lewisite

Lewisite (L) (A-243) is an organoarsenic compound. It was once manufactured in the U.S., Japan, Germany and the Soviet Union for use as a chemical weapon, acting as a vesicant (blister agent) and lung irritant. Although the substance is colorless and odorless in its pure form, impure samples of lewisite are a yellow, brown, violet-black, green, or amber oily liquid with a distinctive odor that has been described as similar to geraniums.

Chemical reactions

The compound is prepared by the addition of arsenic trichloride to acetylene in the presence of a suitable catalyst:
:AsCl₃ + C₂H₂ → ClCHCHAsCl₂ (Lewisite)
Lewisite, like other arsenous chlorides, hydrolyses in water to form hydrochloric acid and chlorovinylarsenous oxide (a less-powerful blister agent):
:ClCHCHAsCl₂ + 2 H₂O → ClCHCHAs(OH)₂ + 2 HCl
This reaction is accelerated in alkaline solutions, and forms acetylene and trisodium arsenate.

Lewisite reacts with metals to form hydrogen gas. It is combustible, but difficult to ignite.

Mechanism of action

Lewisite is a suicide inhibitor of the E3 component of pyruvate dehydrogenase. As an efficient method to produce ATP, pyruvate dehydrogenase is involved in the conversion of pyruvate to acetyl-CoA. The latter subsequently enters the TCA cycle. Peripheral nervous system pathology usually arises from Lewisite exposure as the nervous system essentially relies on glucose as its only catabolic fuel.

It can easily penetrate ordinary clothing and latex rubber gloves. Upon skin contact it causes immediate stinging, burning pain and itching that can last for 24 hours. Within minutes, a rash develops and the agent is absorbed through the skin. Large, fluid-filled blisters (similar to those caused by mustard gas exposure) develop after approximately 12 hours and cause pain for 2–3 days. These are severe chemical burns and begin with small blisters in the red areas of the skin within 2–3 hours and grow worse, encompassing the entire red area, for the ensuing 12–18 hours after initial exposure. Liquid lewisite has faster effects than lewisite vapor. Sufficient absorption can cause deadly liver necrosis.

Those exposed to lewisite can develop refractory hypotension (low blood pressure) known as Lewisite shock, with some features of arsenic toxicity. Lewisite damages capillaries, which then become leaky, reducing blood volume required to maintain blood pressure, a condition called hypovolemia. When the blood pressure is low, the kidneys may not receive enough oxygen and can be damaged.

Inhalation, the most common route of exposure, causes burning pain and irritation throughout the respiratory tract, nosebleed (epistaxis), laryngitis, sneezing, coughing, vomiting, difficult breathing (dyspnea), and in severe cases of exposure, can cause fatal pulmonary edema, pneumonitis, or respiratory failure. Ingestion results in severe pain, nausea, vomiting, and tissue damage. The results of eye exposure can range from stinging, burning pain and strong irritation to blistering and scarring of the cornea, along with blepharospasm, lacrimation, and edema of the eyelids and periorbital area. The eyes can swell shut, which can keep the eyes safe from further exposure. The most severe consequences of eye exposure to lewisite are globe perforation and blindness. Generalised symptoms also include restlessness, weakness, hypothermia and low blood pressure.

It is possible that Lewisite is carcinogenic: arsenic is categorized as a respiratory carcinogen by the International Agency for Research on Cancer, though it has not been confirmed that lewisite is a carcinogen.

Lewisite causes damage to the respiratory tract at levels lower than the odor detection threshold. Early tissue damage causes pain.

Hydrolysis leads to chlorovinylarsonous acid, CVAA.

Treatment

British anti-lewisite, also called dimercaprol, is the antidote for lewisite. It can be injected to prevent systemic toxicity, but will not prevent injury to the skin, eyes, or mucous membranes. Chemically, dimercaprol binds to the arsenic in lewisite. It is contraindicated in those with peanut allergies.

Other treatment for lewisite exposure is primarily supportive. First aid of lewisite exposure consists of decontamination and irrigation of any areas that have been exposed. Other measures can be used as necessary, such as airway management, assisted ventilation, and monitoring of vital signs. In an advanced care setting, supportive care can include fluid and electrolyte replacement. Because the tube may injure or perforate the esophagus, gastric lavage is contraindicated.

Long-term effects

From one acute exposure, someone who has inhaled lewisite can develop chronic respiratory disease; eye exposure to lewisite can cause permanent visual impairment or blindness.

Chronic exposure to lewisite can cause arsenic poisoning (due to its arsenic content) and development of a lewisite allergy. It can also cause long-term illnesses or permanent damage to organs, depending on where the exposure has occurred, including conjunctivitis, aversion to light (photophobia), visual impairment, double vision (diplopia), tearing (lacrimation), dry mucous membranes, garlic breath, burning pain in the nose and mouth, toxic encephalopathy, peripheral neuropathy, seizures, nausea, vomiting, chronic obstructive pulmonary disease (COPD), bronchitis, dermatitis, skin ulcers, basal cell carcinoma, and squamous cell carcinoma.

Chemical composition

Lewisite can be a mixture of molecules with a different number of vinylchloride groups on the arsenic chloride: lewisite itself (2-chlorovinylarsonous dichloride), along with ''bis''(2-chlorovinyl)arsinous chloride (lewisite 2) and ''tris''(2-chlorovinyl)arsine (lewisite 3). In addition, there are sometimes isomeric impurities: lewisite itself is mostly ''trans''-2-chlorovinylarsonous dichloride, but the ''cis'' stereoisomer and the constitutional isomer (1-chlorovinylarsonous dichloride) may also be present.

Experimental and computational studies both find that the ''trans''-2-chloro isomer is the most stable, and that the carbon–arsenic bond has a conformation in which the lone pair on the arsenic is approximately aligned with the vinyl group.

History

Lewisite was synthesized in 1904 by Julius Arthur Nieuwland during studies for his PhD. In his thesis, he described a reaction between acetylene and arsenic trichloride, which led to the formation of lewisite. Exposure to the resulting compound made Nieuwland so ill he was hospitalized for several days.

Lewisite is named after the US chemist and soldier Winford Lee Lewis (1878–1943). In 1918, John Griffin, Julius Arthur Nieuwland's thesis advisor, drew Lewis's attention to Nieuwland's thesis at Maloney Hall, a chemical laboratory at The Catholic University of America, Washington D.C. Lewis then attempted to purify the compound through distillation but found that the mixture exploded on heating until it was washed with HCl.

Lewisite was developed into a secret weapon at a facility located in Cleveland, Ohio (The Cleveland Plant) at East 131st Street and Taft Avenue, and given the name "G-34", which had previously been the code for mustard gas, in order to confuse its development with mustard gas. On November 1, 1918, production began at a plant in Willoughby, Ohio.
It was not used in World War I, but Britain experimented with it in the 1920s as the "Dew of Death".

After World War I, the US became interested in lewisite because it was not flammable. Up until World War II, it had the military symbol of "M1", after which it was changed to "L". Field trials with lewisite during World War II demonstrated that casualty concentrations were not achievable under high humidity, due to the rate of hydrolysis and the characteristic odor of the chemical, and lacrymation forced troops to don masks and avoid contaminated areas. The United States produced about 20,000 tons of lewisite, keeping it on hand primarily as an antifreeze for mustard gas, or to penetrate protective clothing in special situations.

Lewisite was replaced by the mustard gas variant HT (a 60:40 mixture of sulfur mustard and O-Mustard), and was declared obsolete in the 1950s. Lewisite poisoning can be treated effectively with British anti-lewisite ( dimercaprol). Most stockpiles of lewisite were neutralised with bleach and dumped into the Gulf of Mexico. Some remained at the Deseret Chemical Depot located outside Salt Lake City, Utah, but, as of January 18, 2012, all U.S stockpiles had been destroyed.

Production of quantities greater than 100 grams per year per facility were banned by Schedule 1 of the 1993 Chemical Weapons Convention. When the convention entered force in 1997, the parties declared world-wide stockpiles of 6,747 tonnes. By the end of 2015, 98% of the declared stockpiles had been destroyed.

In 2001, lewisite was found in a World War I weapons dump in Washington, D.C.

Controversy over Japanese deposits of lewisite in China

In mid-2006, China and Japan were negotiating disposal of lewisite stockpile in northeastern China, left by the Japanese military during World War II. People had died over the preceding twenty years from accidental exposure to these stockpiles.Abandoned Chemical Weapons (ACW) in China

See also

* Blue Cross (chemical warfare)

References

{{Authority control

Arsenical vesicants
Organoarsenic chlorides
Organochlorides
Alkene derivatives
Arsenic(III) compounds
World War I chemical weapons