In vivo assessments of pulmonary toxicity following exposure to inhaled fibers: Utilization of bronchoalvelolar lavage (BAL) and fixed lung tissue to assess fiber deposition patterns and early cellular responses

There is a great need for the development of a rapid and reliable short-term bioassay to evaluate the toxicity of inhaled particles and fibers. We have hypothesized that the pulmonary toxicity of particulates can be assessed by exposing animals to aerosols for short duration (1-5 days) and measuring a variety of biochemical, cellular and histopathologic endpoints at several time point postexposure. In this presentation, we have attempted to test the efficacy of our shortterm inhalation bioassay, by exposing rats to various doses of either α-quartz silica or crocidolite asbestos, known fibrogenic materials, as well as wollastonite fibers or carbonyl iron particles. Following exposures, fluids and cells from sham and dust exposed rats were recovered by lavage (BAL) and measured for enzymes, protein, cellular differentials an cytochemical analysis. Pulmonary macrophages were cultured and studied for morphology, chemotaxis and phagocytosis. The lungs of additional animals were fixed for light microscopic histopathology and autoradiography, as well as scanning and transmission electron microscopy, where particle/fiber deposition and translocation were assessed. The results from biochemical and cellular studies support the conclusion that silica and crocidolite are substantially more toxic to the lungs than wollastonite or carbonyl iron, and serves to lend support to the establishment of this method as a reliable shortterm bioassay for evaluating the lung toxicity following inhalation of a variety of inhaled materials