Phosgene animal exposures

Developmental and reproductive toxicity studies regarding animal exposure to phosgene were not available. 

There are no controlled studies showing that any species of animal would make a good sentinel for phosgene oxime exposure. 

Most studies on the action of phosgene oxime have utilized animal studies. Human information has been obtained from accidental exposure to the chemical. Health effects following phosgene oxime exposure are dependent on the route of exposure. 

In their literature review, Diller and Zante (1982) also identified nonlethal effects from phosgene exposure (lethal effects are described in Section 2.1). Nonlethal information synthesized from this review is presented in Table 1-4. From the above data and from animal data for initial lung damage, Diller and Zante (1982) synthesized information for nonlethal effects of phosgene in humans (Table 1-5). 

Frosolono and Currie (1985) investigated the effect of phosgene on the pulmonary surfactant-system (PSS) in groups of six to 14 rats exposed to phosgene at 1 ppm for 4 h. The exposure system and parameters were similar to those described in Section 3.2.1 (Hatch et al. 1986). The actual chamber concentration was 1.0 0.06 ppm. Animals were sacrificed immediately after exposure, or on postexposure days 1, 2, or 3. Pulmonary edema was present immediately after exposure and persisted through day 3. Phosphatidylinositol levels were significantly (p<0.05) decreased compared with controls immediately after exposure only. Phosphatidylserine and phosphatidylethanolamine levels were significantly increased compared with controls on days 1, 2, and 3 postexposure. Phosphatidylcholine levels were increased at all time points compared with controls. 

In another study, Hartley guinea pigs (five per group) were exposed to phosgene at 0, 0.25, or 0.5 ppm for 4 h (Slade et al. 1989). The exposure chamber and atmosphere generation and measurement systems were similar to those used by Hatch et al. (1986). The LFP concentrations were measured 16 to 18 h after exposure. These investigators found that the LFP concentrations were elevated by 90% in animals exposed to phosgene at 0.25 ppm and 250% in animals exposed at 0.5 ppm, when compared with controls. 

Chasis, H. 1944. Phosgene Review of Literature on the effect of exposure in man and experimental animals. Contract W—49-036-CWS—1. 

As discussed in Section 2.3.3, the mechanism of chloroform-induced liver toxicity may involve metabolism to the reactive intermediate, phosgene, which binds to lipids and proteins of the endoplasmic reticulum, lipid peroxidation, or depletion of GSH by reactive intermediates. Because liver toxicity has been observed in humans exposed to chloroform levels as low as 2 ppm in the workplace and in several animal species after inhalation and oral exposure, it is possible that liver effects could occur in humans exposed to environmental levels, to levels in drinking water, or to levels found at hazardous waste sites. 

A method using micro-LC/tandem MS was developed for analysis of the tryptic digest containing the intramolecular albumin lysine-lysine adduct, which enabled the detection of exposure of human blood to > 1 xM phosgene in vitro. The method has not yet been applied to animal or human samples. 

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