Pulmonary biochemical effects of inhaled phosgene in rats

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Abstract
Three exposure regimens were used to study the time course of indicators of lung damage and recovery response to single or repeated exposures to phosgene (COCI 2 ). Rats were sacrificed (1) immediately or throughout a 38‐d recovery period after inhalation of 7 ppm COCI 2 for 4 h, (2) at intervals during a 7‐h exposure to 1 ppm phosgene, or (3) at several time points throughout a 17‐d exposure to 0.125 and 0.25 ppm COCI 2 (4 h/d, 5 d/wk) and during a 21‐d recovery period. Regimen 7 revealed significantly elevated lung wet weight, lung nonprotein sulfhydryl (NPSH) content, and glucose‐6‐phosphate dehydrogenase (G6PD) activity that stayed elevated for up to 14 d. A significant decrease in body weight and food intake was observed 7 d after exposure. Regimen 2 caused a slight depression in NPSH content but did not affect G6PD activity. Regimen 3 animals showed sustained elevations in lung wet weight, NPSH content, and G6PD activity after 7 d of exposure. No significant changes in these endpoints were observed for the 0.125 ppm COCI 2 group. No consistent elevation in hydroxyproline content was seen at either exposure concentration. Light microscopic examination of lung tissue exposed to 0.25 ppm COCI 2 for 17 d revealed moderate multifocal accumulation of mononuclear cells in the centriacinar region. In summary, exposure to COCI 2 caused changes similar in most ways to those observed for other lower‐respiratory‐tract irritants.