EARLY DAMAGE INDICATORS IN THE LUNG .3. BIOCHEMICAL AND CYTOLOGICAL RESPONSE OF THE LUNG TO INHALED METAL-SALTS

The validity of using the enzymatic and cytologic profile of airway fluids to indicate lung damage was tested in animals exposed by inhalation to either a known toxic metallic salt (CdCl2) or a relatively innocuous salt (CrCl3). The enzymatic and cytologic response of the airways was compared to histopathological evaluation of lung damage. Syrian hamsters were exposed to an aerosol of CdCl2 (aerodynamic diameter = 1.7 μm, σg {reversed tilde equals} 1.7) to achieve an initial lung burden (ILB) of 0.6 ± 0.3 and 4.4 ± 1.2 μg of CdCl2 or to an aerosol of CrCl3 (count median diameter = 1.2 μm, σg {reversed tilde equals} 1.5) to achieve an ILB of 0.7 ± 0.2 or 20 ± 10 μg of CrCl3. Animals were sacrificed at 2 hr, 1, 7, and 21 days after exposure. A sample of airay fluid was obtained by bronchopulmonary lavage and examined for the enzymatic profile of the cell-free fraction and the cytological profile of the cell fraction. Lung tissue enzyme activities were also measured and histopathologic evaluations were made on lung tissue from exposed, but nonlavaged, animals. In the lavage fluid from animals exposed to CdCl2, the enzymatic and cytologic data demonstrated a dose-response pattern and the airway response preceded enzymatic changes in the lung tissue. Tissue morphological changes correlated well with the biochemical changes. The response of the lung to CrCl3 was minimal by both morphological and biochemical evaluations. Airway enzymatic and cytologic responses were shown to be potentially useful as indicators of lung damage in toxicological screening programs. © 1979.