Acute nose-only inhalation exposure of rats to di- and triphosgene relative to phosgene

Abstract

Groups of young adult Wistar rats were acutely exposed to trichloromethyl chloroformate (diphosgene) and bis(trichloromethyl) carbonate (triphosgene) vapor atmospheres using a directed-flow nose-only mode of exposure. The exposure duration used was 240 min. The median lethal concentration (LC₅₀) of diphosgene and triphosgene was 13.9 and 41.5 mg/m³, respectively. Based on the molar exposure concentrations, the LC₅₀s of phosgene (previously published), diphosgene, and triphosgene were 0.07, 0.07, and 0.14 mmol/m³, respectively. Although the principal toxic mode of action of the volatile diphosgene was similar to phosgene gas, the vapor phase of triphosgene appeared to be different to that of phosgene and diphosgene based on a more persistent occurrence of signs of respiratory distress and a biphasic onset of mortality. While all substances caused mortality within 1 day postexposure, triphosgene induced a second phase of mortality 11–14 days postexposure. The vapor saturation concentration of triphosgene at ambient temperature is ≈100 times its LC₅₀. In summary, triphosgene-induced lung injury patterns are different from that of phosgene and diphosgene. More research is needed to close the substantial data gaps of triphosgene.

Keywords::

• Nose-only inhalation
• mode of action
• delayed mortality

Acknowledgement

The author thanks A. Thiel for excellent technical assistance and Dr. A. Folkerts for the analytical characterization of exposure atmospheres.

Declaration of interest

This study was performed on behalf of Bayer AG. The conclusions of study are those of the author.