Lung function changes in rats after chronic inhalation exposure to 4,4'-methylenediphenyldiisocyanate (MDI)

Female Wistar rats were exposed 17 h/day, 5 days/week for up to 24 months to 0.23, 0.70 and 2.05 mg/m³ MDI in aerosol form. A control group was kept in clean air. Lung function measurements after 6, 12 and 17 months of exposure carried out on the same animals of satellite groups showed a dose-dependent deterioration of lung function: significant reduction of lungvolumes, lung complianc, forced expiratory flow-volume parameters, CO diffusing capacity and marked inhomogeneity of alveolar ventilation. These findings revealed a dose-depending increasing impairment of the lung functions in the sense of a combined restrictive/periveral-obstructive malfunction with diffusions disorder, beginning earlier than 6 months of exposure, increasing at 12 months but not much further at 17 months. This correlates very well to the elevated hydroxyproline levels in the BAL fluid, to the increased lung weights and peribronchiolar fibrosis with narrowing and fibrotic wall thickening of small airways.