eMedicine Specialties > Emergency Medicine > Warfare - Chemical, Biological, Radiological, Nuclear and Explosives

CBRNE - Vomiting Agents - Dm, Da, Dc

Author: Christopher P Holstege, MD, Associate Professor of Emergency Medicine and Pediatrics, University of Virginia; Director, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Ctr, Associate Medical Toxicology Fellowship Director, VA Dept of Health
Coauthor(s): Jennifer S Boyle, MD, PharmD, Fellow in Toxicology, University of Virginia Health System
Contributor Information and Disclosures

Updated: Mar 16, 2010

Introduction

Background

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 3 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 2 purposes, as riot-control agents and as emesis-inducing agents to promote removal of personal protective gear during chemical warfare.

Following WWII, large quantities of chemical weapons were disposed of at various dumping sites in Europe and Japan. Recently, new concerns have arisen regarding the potential environmental impact from contamination at these dumping locations.

Pathophysiology

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, 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 subsequently 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. According to a recent article by Sanderson et al published in the Journal of Hazardous Materials, approximately 11,000 tons of chemical warfare agents were dumped into the Baltic Sea during the disarmament of Germany following WWII.¹ 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.² 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.³ Further study is needed to better assess the health risks of exposure to water contaminated with DPA.

Frequency

United States

The use of vomiting agents within the United States against civilians never has 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. No recent use of vomiting agents is documented.

Mortality/Morbidity

DM is the most toxic agent of this group, with an estimated LCt50 of 11,000 mg·min/m³ (eg, 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.

Race

No published studies demonstrate a significant difference in effects of vomiting agents on various races.

Sex

No published studies demonstrate a significant difference in effects of vomiting agents by gender.

Age

Intuitively, those at the extremes of age would be less tolerant of exposure to these 3 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 MR imaging.² These symptoms improved when the patient was no longer exposed to the contaminated water.

Clinical

History

• A history of exposure to an aerosolized substance that resulted in ophthalmic and pulmonary irritation and then progressed to nausea, vomiting, abdominal cramps, and headache suggests exposure to a vomiting agent.
• In the early phases of an emergency response, the toxin's identification would be unknown and the history misleading and inaccurate.
  • Fear, anxiety, and mistrust are likely to affect victims, emergency responders, bystanders, and the entire community after such an incident.
  • Overwhelming emotions in some patients, rescuers, and hospital staff are likely to cause acute anxiety reactions and mass psychogenic illness. Patients truly suffering from vomiting-agent poisoning and those suffering from mass psychogenic illness would be difficult to separate, because the symptoms are similar. Patients with either condition may complain of nausea, vomiting, diarrhea, headache, tearing, dizziness, chest tightness, and shortness of breath.
  • Because differentiating mass hysteria from a true vomiting-agent poisoning may be difficult, treat all patients experiencing symptoms as true toxic emergencies. The potential exists for patients with mass psychogenic illness to overwhelm the entire emergency response system and hinder timely treatment of those with true toxic emergencies.

Physical

The signs and symptoms encountered in a person exposed to a vomiting agent may vary. Factors that determine clinical effects include the amount of the agent encountered and the route of exposure. Depending on these variables, the progression of signs and symptoms can range from mild mucosal irritation to cardiovascular collapse and death. The following list constitutes findings that may be noted on physical examination following exposure to vomiting agents:

• Eye - Conjunctival injection, tearing, and blepharospasm
• Nose - Excessive nasal discharge, sneezing, mucosal injection, and edema
• Throat - Mucosal injection and edema
• Lungs - Excessive cough, wheezing, rhonchi, prolonged expiratory phase, and tachypnea
• Heart - Tachycardia
• Abdomen - Hyperactive bowel sounds, intestinal cramps, emesis, and diarrhea
• Skin - Erythema and edema at the site of dermal contact
• Mental status - Central nervous system depression, syncope, and death (possible with significant exposure)

Causes

Human exposures to vomiting agents rarely have been reported. Potential causes of exposure to these agents are laboratory accidents, terrorist events, or military conflicts.

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