CBRNE – Vomiting Agents – Dm, Da, Dc

CBRNE – Vomiting Agents – Dm, Da, Dc

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The chemical warfare agents diphenylchlorarsine (Da), diphenylcyanoarsine (Dc), and diphenylaminearsine (Dm, adamsite) belong to a group of chemicals 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.

The synthesis of these agents dates back to the early 20th century. In 1915, Wieland, a German chemist, synthesized the agent Dm. Three years later, a US chemist, Robert Adams, independently developed this same compound and named it adamsite. Since that time, these agents have been produced for two purposes: as riot-control agents and as emesis-inducing agents to promote removal of personal protective gear during chemical warfare.

After World War II, large quantities of chemical weapons were disposed of at various dumping sites in Europe and Japan. Concerns have arisen regarding the potential environmental impact from contamination at these dumping locations.

Vomiting agents typically are disseminated as aerosols. The primary route of absorption is through the respiratory system. Exposure also can occur by ingestion, dermal absorption, or eye impact.

The effects of the vomiting agents by any route of exposure are slower in onset and longer in duration than typical riot control agents (eg, tear gas [CS]). On initial exposure, vomiting agents are irritants. This irritation is delayed for several minutes after contact. As a result of this delay, less early warning properties are present 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.

Recently, 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 were dumped into the Baltic Sea during the disarmament of Germany following WWII, and have resulted in extensive environmental contamination. [1, 2, 3, 4, 5] Because the agents Da, Dc, and Dm are arsenic-containing compounds, this has raised concern regarding the potential for long-term environmental toxicity from contamination of sea water, sediment, and fish. No significant human illness has been reported from this region.

However, a recent 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. [6]  Central nervous system damage 3 years after cessation of exposure to DPA appears to be persistent. [7] 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. [8] Further study is needed to better assess the health risks of exposure to water contaminated with DPA.

United States

The use of vomiting agents within the United States against civilians has never been reported. 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. Da was not well filtered by the standard-issue gas masks at that time. It resulted in nausea and vomiting, causing enemy troops to remove their masks. This rendered those personnel vulnerable to the toxic effects of other agents such as 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 a 45-year-old 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.

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.

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. [6] These signs and symptoms improved when the patient was no longer exposed to the contaminated water.

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Sanderson H, Fauser P, Thomsen M, Larsen JB. Weight-of-evidence environmental risk assessment of dumped chemical weapons after WWII along the Nord-Stream gas pipeline in the Bornholm Deep. J Hazard Mater. 2012 May 15. 215-216:217-26. [Medline].

Sanderson H, Fauser P, Rahbek M, Larsen JB. Review of environmental exposure concentrations of chemical warfare agent residues and associated the fish community risk following the construction and completion of the Nord Stream gas pipeline between Russia and Germany. J Hazard Mater. 2014 Aug 30. 279:518-26. [Medline].

Sanderson H, Fauser P, Thomsen M, Sørensen PB. Human health risk screening due to consumption of fish contaminated with chemical warfare agents in the Baltic Sea. J Hazard Mater. 2009 Feb 15. 162(1):416-22. [Medline].

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Christopher P Holstege, MD Professor of Emergency Medicine and Pediatrics, University of Virginia School of Medicine; Chief, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Center

Christopher P Holstege, MD is a member of the following medical societies: American Academy of Clinical Toxicology, Medical Society of Virginia, Society of Toxicology, Wilderness Medical Society, European Association of Poisons Centres and Clinical Toxicologists, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

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

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.

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 – Vomiting Agents – Dm, Da, Dc

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