AN INVIVO HAMSTER BIOASSAY TO ASSESS THE TOXICITY OF PARTICULATES FOR THE LUNGS

A short-term bioassay was developed to predict the toxicity of particulates for the lungs using hamsters exposed by intratracheal instillation. After exposure the animals were killed, their lungs were lavaged and the pulmonary damage was characterized by cellular and biochemical assays of lavage fluid: changes in in situ phagocytic ability of macrophages; damage to the air-blood barrier shown by increases in albumin and red blood cells; inflammation shown by increases in polymorphonuclear neutrophils (PMN) and macrophages; and cellular damage, measured by the levels of lactate dehydrogenase (LDH), .beta.-N-acetylglucosaminidase, peroxidase and elastase in the extracellular supernatant fraction of the lavage fluid. The system was calibrated using toxic .alpha.-quartz and 2 nontoxic dusts, Al2O3 and iron oxide. Increases in albumin and red blood cells 1 day after exposure were greater following quartz than Al2O3 and iron oxide; a large part of the LDH increase was a nonspecific response to increased dust within the lungs. Most indicators, including red blood cell numbers, glucosaminidase and peroxidase, approached or were at control levels 4 days after exposure to iron oxide or .alpha.-quartz. In .alpha.-quartz-exposed animals, macrophage and PMN numbers were more elevated at 4 days than at 1 day and remained elevated for at least 14 days. In iron oxide-exposed hamsters, macrophage numbers did not differ from control levels and PMN numbers approached control levels with time. The ability to cause a prolonged infiltration of macrophages and PMN may be an important determinant of the toxicity of mineral dusts.