Rapid in vivo assessment of toxicity of respirable particles: a concise report

To study the in vivo toxicity of respirable particles, bronchoscopic catheterization of the sheep tracheal lobe was used to expose a limited area of the lung. After control studies, 3 groups of 6 sheep received one exposure to either 100 ml saline, 100 mg of latex beads (1.0 mu diam.) in saline or 100 mg of UICC Canadian chrysotile asbestos in saline. The animals were studied at day 1, 8, 15, 22 and 29 by pulmonary function tests (PFT) and bronchoalveolar lavage (BAL). At day 29, the sheep had chest roentgenograms (CR) and were autopsied. In all sheep, PFT did not changed and CR showed minimal infiltrates only in the asbestos-exposed sheep. In the saline sheep, BAL and lung histology did not change. In the latex sheep, at day 1 total BAL cells increased to 370%, macrophages to 215% and neutrophils to 650% (P less than 0.01) without change in BAL proteins or enzymes. These returned to control levels at day 8 and after except for a slight increase in BAL neutrophils. The lung histology showed inflammatory changes without architectural distortion. In the asbestos sheep, the day 1 response was comparable to latex group in terms of BAL cellularity but BAL neutrophils remained significantly elevated at 40% total BAL cells at day 8, 15, 22 and 29. Also lactate dehydrogenase (LDH) and beta-glucuronidase in BAL were significantly elevated from day 1 to day 29. At autopsy, the tracheal lobe of asbestos sheep had pneumonia-like neutrophilic infiltrates in the surroundings of the peripheral airways with early peribronchiolar fibrosis. This new in vivo model can clearly and rapidly differentiate the relative toxicity of respirable particles in the lung tissue and thus should be a useful tool in environmental lung research.