DOSE-RESPONSE RELATIONSHIPS BETWEEN INHALED BERYLLIUM METAL AND LUNG TOXICITY IN C3H MICE

Inhaled beryllium (Be) can induce a range of adverse pulmonary respons es in animals and humans including acute pneumonitis, chronic granulom atous lung disease, and cancer. To facilitate comparisons with our pre vious data describing Be toxicity in rats, we evaluated the toxic effe cts of inhaled Be metal in mice. Groups of 34 strain C3H/HeJ mice were acutely exposed by the nose-only route to aerosolized Be metal to ach ieve measured initial lung burdens of 0, 1.7, 2.6, 12, or 34 mu g. All mice received aerosolized Sr-85-labeled fused aluminosilicate particl es (Sr-85-FAPs) immediately before their Be exposure so that the influ ence of Be on lung retention of these poorly soluble tracer particles could be externally quantitated. Groups of mice were euthanized at 8, 15, 40, 90, 210, and 350 days after exposure for evaluation of histopa thological changes and for cytologic and biochemical indicators of lun g damage measured in bronchoalveolar lavage fluid. Clearance of Sr-85- FAP tracer particles through 196 days after exposure was delayed in mi ce receiving the 12 and 34 mu g Be lung burdens, but not the 1.7 or 2. 6 mu g lung burdens. Increased total cell numbers, increased percentag e of neutrophils, and elevated levels of total protein and the activit ies of beta-glucuronidase and lactate dehydrogenase in bronchoalveolar lavage fluid were observed in the two highest Be lung burden groups c ompared with controls. Lung lesions included particle-containing macro phages, granulomatous pneumonia, lymphocytic interstitial aggregates, and mononuclear interstitial infiltrates. These lesions were occasiona lly seen in mice receiving the 2.6 mu g lung burden, were present in m ost of the mice receiving 12 or 34 mu g lung burdens, and were general ly increased in severity with time and lung burden. Thus, we have demo nstrated that a single, acute inhalation exposure to Be metal can chro nically retard particle clearance and induce lung damage in mice. The initial lung burdens used caused responses ranging from no apparent ef fects to significant Be-induced responses. A comparison of these data with our previous data from rats indicates that the mass of Be metal r equired to induce lung damage in mice is similar to that needed for ra ts. When expressed on a lung weight-normalized basis, mice appeared to be more resistant to the toxic effects of inhaled Be than rats.