Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in rats: CT-pathologic correlation

To investigate the acute and repeated pulmonary damage in Sprague-Dawley rats caused by the inhalation of 3-methoxybutyl chloroformate (3-MBCF) using computed tomography (CT), and to correlate these results with those obtained from a pathological study.

Sixty, 7-week-old rats were exposed to 3-MBCF vapor via inhalation (6 h/day) for 1 day (N=20), 3 days (N=20), and 28 days (5 days/week) (N=20) using whole body exposure chambers at a concentration of 0 (control), 3, 6 and 12 ppm. CT examinations including densitometry and histopathologic studies were carried out. For the follow-up study, the rats exposed for 3 days were scanned using CT and their pathology was examined at 7, 14, and 28 days.

There was a significant decrease in the parenchymal density in the groups exposed to the 3-MBCF vapors for 1 day at 3 ppm (p=0.022) or 6 ppm (p=0.010), compared with the control. The parenchymal density of the rats exposed to 12 ppm was significantly higher. The pathological findings in this period, the grades of vascular congestion, tracheobronchial exfoliation, and alveolar rupture were significant. In the groups exposed for 3 days, there was a large decrease in the parenchymal density with increasing dose (control: -675.48+/-32.82 HU, 3 ppm: -720.65+/-34.21 HU, 6 ppm: -756.41+/-41.68 HU, 12 ppm: -812.56+/-53.48 HU) (p=0.000). There were significant density differences between each dose in the groups exposed for 28 days (p=0.000). The CT findings include an irregular lung surface, areas of multifocal, wedge-shaped increased density, a heterogeneous lung density, bronchial dilatation, and axial peribronchovascular bundle thickening. The histopathology examination revealed the development of alveolar interstitial thickening and vasculitis, and an aggravation of the mainstem bronchial exudates and bronchial inflammation. The alveolar wall ruptures and bronchial dilatation became severe during this period. On the follow-up study, the groups exposed for 3 days showed diffusely increased parenchymal density on the 7 days study, but the lung densities were lower at 14 and 28 days than at 3 days. In the rats exposed to lowest concentration, the pulmonary parenchymal density and pathologic findings rapidly returned to normal within 1 week.

Decreased parenchymal density of the lung was a common CT finding in acute and repeated inhalation injury. The air accumulation is believed to be the results of tracheolaryngeal inflammatory edema, bronchial dilatation, and alveolar rupture from the early period.