Mechanisms of fiber-induced diseases: implications for the safety evaluation of synthetic vitreous fibers.

Inhalation of certain natural mineral fibers, such as amphibole asbestos, is associated with the development of inflammatory, fibroproliferative, and neoplastic diseases in the lung and pleura of man and experimental animals. The mechanisms by which fibers induce fibrosis and cancer are largely unknown, but are thought to be modulated by reactive oxygen species and altered growth factor pathways. Studies in rats using intracavitary implantation and instillation of fiber preparations led to the belief that all fibers with certain dimensional characteristics had similar toxic potential. It is now known that different fiber types of similar dimension can vary substantially in biological activity. A variety of physicochemical properties govern fiber toxicity and carcinogenicity, including: size and shape; surface chemistry; solubility and biopersistence; and chemical composition. Although the molecular event(s) that translate fiber-induced cellular injury into a pathologic state are unknown, there is strong evidence in man and laboratory animals to suggest both dose dependency and thresholds for effects.