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

Author: Geoffrey M Fitzgerald, MD, Consulting Staff, Concord Emergency Medical Associates
Coauthor(s): Timothy Vollmer, MD, Consulting Staff, Department of Emergency Medicine, Geisinger Medical Center
Contributor Information and Disclosures

Updated: Mar 24, 2009

Introduction

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, lead by Captain 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.

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

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.

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.

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.

Clinical

History

Victims of an lewisite (L) attack may remember observing puddles of a brown liquid or of smelling an odor similar to geranium. Methyldichloroarsine (MD) and ethyldichloroarsine (ED) reportedly smell like rotting fruit. Almost instantaneous pain and irritation of the skin, eyes, and nasal pharynx follow exposure. The patient usually relates a history of trying to remove himself or herself from the noxious stimuli.

• The skin burns and itches. A history of erythema followed by the appearance of vesicles may be obtained.
• Eye pain is severe and is accompanied by blepharospasm and/or photophobia.
• Extreme irritation of the nasal mucosa and upper airway induces coughing and sneezing. Coughing may become productive, and shortness of breath may appear as the irritation of the airway mucosa progresses.
• Phenyldichloroarsine (PD) often precipitates severe vomiting within 1-2 minutes after exposure.

Physical

Physical signs of organic arsenical exposure are similar to those of mustard agents. The major difference is the time of onset of signs. Organic arsenicals cause immediate signs, whereas signs of mustard exposure appear after a latent period of several hours.

• An erythematous rash appears within 15-30 minutes. This is followed by the development of fluid-filled vesicles.
  • Vesicles initially are filled with clear fluid and may coalesce to form large bullae.
  • In more severe exposures, the vesicular fluid may take on a yellow and then red color, and a central area of necrosis may form.
  • An lewisite (L) skin lesion has more actual tissue destruction (but less surrounding erythema) than a mustard lesion. Compared to distilled mustard, lewisite (L) is gram-for-gram more toxic. The LD50 (lethal dose for 50% of the population) of lewisite (L) is 2.8 g on the skin.
• Conjunctival injection and edema of the lids, cornea, and conjunctiva occur with either a vapor or liquid exposure.
  • Corneal vascularization with secondary edema results and may last for weeks.
  • One drop of liquid lewisite (L) on the cornea can cause severe corneal damage up to and including perforation.
• Vapor damage to the upper respiratory mucosa causes epistaxis, massive rhinorrhea, and lacrimation.
  • Laryngitis and dysphonia changes result from exposure and can lead to laryngospasm.
  • With larger vapor exposure, destruction of the bronchiolar mucosa and submucosa causes pseudomembrane formation and obstruction.
• Systemic signs of organic toxicity may include evidence of hypovolemia and shock.

Causes

Organic arsenical exposure can be caused by military chemical warfare (CW) attack or potentially from terrorist incident.

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