CBRNE – Vesicants, Mustard – Hd, Hn1-3, H
Mustard agents are vesicants (blister agents) used in warfare to produce casualties, degrade fighting efficiency, and force opposing troops to wear full protective equipment. Mustard agents are cytotoxic alkylating compounds and include nitrogen mustards (HN-1, HN-2, HN-3), sulfur mustards (H, HD, HT), and mustard-lewisite (HL). Mustard agents are oily liquids ranging from colorless (in pure state) to pale yellow to dark brown, depending on the type and purity. They have a faint odor of mustard, onion, garlic, or horseradish, but because of olfactory fatigue, do not rely on odor for detection.
Volatility varies with the particular compound. Mustard agents are only slightly soluble in water and are heavier than water; thus, they may persist for long periods. HN-1 is more volatile and less persistent than HD, but it is only one fifth as potent a vesicant to the skin. HN-3 is less volatile and more persistent than HD and has equal vesicant effects.
Mustard agents rapidly penetrate clothing and skin. Chemical protective mask with charcoal filters, chemical protective overgarments with charcoal, and butyl rubber chemical protective gloves and boots afford full protection against mustard agents.
More than two dozen nations may have the capability to manufacture offensive chemical weapons. Mustard agents are simple to manufacture and therefore can be a first choice for countries or terrorists who decide to have a capacity for chemical warfare agents. Mustard agents may be delivered by artillery shell, mortar shell, rockets, bombs, or aircraft spray. Since World War I, mustard use in at least 12 conflicts has been supported by evidence or allegations. Historically, mustard agents are the most widely used type of chemical warfare agent.
Mustard agents constitute both a vapor and a liquid threat. Mustard agents cause tissue damage within several minutes of contact.  No immediate symptomatic or local reaction occurs to mustard vapor or liquid. Decontamination must be performed immediately after contact to prevent injury. A latent period occurs, ranging from 4-12 hours after mild exposure and 1-3 hours after severe exposure, prior to the onset of symptoms. More than 80% of mustard casualties are from vapor exposure, but more severe injuries are caused after contact with liquid mustard agents.
Mustards first were produced in 1822, but their harmful effects were not discovered until 1860. On July 12, 1917, the Germans delivered artillery shells containing HD on a World War I battlefield near Ypres, Belgium. More than 20,000 casualties resulted from this first use of mustard as a chemical warfare agent. Subsequently, mustard agents accounted for 80% of chemical casualties in World War I. Among 6980 cases of mustard burns during World War I, the location of the lesions were as follows: eyes, 86%; respiratory, 75%; scrotum, 42%; face, 27%; anus, 24%; legs, 11%; buttocks, 10%; hands, 4%; and feet, 1.5%. Fewer than 5% of casualties from mustard who reached medical treatment died. Mustard injuries were slow to heal and necessitated an average convalescent period of more than 6 weeks.
Italy allegedly used mustard against Abyssinia in the 1930s. Japan allegedly used mustard agents against the Chinese from 1937-1944.
Nitrogen mustard agents were synthesized in the late 1930s. Mechlorethamine (HN-2) became the prototypical mustard agent used as a cancer chemotherapeutic agent. Germans and Americans started the military production of nitrogen mustard agents in 1941 and 1943, respectively. They have not been used on the battlefield.
Toward the end of World War II, a German air attack on the Italian port of Bari struck a US ship loaded with mustard agent munitions. Large amounts of mustard agents were released to the atmosphere and into the harbor water. Many soldiers and sailors were exposed to the mustard-contaminated water. Of 617 US mustard casualties, 83 died.
During the Yemen War of 1963-1967, Egypt reportedly used mustard bombs against the royalist troops in North Yemen.
During the Iran-Iraq war from 1979-1988, approximately 5000 Iranian soldiers were reported killed by Iraqi chemical agents, 10-20% by mustard agents. Additionally, 40,000-50,000 individuals were injured resulting in many chronic medical problems. [2, 3]
After the February 1991 cease-fire ending the Persian Gulf War, United Nations inspection teams discovered mustard agents at Al Muthanna, Iraq.
Besides the threat of chemical attack, a larger concern may be the tons of mustard agents that were produced for war and then dumped at sea, buried in landfills, or left to decay in storage facilities.  In Sweden, recurring incidents of mustard agent exposures involve fisherman who encounter discarded chemical weapons that were dumped in the waters off the coast after World War II. Before the 1970s, the United States dumped obsolete chemical weapons at sea; three separate incidents of exposure to sulfur mustard munitions were reported. 
Developing nations and terrorist groups can easily obtain HD because of its low cost and availability. The US stockpile of mustard chemical warfare agents currently is undergoing destruction.
Mustard agents are lipophilic and are absorbed readily across intact skin and mucous membranes. The rapid penetration is enhanced by moisture, heat, and thin skin. The physical properties (low volatility and a freezing point of 14o C) of sulfur mustard (H, HD, HT) make it a better weapon for use in warm or hot environments due to a greater risk of vapor inhalation. Approximately 20% of HD is absorbed by the skin, the remainder evaporates. Of the absorbed HD, 10-50% of the mustard dose binds to the skin as reacted (fixed) mustard, and the remaining 50-90% is distributed in the circulation as unreacted (free) mustard to almost all organs and tissues. Because of dilutional effects, systemic effects are observed only at high doses. Mustard is eliminated from the body in the urine as a by-product of alkylation.
No single mechanism or clear understanding exists for the biological damage caused by mustard agents.  The toxic effects of mustards depend on their rapid covalent binding to a large number of biological molecules and in the formation of a reactive cyclic ethylene sulfonium ion. Mustard agent molecules contain 2 reactive binding groups. Mustards can bind to nucleophiles such as nitrogen in the base components of nucleic acids and sulfur in SH-groups in proteins and peptides. Mustards can destroy a large number of cellular substances by alkylation of DNA, which leads to DNA strand breaks and apoptosis.
Mustards also bind to cellular glutathione, a small peptide that is a major free radical scavenger. Glutathione depletion leads to inactivation of enzymes, loss of calcium homeostasis, lipid peroxidation, cellular membrane breakdown, and cell death. Pretreatment of cells with N -acetylcysteine has shown benefit in some studies.
Individual cell death within 2 hours of vapor exposure has been demonstrated in an animal model and general cell necrosis within 12 hours.
The concentration-time product capable of killing 50% of exposures (LCt50) of mustard vapor is 1500 mg·min/m3, and the lethal dose to 50% of exposures (LD50) of liquid mustard on the skin is 100 mg/kg.
Mustards are mutagenic resulting in a slight increased incidence of lung cancer, bladder cancer, and leukemia.
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Daniel J Dire, MD, FACEP, FAAP, FAAEM Clinical Professor, Department of Emergency Medicine, University of Texas Medical School at Houston; Clinical Professor, Department of Pediatrics, University of Texas Health Sciences Center San Antonio
Daniel J Dire, MD, FACEP, FAAP, FAAEM is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Pediatrics, American Academy of Emergency Medicine, American College of Emergency Physicians, Association of Military Surgeons of the US
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Zygmunt F Dembek, PhD, MPH, MS, LHD Associate Professor, Department of Military and Emergency Medicine, Adjunct Assistant Professor, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine
Disclosure: Nothing to disclose.
Fred Henretig, MD Director, Section of Clinical Toxicology, Professor, Medical Director, Delaware Valley Regional Poison Control Center, Departments of Emergency Medicine and Pediatrics, University of Pennsylvania School of Medicine, Children’s Hospital
Disclosure: Nothing to disclose.
CBRNE – Vesicants, Mustard – Hd, Hn1-3, H
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