquids and become absorption and ingestion risks at significant distances from the initial release site.
Another, but more uncommon route of exposure, is injection, where a chemical agent is introduced into the body through an injury, open cut, puncture, or intravenously.
Table 3: Examples of Chemical Warfare Agents and Their Physiological Effect Classifications
Agent name | Symbol | Physiological effects | Chemical Abstract Service Number |
---|---|---|---|
Carbonyl chloride (phosgene) | CG | Choking | 75-44-5 |
Diphosgene | DP | Choking | 503-38-8 |
Chloropicrin | PS | Choking | 76-06-2 |
Tabun | GA | Nerve | 77-81-6 |
Sarin | GB | Nerve | 107-44-8 |
Soman | GD | Nerve | 96-64-0 |
Cyclosarin | GF | Nerve | 329-99-7 |
O-Ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate | VX | Nerve | 50782-69-9 |
Novichok | A-230 | Nerve | 2387496-12-8 |
Novichok | A-232 | Nerve | 2387496-04-8 |
Novichok | A-234 | Nerve | 2387496-06-0 |
Hydrogen cyanide | AC | Blood | 74-90-8 |
Cyanogen chloride | CK | Blood | 506-77-4 |
Sulfur mustard | HD | Blister | 505-60-2 |
Nitrogen mustard | HN-1 | Blister | 538-07-8 |
Nitrogen mustard | HN-2 | Blister | 51-75-2 |
Nitrogen mustard | HN-3 | Blister | 555-77-1 |
Lewisite | L | Blister | 541-25-3 |
3-Quinuclidinyl benzilate | BZ | CNS-acting | 6581-06-2 |
Choking (or pulmonary) agents target primarily the airways. They irritate the eyes and respiratory tract, damage the lung and associated tissues, and cause pulmonary edema (also known as “dry-land drowning”). Early symptoms of exposure to choking agents include coughing, choking, a feeling of tightness in the chest, and nausea. Examples include carbonyl chloride (CG, or phosgene), diphosgene (DP), and chloropicrin (PS). There is no antidote for choking agents. Treatment is supportive.34, 35 Most choking agents are, generally, non-persistent.
Nerve agents include some of the most toxic CWAs. All of these agents affect the nervous system by inhibiting the enzyme acetylcholinesterase (AChE). Without functioning AChE, the neurotransmitter acetylcholine builds up and over-stimulates muscles, glands and other structures. Symptoms of nerve agent exposure include miosis (contraction of the pupils), headache, runny nose, salivation, and tightness in the chest. Symptoms of severe exposure include generalized muscular twitching, weakness or paralysis, convulsions, and cessation of respiration. The onset of symptoms for inhalation exposure ranges from seconds to minutes, and for cutaneous exposure from minutes to hours. Nerve agents also can have a cumulative health effect due to a slow metabolism in the body. Examples of nerve agents include tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), O-Ethyl S-(2-diisopropylaminoethyl), methylphosphonothiolate (VX), and Fourth Generation Agents (FGAs) or “Novichok” agents.36 Atropine, pralidoxime chloride (also called 2-pyridine aldoxime methyl chloride [2-PAM Cl]), diazepam, and idazolam are available as antidotes to nerve agent poisoning.37—42 The G-series agents tend to be non-persistent to moderately persistent, while VX and FGAs are considered highly persistent.
Blood agents interfere with oxygen use at the cellular level. They represent inhalation, ingestion, and dermal hazards, entering the bloodstream and other body tissues where they exert one of two effects. Some, such as hydrogen cyanide (AC), cyanogen chloride (CK), and other cyanide-containing compounds, act as cellular poisons and disrupt the oxidative metabolism of cells, while others, e.g., sodium fluoroacetate and arsine, induce hemolysis of red blood cells. Symptoms of blood agent exposure (e.g., to CK) include giddiness, headache, faintness, confusion, palpitation, chest pain, difficulty breathing, convulsions, loss of consciousness, and cardiac arrest. Lacrimatory (tearing of the eyes) effects are also shown with CK. Agent-specific antidote therapies are available to treat exposure to some blood agents; however, most require treatment soon after exposure.43 Blood agents tend to be less persistent than other chemical agents.
Blister agents (or vesicants) generate reddening and blistering of any exposed part of the body. Some of these agents may also damage respiratory and gastrointestinal (GI) mucous membranes. Examples of blister agents include sulfur mustard (HD), nitrogen mustard (HN), Lewisite (L), and phosgene oxime (CX). Often, the physical effects from exposure to a blister agent may not be obvious for hours. However, exposure to Lewisite will yield almost immediate pain. As with nerve agents, a cumulative effect occurs with blister agent exposures. Blister agents are persistent. Decontamination of the exposed area as soon as possible is critical to prevent tissue damage. Effective treatment regimen includes reducing exposure and providing supportive care. Silverlon wound dressings (impregnated with silver) are FDA-cleared to treat skin injury caused by sulfur mustard. Lewisite exposure can be treated using dimercaprol (British Anti-Lewisite), a chelating agent.
Central Nervous System CNS-acting acting chemicals such as analgesics, anesthetics, and sedatives target the central nervous system and cause respiratory depression and other CNS depressive effects. Fentanyl and fentanyl analogs are well-known CNS-acting chemicals that are opioid receptor agonists. Fentanyl is highly potent; the amount of fentanyl in a lethal dose is similar to that for traditional nerve agents. 44, 45 Naloxone is an opioid receptor antagonist that counters all opioid receptor agonists.