Chemical pneumonia was observed in rats exposed to phosgene at 2.0 ppm for 90 min (Gross et al. 1965). Biochemical markers of phosgene exposure, such as increased LFP, were observed in mice, rats, guinea pigs, hamsters, and rabbits exposed at up to 1 ppm for 4 h (Hatch et al. 1986; Diller et al. 1985). Other effects defined by AEGL-2 included “very ill” monkeys with labored breathing (Cameron et al. 1942) and acute bronchiolitis or peribronchiolitis in dogs (Clay and Rossing 1964). However, a lack of experimental details in the monkey and dog studies renders them inappropriate for AEGL derivation.

The chemical pneumonia observed in rats exposed to phosgene at 2 ppm for 90 min (Gross et al. 1965) will be used as the basis for deriving AEGL-2 values. This end point was chosen because at a C × t product of 180 ppm·min, approximately 60% of rats exhibited chemical pneumonia. Whereas, at C × t products ≤180 ppm·min, only 15% of exposed rats showed pneumonia or chemical pneumonitis. An uncertainty factor (UF) of 3 will be applied for interspecies extrapolation because little species variability is observed in lethal and nonlethal end points after exposure to phosgene. A UF of 3 will also be applied to account for sensitive human subpopulations due to the steep concentration-response curve and because the mechanism of phosgene toxicity (binding to macromolecules and irritation) is not expected to vary greatly between individuals. Thus, the total UF is 10. The concentration-time relationship for many irritant and systemically acting vapors and gases may be described by Cⁿ × t=k, where the n ranges from 0.8 to 3.5 (ten Berge et al. 1986). Haber’s law (C×t=k; n=1) has been shown to be valid for phosgene within certain limits and will be used for scaling of the AEGL values for phosgene for the 30-min and 1-, 4-, and 8-h time points. The 30-min value is also adopted as the 10-min value, because extrapolation would yield a 10-min AEGL-2 value close to concentrations producing alveolar edema in rats. The AEGL-2 values for phosgene are presented in Table 1–12, and the calculations for these AEGL-2 values are presented in Appendix A.

These AEGL-2 values are supported by the nonlethal toxicity studies of Franch and Hatch (1986) and Ehrlich et al. (1989). In both of these studies, rats exposed to phosgene at 1 ppm for 4 h developed severe pulmonary edema and body-weight loss. If this exposure regimen and a total UF of 10 are uti-