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.

Attempts to counteract phosgene-induced acute lung injury by instant high-dose aerosol exposure to hexamethylenetetramine, cysteine or glutathione

“…However, as known from previous single, high-level inhalation studies, the ensuing ALI is rapidly repaired and long-term sequelae to high-level exposures exposure do not occur (Pauluhn, 2006b). The somewhat inconsistent observations reported in context with late-onset mortality responses in the range of 2 weeks post-exposure appear either be related to phosgene dissolved in a carrier substance or the use of triphosgene as the putative source of phosgene (Pauluhn, 2010). Figure 4.…”

“…Technical details of the validation and use of this inhalation chamber system have been published previously (Pauluhn, 2006a;Pauluhn and Thiel, 2007;Pauluhn, 2010). In brief, a controlled flow of phosgene were discharged from the cylinder into a continuous flows of conditioned dry air and then entrained into the plenum of a nose-only inhalation chamber (inhalation chamber dimensions: inner diameter = 14 cm, outer diameter = 35 cm (two-chamber system), height = 25 cm (internal volume = about 3.8 L).…”

Sensitive and Selective Detection of Phosgene, Diphosgene, and Triphosgene by a 3,4‐Diaminonaphthalimide in Solutions and the Gas Phase

“…1 Ha nd 13 CNMR spectra were measured in CDCl 3 with aB ruker AV spectrometer operating at 400 MHz and 100 MHz, respectively,a nd chemical shifts were reported in ppm by using tetramethylsilane (TMS) as the internal standard. 1 HNMR (400 MHz, CDCl 3 5-Amino-2-butyl-6-((2-ethoxyethyl)amino)-1 H-benzo[de]isoquinoline-1,3-(2 H)-dione (Phos-2) 2-Ethoxyethylamine (107 mg, 1.2 mmol) and triethylamine (152 mg, 1.5 mmol) were added into as olution of compound 1 [12] (377 mg, 1.0 mmol) in CH 3 CN (10 mL).…”

“…[1] On the otherh and, phosgenea nd diphosgene are highly toxic and were used as chemical warfare agents (CWAs) during World WarIand II. However,t riphosgene can cause more persistent respiratory distressa fter being breathed into the lungs [3] and easily converts into phosgene in the presence of tertiary amines. However,t riphosgene can cause more persistent respiratory distressa fter being breathed into the lungs [3] and easily converts into phosgene in the presence of tertiary amines.…”

Management of Phosgene-Induced Acute Lung Injury (ALI) by Personalized Protective PEEP-ECMO: What Can We Learn from Animal Bioassays?

“…The median lethal concentrations (LC50) following 4-hour exposure in rats was 7.2, 13.9, and 41.5 mg/m³ or 1.8, 1.7, and 3.4 ppm for phosgene, di-and triphosgene, respectively. Unlike the acute lung edema-driven mortality patterns observed in phosgene-and diphosgene-exposed rats, triphosgene caused additional delayed mortality patterns [2,3]. Hence, treatment strategies need to be guided by detailed information on the major irritants involved and the 'exposure dose'.…”