Abstract

The mesothelial lining is a target for the fibrotic and carcinogenic effects of mineral fibers. Fiber geometry, dimensions, chemical composition, surface reactivity, and biopersistence at the target tissue have been proposed to contribute to these toxic endpoints. We established a dose-response relationship between the number of fibers delivered to the parietal peritoneal lining, inflammation, and mesothelial cell proliferation induced by intraperitoneal injection of crocidolite asbestos fibers in mice. Persistence of these inflammatory and proliferative responses depended on persistence of fibers at the target tissue. Intraperitoneal injection of wollastonite fibers induced an early inflammatory and proliferative response that subsided after 21 days. Approximately 50% of wollastonite fibers were recovered by bleach digestion after 21 days and only 2% were recovered after 6 months. In contrast, the number of fibers recovered from tissue digests had not declined 6 months after injection of crocidolite asbestos. These results support the hypothesis that biopersistent fibers cause persistent inflammation and chronic mesothelial cell proliferation.

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