Diphosgene Exposure

Updated: Sep 19, 2023
Author: Paul P Rega, MD, FACEP; Chief Editor: Zygmunt F Dembek, PhD, MS, MPH, LHD 


Practice Essentials

Diphosgene (DP, trichloromethylchloroformate), which was created by combining phosgene with chloroform, was a product of the chemical weapons race in World War I. It belongs to a class of chemicals termed lung-damaging agents or choking agents.These agents attack lung tissue directly, causing pulmonary edema. Diphosgene also produces lacrimation, and so is more easily detected than phosgene. The mechanism of action is not well understood, but the chemical is believed to react directly upon the alveolar and capillary walls. The production of leukotrienes and the excessive accumulation of neutrophils may affect the alveolar sites sufficiently to cause pulmonary edema.

The first major successful chemical attack of World War I, which was staged by the Germans, used chlorine. Chlorine then was replaced by phosgene, which caused greater casualties. Gas masks of the era were designed to filter out phosgene. Diphosgene destroyed the gas filters, and it was first utilized in the field in May 1916. Blistering and nerve agents largely replaced the pulmonary agents chlorine, phosgene, and diphosgene.

In the field, diphosgene rapidly vaporizes and breaks down into phosgene and chloroform. It is a colorless gas under standard temperatures and pressures, but it can also be found as an oily, colorless liquid. It emits an odor reminiscent of green corn or new-mown hay. Its lethal dose is 3000 mg/min/mm3 for 50% of exposed resting adults.

Clinically, diphosgene behaves in essentially the same manner as phosgene. The chloroform does not reach levels sufficient to cause toxicity, even of the liver, during tactical employment. Diphosgene is heavier than air and remains in low-lying areas for longer periods. Therefore, children are at increased risk for a greater absorption of the agent. Doses are cumulative, since diphosgene is not detoxified in the body. Symptoms may be delayed for more than 3 hours after exposure with minimal contact, but in the presence of high concentrations the effects will be immediate, especially with its strong lacrimator action.[1]

Diphosgene deployment almost surely indicates a purposeful, not an accidental, event. Industrial accidents have occurred with both chlorine and phosgene but not with diphosgene, which is not a normal product of manufacturing processes. It also is relatively unstable and degrades easily into phosgene and chloroform.[2]  Diphosgene must be transported in glass (not metal) containers.

Research is ongoing with regard to developing a sensitive, cost-effective, easy-to-use environmental sensing instrument that could detect a diphosgene release efficaciously. One device that shows promise is a high-resolution proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOFMS) instrument.[3, 4]  

The use of tubes packed with pellets made of magnesium aluminum metasilicate treated with a suitable monoterpene (camphor, menthol) to increase porosity and specific surface area has been shown to detect diphosgene at a concentration of only 0.1 mg/m3 in the air.[5, 6]


As with phosgene, the principal feature of diphosgene (DP) exposure is delayed pulmonary edema. Although the mechanism is not entirely clear, edema may be caused by direct alveolar damage when diphosgene breaks down into hydrochloric acid and carbon dioxide in the presence of water. DP also causes irritation of the upper respiratory tract and rarely can cause airway obstruction. Respiratory effects occur at doses of 1-10 ppm. Doses greater than 25 ppm can be rapidly fatal.

Toxicity varies with both the concentration of vapor and the length of exposure. Because of the low water solubility of diphosgene, exposed persons often inhale significant amounts of vapor before developing symptoms.

DP vapor is heavier than air. It decomposes on heating and produces toxic and corrosive fumes including chlorine and phosgene. DP also reacts with water to produce toxic and corrosive fumes.[7]

Patient Education

Alert patients who have experienced possible diphosgene exposure that they should return to the emergency department or contact 911 if they develop respiratory changes, such coughing, wheezing, or shortness of breath. For patient education information, see Biological and Chemical Weapons.




Victims of diphosgene (DP) exposure likely will have been involved in a mass gathering or military event within the last 24 hours that resulted in mass casualties with respiratory complaints. Patients may report explosions, smoke, or a gas cloud. Patients inconsistently report the odor of newly mown hay.

Presenting complaints may include the following:

  • Patients report irritation of the eyes or the skin.
  • Exposure to low concentrations of DP tends to cause lacrimation and irritation of the eyes and skin.
  • Exposure to somewhat higher concentrations causes chest discomfort and dyspnea; pulmonary edema often does not manifest until a few hours have passed, and the symptoms are aggravated by physical effort [7]
  • Exposure to high concentrations can quickly cause pulmonary edema with cough, dyspnea, and production of frothy sputum. Signs include tachypnea, rales, and decreased oxygen saturations.
  • Further cardiopulmonary decompensation can occur from noncardiogenic pulmonary edema, with respiratory failure, hypotension, and death.
  • Direct eye exposure to diphosgene liquid can cause corneal abrasions, ulcers, or perforation. Direct skin exposure to diphosgene liquid can cause burns.

Physical Examination

Physical findings include the following:

  • Lacrimation and irritation of the eyes and skin - Direct eye exposure to diphosgene (DP) liquid can cause corneal abrasions, ulcers, or perforation.
  • Direct skin exposure to diphosgene liquid can cause burns.
  • Chest discomfort
  • Tachycardia
  • Tachypnea
  • Dyspnea
  • Frothy sputum
  • Cough
  • Wheezing
  • Noncardiogenic pulmonary edema (decreased oxygen saturation)
  • Respiratory failure
  • Hypotension


Diagnostic Considerations

Noncardiogenic pulmonary edema due to diphosgene (DP) must be distinguished from noncardiogenic pulmonary edema due to other causes. Features in the history that suggest DP include the following:

  • Mass casualties
  • A terrorist or military attack
  • Gas exposure
  • Delayed onset of pulmonary edema following symptom onset

Differential Diagnoses



Approach Considerations

No laboratory test confirms diphosgene (DP) exposure. Arterial blood gas measurement may be useful to determine the degree of hypoxemia or acidemia in patients who are being considered for endotracheal tube placement.

Chest radiographs may initially appear normal but eventually reveal pulmonary edema in patients with significant exposure. Because of the possibility of delayed pulmonary edema, a baseline chest radiograph should be considered prior to discharge.

An electrocardiogram can be obtained to help ensure that the patient does not have cardiogenic pulmonary edema or stress-induced ischemia.




Prehospital Care

Scene responders need to ensure their own safety when possible to prevent becoming victims themselves. Remove patients from the scene and move them to fresh air or administer oxygen if necessary. Terminate exposure by removing patients' clothing. Begin skin decontamination with soap and water. Pulmonary edema may be precipitated by exertion. Enforce strict bedrest if possible.



Emergency Department Care

Management is supportive and no antidote exists. Begin or continue care as discussed in Prehospital Care above. Minimize exertion on the part of the patient so as to lessen the risk of delayed pulmonary edema.

Administer standard resuscitation measures. Patients can present with airway obstruction, although that is rare. Acute pulmonary edema is common, and patients may require positive end-expiratory pressure if they are clinically in respiratory distress or frank failure. Avoid use of diuretics. Patients also can present with hypotension; perform standard resuscitation with crystalloid fluids as first-line agents and vasopressors as second-line agents.

Give bronchodilators to patients with bronchospasm. Systemic steroids likely are not beneficial routinely for diphosgene exposure, except in patients with bronchospasm not controlled by bronchodilators. Some literature suggests using inhalational steroids for phosgene poisoning, which may lessen the severity of pulmonary edema. Similar regimens possibly may be used for diphosgene inhalation. However, treatment should be initiated within a short time of exposure (15 min). One regimen uses dexamethasone and another uses betamethasone or beclomethasone in doses higher than that prescribed for asthma therapy.

Eyes should be copiously irrigated with standard solutions and then assessed for visual acuity and corneal damage.

Contact with liquid diphosgene may produce chemical burns. After thorough decontamination, these may be treated with standard burn therapy.

Antibiotics are unnecessary, prophylactically or therapeutically, unless a secondary infection is present.

Admit patients who require resuscitation or oxygen supplementation. For at least 12 hours, observe patients with likely diphosgene exposure who have minor symptoms or are asymptomatic, since delayed pulmonary edema is the classic feature of diphosgene exposure. However, one reference suggests that a minimum of 6 hours of observation is sufficient for a phosgene exposure.[1]

Counsel all patients with significant exposure to avoid strenuous activities for 72 hours and to return if significant respiratory symptoms develop.


Consult an ophthalmologist for a significant eye injury and a pulmonologist in the event of significant respiratory exposure.



Medication Summary

In general, follow decontamination with soap and water by symptomatic treatment.


Class Summary

This agent is used to relieve significant bronchospasm.

Albuterol 0.5% (Proventil, Ventolin)

Used to relieve bronchospasm after diphosgene (DP) exposure. Beta-agonist for bronchospasm refractory to epinephrine. Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility.