Phosgene

Endpoint summary

Description of key information

Phosgene is very toxic by inhalation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

8.6 mg/m³

Quality of whole database:

The study is GLP compliant and of high quality (Klimisch score=1)

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No animal studies on acute oral or dermal toxicity of phosgene are available. Since phosgene is a gas at room temperature and phosgene in aqueous environment rapidly hydrolyses to carbon dioxide and hydrochloric acid, exposure by the oral or dermal route is highly unlikely. The half-life in water has been estimated at 0.026 seconds (Manogue and Pigford , A.I.Ch.E. Journal 6(3): 494-500 (1960)).

An acute inhalation toxicity test in rats with phosgene gas (nose-only) according to OECD TG 403 revealed median lethal concentrations (LC50) and estimated non-lethal threshold concentrations (LC01) for 10, 30, 60 and 240 minutes of 253.3 (105.3), 54.5 (29.2), 31.3 (21.1), and 8.6 (5.3) mg/m3, respectively (Pauluhn, 2006a). The corresponding Cn x t products were 2532, 1635, 1878, and 2052 mg/m3 x min. In this range of exposure durations, the exponent n was found to be ≈ 0.9 for both median lethal (LC50) as well as the lethal threshold (LC01) effects. The ratios of LC50/LC01 were 2.4, 1.9, 1.5, and 1.6 for 10, 30, 60, and 240 minutes, respectively. Due to the apparent rat-specific changes in breathing patterns at very short durations of exposure, a generic ratio of 1.5 appears to be most representative. In all exposure groups of both sexes clinical signs of the respiratory tract (mainly bradypnea, labored breathing patterns, irregular breathing patterns, stridor, breathing sounds, nasal discharge (serous) and salivation) were observed after phosgene exposure. Statistically significant and concentration-dependent effects of body weight gains were observed in all exposure groups. In all rats that succumbed during the course of study an increased incidence of macroscopic alterations of the respiratory tract were found. These were characterized by a white foamy discharge from the nose, a less collapsed and discolorated (mainly dark-red) lung, hydrothorax, and trachea with white foamy content. Surviving rats did not show macroscopic alterations considered to be of pathodiagnostic significance. In summary, the inhalation LC50 in rats of both sexes was determined to be 8.6 mg/m3 for 4 hours of exposure to phosgene gas. The analysis of the C × t dependent mortality revealed a steep C × t mortality relationship. The various C x t products appear to follow Haber's rule, although departures may occur at high-level short-term exposures due to apparent rodent-specific irritant related changes in breathing patterns.

In a further acute inhalation study in male rats LC0 values of 15.36 and 1.57 mg/m3 were determined after 30- and 240 min exposure (nose-only) to phosgene gas (Pauluhn, 2006b). The corresponding C x t products of 461 (30 min) and 376 (240 min) mg/m3 x min provided evidence of a transient impairment of the alveolar blood-air barrier; however, which did not lead to any long-term changes of lung tissue.

In an acute inhalation study in male and female Beagle dogs no animal died after a single 30 min exposure (head-only) to 35 mg/m3 phosgene gas (Pauluhn, 2006c). At this test concentration an intraalveolar edema with some evidence of an adversely affected gas exchange was observed. The corresponding C x t product was 1050 mg/m3 x min.

For evaluation of acute inhalation toxicity see also chapter 7.9.3 "Endpoint summary: Mechanism of action (inhalation toxicity)" where the outcome of the acute toxicity studies in rats (Pauluhn, 2006b) and dogs (Pauluhn, 2006c) were discussed with regard to the derivation of an occupational exposure limit (MAK value; EU SCOEL).

Justification for selection of acute toxicity – inhalation endpoint
Only one key study with a 4h LC50 value available

Justification for classification or non-classification

Classified according to Annex I of Directive 67/548/EEC with R26 (very toxic by inhalation) and according to Annex VI of Regulation (EC) No 1272/2008 with Acute Tox Cat.1 (H330: Fatal if inhaled).