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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lim
Yeon Soo
YS
Department of Radiology, Holy Family Hospital, College of Medicine, The Catholic University of Korea, Pucheon, Kyung gi-do 420-717, Republic of Korea.
Chung
Myung Hee
MH
Park
Seog Hee
SH
Kim
Hyeon-Yeong
HY
Choi
Byung Gil
BG
Lim
Hyun Wook
HW
Kim
Jin Ah
JA
Yoo
Won Jong
WJ
D000704:Analysis of Variance; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D001991:Bronchitis / Q000139:chemically induced / Q000000981:diagnostic imaging; D004108:Dilatation, Pathologic / Q000139:chemically induced / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005561:Formates / Q000009:adverse effects* / Q000633:toxicity; D007091:Image Processing, Computer-Assisted; D019570:Inhalation Exposure / Q000009:adverse effects*; D011650:Pulmonary Alveoli / Q000000981:diagnostic imaging / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012107:Research Design; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000473:pathology; D012720:Severity of Illness Index; D013997:Time Factors; D014057:Tomography, X-Ray Computed
C528637:3-methoxybutyl chloroformate; D005561:Formates; C083354:chlorocarbonic acid