(60b) Comparing in Vitro Cytotoxicity Measurements to in Vivo Pulmonary Toxicity Profiles of Fine and Nanoparticles

Previous studies have reported little correlation between the relative toxicity of particles when comparing lung toxicity rankings following in vivo instillation compared to in vitro cell culture exposures. This study was designed to assess the capacity of in vitro screening studies to predict in vivo pulmonary toxicity of several fine or nanoscale particles in rats. In the in vivo component of the study, rats were exposed by intratracheal instillation to carbonyl iron, crystalline silica, precipitated amorphous silica, nano-sized zinc oxide, or fine-sized zinc oxide. For the in vitro component of the study, three different culture conditions were utilized. Cultures of rat lung epithelial cells, primary alveolar macrophages (collected via bronchoalveolar lavage (BAL) from unexposed rats), and lung epithelial cell/alveolar macrophage co-cultures were incubated with the particle-types listed above at numerous concentrations. Although results showed little correlation between in vitro and in vivo toxicity measurements, the best indicator for in vivo pulmonary toxicity of particles in rats was the lung epithelial cell/alveolar macrophage co-culture system incubated over a 1-48 hour time range. However, it seems clear that in vitro cellular systems will need to be further developed, standardized, and validated (relative to in vivo effects) in order to provide useful screening data on the relative toxicity of inhaled particles.