Practice Essentials
The chemical warfare agents diphenylchlorarsine (Da, Clark 1), diphenylcyanoarsine (Dc, Clark 2), and diphenylaminechlorarsine (Dm, adamsite) are classified as vomiting agents. Da appears as colorless crystals, Dc as a white solid, and Dm as light yellow-to-green crystals. Da and Dm are odorless, and Dc reportedly has an odor similar to garlic or bitter almonds. All three agents are insoluble in water.
Dm is the most toxic agent of this group, with an estimated LCt50 of 11,000 mg·min/m3 (ie, an estimated 50% lethality for a group of patients breathing air with a concentration of 11,000 mg/m3 for 1 min). Other factors also are important, such as the exposed patient's preexisting health status and the time from exposure to medical care. The dose at which vomiting reportedly begins for Dm is estimated as 370 mg·min/m3.
The initial care of patients exposed to vomiting agents primarily is supportive. No specific antidotes are available. Fewer than 1% of those exposed to diphenylaminechlorarsine (Dm, adamsite) will have severe or prolonged effects warranting medical care. Focus care on relieving irritant and systemic effects.
Health care facilities may be overwhelmed quickly if a large-scale exposure occurs with multiple casualties.
and appropriate transfer of patients to less stressed facilities may be necessary.
For patient education resources, see the Biological Warfare, as well as Chemical Warfare and Personal Protective Equipment.
Background
The synthesis of these agents dates back to the early 20th century. In 1915, Wieland, a German chemist involved in weapons research, synthesized the agent Dm. Three years later, a US chemist, Robert Adams, independently developed this same compound and named it adamsite. These agents have since been produced for two purposes: as riot-control agents and as emesis-inducing agents to promote removal of personal protective gear, thereby increasing susceptibility to subsequent chemical warfare agent exposure.
After World War II, large quantities of chemical weapons, including vomiting agents, were disposed of at various dumping sites in Europe and Japan. The majority of dumping sites are located at sea, since this strategy was deemed more cost effective and facile than land storage or incineration. [1] However, ocean currents and human activity, such as fishing, have disturbed these deposits. Though chemical warfare agent disposal at sea has since been outlawed, concerns remain regarding the potential environmental impact from contamination at previous dumping locations.
Pathophysiology
Vomiting agents typically are disseminated as aerosols. Therefore, the primary route of absorption is through the respiratory system, but exposure also can occur by ingestion, dermal absorption, or eye impact.
Regardless of the route of exposure, the onset of the effects of the vomiting agents are slower in onset and longer in duration than typical riot control agents (eg, tear gas [CS]). [2, 3] On initial exposure, vomiting agents are irritants. This irritation is delayed for several minutes after contact, resulting in less early warning properties for those exposed. By the time symptoms of irritation occur and personnel consider donning their protective equipment, significant contamination already may have occurred.
Systemic signs and symptoms follow the initial irritation and consist of headache, nausea, vomiting, diarrhea, abdominal cramps, and mental status changes. Symptoms typically persist for several hours after exposure. Death has been reported with excessive exposure.
Concerns have arisen regarding the potential environmental and human health impact of chronic exposure to vomiting agents due to contamination at sites where these chemicals were dumped following WWII. Sanderson and colleagues have documented that approximately 11,000 tons of chemical warfare agents, including adamsite, were dumped into the Baltic Sea during the disarmament of Germany following WWII, and have resulted in extensive environmental contamination. [4, 5, 6, 7, 8, 9] Because the vomiting agents Da, Dc, and Dm contain arsenic, there is concern regarding potential long-term environmental toxicity from contamination of sea water and adsorption into sediment. There is a signficant risk of bioaccumulation into fish. No significant human illness has been reported from this region.
It has been reported that Dm (adamsite) is oxidized, methylated, and glutathione (GSH) conjugated by the enzymes in the cod liver, although the impact of these metabolites on human health are unknown. [10] A study of acute toxicity of organoarsenic chemical warfare agents found that Da and Dm were lethal to fish embryos and represent an environmental threat to the recovery of the Baltic population of a number of species. [11]
However, a case series from Japan describes a syndrome of cerebellar symptoms including tremors, myoclonus, memory impairment, and sleep disturbances associated with consumption of well water contaminated with diphenylarsinic acid (DPA), a byproduct from the degradation of diphenylchloroarsine or diphenylcyanoarsine. [12] Central nervous system damage 3 years after cessation of exposure to DPA appears to be persistent. [13] Other investigators from Japan have attempted to study the effect of DPA in mice and have discovered the possibility for injury to Purkinje cells due to oxidative and nitrosative stress following exposure to DPA, which may lead to cerebellar symptoms. [14]
After performing a number of studies of diphenylarsinic acid (DPA) in drinking water in mice and rats, Yamaguchi and colleagues concluded that the effects of chronic exposure to DPA is likely restricted to the central nervous system and that DPA is not carcinogenic in humans. [15, 16, 17]
Etiology
Human exposures to vomiting agents rarely have been reported. Potential causes of exposure to these agents are laboratory accidents, terrorist events, or military conflicts.
Epidemiology
Frequency
United States
There are no reported instances of the use of vomiting agents within the United States against civilians. In 1932, adamsite was suspected to have been laced into riot control gas deployed in Washington D.C. against the Bonus Army, which was composed of World War I veterans, civilian members of their families, and affiliated groups, who were demanding financial compensation for their service certificates.
Currently, the US government is funding numerous programs to prepare the nation for potential chemical terrorist attacks against its citizens and military.
International
The use of vomiting agents has been reported during international conflicts. Da first was used by German troops in 1917. Since Da was not well filtered by the standard-issue gas masks at that time, troops inhaled Da and experienced nausea and vomiting. As a result of emesis, soldiers removed their gas masks, which made them vulnerable to subsequent attacks with other highly toxic chemical warfare agents, including phosgene and chlorine gas. The Germans also produced Dc and Dm, but limited documentation exists for use of these agents during World War I. Questionable reports exist of vomiting agents used in other countries as riot control agents.
In June 2003, letters containing Dm (adamsite) were sent to the United States, British, and Saudi Arabian Embassies, Belgium’s prime minister Guy Verhofstadt, the Court of Brussels, a Belgian ministry, the Oostende airport, and the Antwerp port authority. At least two postal workers and five police officers were hospitalized with symptoms of skin irritation, eye irritation, and breathing difficultly after exposure to the substance. Three people who were exposed in Oostende were also hospitalized. Belgium police suspected an Iraqi political refugee opposed to the US Iraq War. Upon searching his residence, antiterrorism investigators found a plastic bag containing powder. The investigators suffered symptoms similar to those who were exposed to the letters, and the Iraqi was charged with premeditated assault.
No other instances of vomiting agent use have been reported, although buried adamsite has been found in one of many chemical weapons dumping sites in Shikhany, Russia. North Korea has been suspected of synthesizing and stockpiling adamsite (DM) at its Aoji-ri chemical complex.
A review of 292 terrorist attacks using chemical agents between 1970 and 2019 found that Dm (adamsite) was the primary agent in 7 attacks. [18]
Race-, sex-, and age-related demographics
No published studies demonstrate a significant difference in the effects of vomiting agents on various races or either sex. Intuitively, persons at the extremes of age would be less tolerant of exposure to these three chemical agents. However, no published studies prove this.
In a case series from Japan describing cerebellar symptoms associated with drinking well water contaminated with diphenylarsinic acid (DPA), a degradation product of diphenylchloroarsine or diphenylcyanoarsine, an infant presented with cognitive impairment and developmental delay with mild cerebral atrophy documented by magnetic resonance imaging. [12] These signs and symptoms improved when the patient was no longer exposed to the contaminated water.
Prognosis
The prognosis is good for persons exposed to vomiting agents if they do not develop secondary injuries. Full recovery is expected in most patients.
Complications are expected to be rare in persons exposed to vomiting agents if rapid and adequate supportive care is initiated. Exceptions are as follows:
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If significant ocular exposure occurs, corneal chemical burns may develop
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In persons with preexisting lung disease, exacerbation of the lung disease may occur
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If a patient sustains a large exposure, coma may develop, with subsequent risk of anoxic brain injury and aspiration pneumonia
Corneal chemical burns
Significant exposure to vomiting agents can lead to damage of the cornea. If the patient complains of significant eye discomfort, foreign body sensation, photophobia, or decreased visual acuity, consider eye irrigation. Thoroughly examine the eye and include visual acuity testing. Perform slit lamp examination with fluorescein. If a chemical corneal burn is documented, a cycloplegic may be used to reduce pain; apply topical antibiotic ointment. Arrange follow-up care with an ophthalmologist within 24 hours. For more information, see Ocular Burns.
Acute bronchospasm
As with many types of chemical inhalation exposures, acute bronchospasm may develop in patients exposed to vomiting agents. This is especially true of patients with preexisting lung disease (eg, asthma). If acute bronchospasm occurs leading to respiratory distress, treatment with bronchodilators (eg, albuterol) may be necessary.
Anoxic brain injury
If an exposed person becomes comatose and loses the ability to maintain ventilatory function, hypoxia may develop, leading to anoxic brain injury. However, this complication is exceedingly rare except after massive exposure to vomiting agents.
Inability of exposed patients to maintain their airway may result in aspiration of gastric contents into the lungs, causing aspiration pneumonia
