PARADIGM SHIFTS IN EVALUATING HEALTH EFFECTS OF ASBESTOS: NON-CANCER OUTCOMES

Research findings are forcing us to consider a paradigm shift in the assessment of health outcomes of asbestos exposure. First, non-cancer outcomes must be considered as sensitive and impactful measures, potentially occurring at very low levels of exposure. The experience with Libby Amphibole (LA) has taught us that exposure predominantly causes a non-malignant pleural disease that has a progressive and atypical clinical presentation, and can increase the risk of systemic autoimmune diseases. Our studies also suggest that the two may be related mechanistically. Second, it is clear that we cannot assume that different types of fibers will have the same outcomes; therefore, fiber-specific risk assessments must take these non-cancer outcomes into account. Third, the public health impacts of these findings are highlighted in the growing awareness of "naturally occurring asbestos" in places where it was not previously predicted to occur, leading to environmental exposures in wide areas of the world. A mouse model has been used to compare the non-cancer effects in mice of exposure to LA with those of a newly discovered mixture of amphibole fibers from Arizona. The immune system plays a profound role in directing the outcomes of exposure, including cytokine shifts and development of autoantibodies, which can affect the ability to fight cancer, produce fibrosis or result in autoimmunity. We hypothesized that subtle differences in size and chemistry of fibers can affect the resulting immune dysfunction, and that the immune profile may predict ultimate health outcomes. The results demonstrated that LA is not unique in producing autoimmune outcomes in mice, and yet supported our hypothesis that the Arizona amphibole would cause a distinct immune profile despite chemical and morphological similarities with LA. We are demonstrating non-cancer outcomes at very low exposure levels in mice that we believe help us to model health risks of emerging environmental exposures.