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CBRNE - Vesicants, Organic Arsenicals - L, ED, MD, PD, HL

  • Author: Geoffrey M Fitzgerald, MD; Chief Editor: Zygmunt F Dembek, PhD, MPH, MS, LHD  more...
 
Updated: Apr 29, 2015
 

Background

Vesicants are a class of chemical weapons named for their ability to cause vesicular skin lesions. The 4 organic arsenicals are lewisite (L), methyldichloroarsine (MD), phenyldichloroarsine (PD), and ethyldichloroarsine (ED). These agents, together with the mustard agents and phosgene oxime, make up the vesicant class. Although not as well known as the mustards, the organic arsenicals are a group of potent vesicants that medical planners should not overlook.

Interest in organic arsenicals dates back to the mid-19th century. While investigating possible new fumigants, European chemists discovered that chloroarsines (ie, arsenic-chloride compound in which 1 of the chlorine atoms is replaced by an organic radical) tended to be destructive both to insects and to human tissue. With the start of World War I, both sides employed chemists to create chemical warfare (CW) agents. The trench warfare stalemate created a tactical need for a chemical weapon that was both short acting (eg, nonpersistent, volatile) and lethal. To fill this need, German chemists delivered the first weaponized organic arsenical, MD.

Two additional organic arsenicals, PD and ED, soon augmented MD. While MD, PD, and ED were being deployed on the battlefields of Europe in 1917 and 1918, a team of American researchers, led by Captain Wilford Lee Lewis of the US Army Medical Corps, was working on the fourth and final organic arsenical. Lewisite, as it was named, never was deployed in World War I.

Although mustard vesicants have been used in numerous regional wars since 1918, organic arsenical weapons have had limited use. Lewisite (L) may have been used by Italy against Ethiopia in 1935 and again by Japan in China from 1937-1944. Lewisite became the primary vesicant stockpiled by the Soviet Union.

Today, arsenicals still are considered a threat, not so much from large nation states but from smaller, less developed nations and/or by terrorist organizations. The relative ease of production coupled with their effectiveness against an unprotected population make organic arsenicals a continued threat in the 21st century.[1]

The Agency for Toxic Substances & Disease Registry has established Medical Management Guidelines for lewisite exposure. These guidelines cover both prehospital and emergency department care.

For patient education information, see the First Aid and Injuries Center, as well as Chemical Warfare and Personal Protective Equipment.

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Pathophysiology

The exact mechanism of biological activity and toxicity of the organic arsenicals is unknown. DNA alkylation and/or inhibition of glutathione-scavenging pathways are 2 postulated mechanisms of action. What is certain is that a blistering reaction occurs on any tissue that an arsenical contacts, whether it is skin, eye, or pulmonary tissue. The onset of symptoms after arsenical exposure occurs in seconds as compared to 4-8 hours for mustard exposure. Either a liquid or vapor (ie, gaseous form of a substance at temperatures below boiling point) can cause toxicity. The organic arsenicals tend to have high volatility at room temperature and thus pose a significant vapor threat to exposed personnel.

Animal data and limited human trials demonstrated that organic arsenicals readily penetrate the skin. Within seconds of contact, the chemical fixes itself to the epidermis and dermis. Pain is immediate. Since the agent penetrates deeper, destruction of subcutaneous tissue results. Protease digestion of anchoring filament at the epidermal-dermal junction occurs. The separation of dermis from epidermis together with capillary leakage causes fluid-filled vesicles.

Vapor contact with the conjunctiva may be the victims' first symptom. Severe conjunctival irritation and blepharospasm result upon eye contact. More severe exposure can cause loosening of corneal epithelial cells and swelling and edema of the cornea.

The respiratory tract's mucosa and submucosa are susceptible to vapor exposure. Mucosal damage starts in the nose and descends down the respiratory mucosa in a dose-dependent fashion. Immediate pain, lacrimation, and irritation accompany the damage. Damaged respiratory mucosa slough off, filling the airways with debris. Damage to the lung parenchyma causes the secretion of blood and mucous that, with the pseudomembranes, can cause asphyxiation. In animal studies, large doses of lewisite (L) caused this "dry land drowning" within 10 minutes.

The gastrointestinal tract also is susceptible. Phenyldichloroarsine (PD) vapor in particular produces a phenyl radical that causes vomiting. Vomiting usually develops within 1-2 minutes after exposure to phenyldichloroarsine (PD).

The immediate onset of symptoms following exposure makes severe or systemic toxicity to organic arsenical unlikely. However, if a victim does not have protective gear or cannot move out of a contaminated area, prolonged contact may lead to multiorgan involvement. Blood-borne arsenicals can trigger increased permeability of capillaries throughout the body. Leakage of proteins and plasma then can cause third space fluid shifts, hypovolemia, and shock. Intravascular hemolysis of erythrocytes with subsequent hemolytic anemia may result.

The National Advisory Committee for Acute Exposure Guideline levels for Hazardous Substances has determined the values for lewisite (see the Table below).[2]

Table. Acute Exposure Guideline Levels (AEGLs) for Lewisite[2] (Open Table in a new window)

Classification 10 min 30 min 1 h 4 h 8 h
AEGL-2 (disabling) 1.3 mg/m3 (0.15 ppm) 0.47 mg/m3 (0.055 ppm) 0.25 mg/m3 (0.030 ppm) 0.070 mg/m3 (0.0083 ppm) 0.037 mg/m3 (0.0044 ppm)
AEGL-3 (lethal) 3.9 mg/m3 (0.46 ppm) 1.4 mg/m3 (0.16 ppm) 0.74 mg/m3 (0.087 ppm) 0.21 mg/m3 (0.025 ppm) 0.11 mg/m3 (0.013 ppm)

 

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Epidemiology

Frequency

United States

Organic arsenical weapons never have been used within the US. Other sources of arsenic poisoning are common, and arsenic ingestion is the most common cause of acute metal poisoning in the US. Inorganic arsenic is found in insecticides, rodenticides, and herbicides and is used in mining and smelting industries.

International

Any nation or terrorist group that has access to a basic pesticide production facility can produce these agents with relative ease. The former Soviet Union is known to have combined sulfur mustard (H) and lewisite (L) into a binary weapon known as HL. Lewisite is more volatile and persistent in colder climates than mustard. Lewisite remains fluid at lower temperatures, which enables it to be dispersible in winter temperatures. Therefore, a sulfur mustard-lewisite mix can be used in lower temperatures than sulfur mustard.

Mortality/Morbidity

Although vesicants have a relatively low mortality rate when compared to other CW agents, survivors usually require prolonged care and rehabilitation. These requirements placed a tremendous burden on the medical infrastructure during World War I.

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Contributor Information and Disclosures
Author

Geoffrey M Fitzgerald, MD Consulting Staff, Concord Emergency Medical Associates

Disclosure: Nothing to disclose.

Coauthor(s)

Timothy Vollmer, MD 

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Chief Editor

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

Zygmunt F Dembek, PhD, MPH, MS, LHD is a member of the following medical societies: American Chemical Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

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.

References
  1. Devereaux A, Amundson DE, Parrish JS. Vesicants and nerve agents in chemical warfare. Decontamination and treatment strategies for a changed world. Postgrad Med. 2002 Oct. 112(4):90-6; quiz 4. [Medline].

  2. [Guideline] Committee on Acute Exposure Guideline Levels; Committee on Toxicology; Board on Environmental Studies and Toxicology; Division on Earth and Life Studies; National Reserch Council. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 15. 2013 Sep 26. [Medline]. [Full Text].

  3. Comptom JA. The arsenicals. Military Chemical and Biological Agents: Chemical and Toxicological Properties. 1987. 17-43.

  4. Ford MD. Metal and metalloids. Emergency Medicine: A Comprehensive Study Guide. 5th ed. 2000. 1185-1191.

  5. Ford MD. Arsenic. Goldfrank's Toxicology Emergencies. 6th ed. 1998. 1261-1270.

  6. Karalliedde L, Wheeler H, Maclehose R, Murray V. Possible immediate and long-term health effects following exposure to chemical warfare agents. Public Health. 2000 Jul. 114(4):238-48. [Medline].

  7. NATO. Blistering agents. Emergency War Surgery NATO Handbook. 2nd US revision. 1988. 88-90.

  8. Hurst CG, Petrali JP, Barillo DJ, Graham JS, Smith WJ, Urbanetti JS, et al. Vesicants. Shirley D. Tourinsky. Medical Aspects of Chemical Warfare. Washington, D.C.: Borden Institute; 2008. 259-310. [Full Text].

 
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Table. Acute Exposure Guideline Levels (AEGLs) for Lewisite [2]
Classification 10 min 30 min 1 h 4 h 8 h
AEGL-2 (disabling) 1.3 mg/m3 (0.15 ppm) 0.47 mg/m3 (0.055 ppm) 0.25 mg/m3 (0.030 ppm) 0.070 mg/m3 (0.0083 ppm) 0.037 mg/m3 (0.0044 ppm)
AEGL-3 (lethal) 3.9 mg/m3 (0.46 ppm) 1.4 mg/m3 (0.16 ppm) 0.74 mg/m3 (0.087 ppm) 0.21 mg/m3 (0.025 ppm) 0.11 mg/m3 (0.013 ppm)
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