- Author: Paul P Rega, MD, FACEP; Chief Editor: Zygmunt F Dembek, PhD, MPH, MS, LHD more...
Diphosgene (DP, trichloromethylchloroformate) 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 is described not only as a respiratory irritant but also as a lacrimator. The lacrimatory effect makes diphosgene more easily detected than phosgene (CG). 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 Germans staged the first major successful chemical attack of the war using chlorine. Chlorine then was replaced by phosgene, which caused greater casualties. Gas masks of the era were designed to filter out phosgene. Diphosgene was created by combining phosgene with chloroform, which destroyed the gas filters, and it was first utilized in the field in May 1916. Blistering and nerve agents largely have replaced the pulmonary agents chlorine, phosgene, and diphosgene.
In the field, diphosgene (DP) 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/cubic meter for 50% of exposed resting adults. Clinically, DP 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. DP 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 DP 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.
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. Diphosgene must be transported in glass (instead of 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.
As with phosgene, the principal feature of diphosgene (DP) 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, patients often inhale significant amounts of vapor before symptoms appear.
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