A comparison of methods of determining and predicting the pathogenicity of mineral fibers

Most authors consider that long-term inhalation studies represent the most reliable method of obtaining data on the pathogenicity of mineral fibers. However, because of the length of time required and the great cost of inhalation work, other methods of examining the biological effects of mineral fibers have been used. The program of work described here was designed to compare a wide range of techniques, including inhalation, for determining the biological effects of a selection of man-made mineral fibers. Silicon carbide whiskers were examined as a very durable material and also a less durable glass microfiber (code 100/475) as a relatively soluble man-made vitreous fiber. Amosite asbestos was used as a positive control. Long-term inhalation studies with full-life-span follow-up demonstrated that amosite and silicon carbide were both fibrogenic and carcinogenic in rats, while glass microfiber produced very little fibrosis and a few benign pulmonary tumors in numbers similar to those found in controls. Silicon carbide was unusual in that most of the tumors produced were pleural mesotheliomas. Early effects of the fibers were examined after a short period of inhalation, and the pathogenic dusts amosite and silicon carbide were found to produce rapid pulmonary inflammation as determined by the presence of significant numbers of neutrophils in pulmonary lavage fluid. Less pulmonary inflammation followed the inhalation of glass microfiber. Similarly, amosite and silicon carbide inhalation was found to cause a rapid increase in the rate of proliferation of bronchoalveolar lining cells, while the rate of cell division in animals treated with microfiber remained normal. When injected into the peritoneal cavities of rats, all three fiber types produced mesotheliomas, although the glass microfiber produced many fewer and these took much longer to develop. An examination of early inflammation in the peritoneal cavity of mice following rejection showed little difference between the fiber types, all of which caused raised numbers of neutrophils in peritoneal fluid. Fiber durability was examined both in viva and in vitro. Following inhalation it was found that fewer very long glass microfibers (>20 μm in length) remained in rats lungs after 12 mo of inhalation than amosite or silicon carbide. Subsequently, however, amosite and microfiber were removed from the lung at similar rates for most fiber dimensions, in contrast to silicon carbide fibers, where clearance was much less. When dust was administered by intratracheal injection, these differences in fiber removal from lung tissue were much less marked An examination of the in vitro solubility of fibers and their chemical composition after extraction from lung tissue demonstrated that glass microfiber showed significant leaching while amosite showed much less and silicon carbide showed almost no change in chemical composition. The possibility of using short-term in viva and in vitro tests to provide a screening system to eliminate the need for some of the longer and more expensive procedures is discussed.