The importance of fiber biopersistence and lung dose in determining the chronic inhalation effects of X607, RCF1, and chrysotile asbestos in rats

The chronic inhalation effects in rats of X607 (a rapidly dissolving synthe tic vitreous fiber) were compared with those previously reported for RCF1 ( a refractory ceramic synthetic vitreous fiber) and chrysotile asbestos. Of primary concern was the importance of biopersistence as a mechanism of fibe r toxicity. Fischer rats were exposed to fiber aerosol by nose-only inhalat ion for 6 h/day, 5 days/week for 2 years. X607 and RCF1 aerosols were simil ar in concentration (similar to 200 fibers/cc) and average dimensions (appr oximately 20 x 1 mu m). Chrysotile aerosol was higher in concentration (10, 600 fibers/cc) and an order of magnitude smaller in average dimensions. Lun g fiber deposition after 6 h inhalation was greater for X607 than for RCF1. However, at later time points, fibers/lung (especially long fibers) were m uch lower for X607 than for RCF1, suggesting less biopersistence for X607. X607 was neither fibrogenic nor tumorigenic and induced only minimal lung c ellularity that reversed after exposure was terminated. In contrast, RCF1 a nd chrysotile asbestos induced pulmonary fibrosis and thoracic neoplasms (c hrysotile induced 32% more pulmonary neoplasms than RCF1). Lung deposition and fiber lengths did not explain the toxicologic differences between the t hree fibers. Fiber biodurability, including chemical and physical parameter s, appears to be a major toxicologic determinant here. Chemical analysis of lung fibers revealed rapid leaching of X607 compared to RCF1. In in vitro dissolution tests, X607 underwent rapid dissolution (k(dis) = 990 ng/cm(2)/ h) and transverse fragmentation, RCF1 dissolved slowly (k(dis) = 6 ng/cm(2) /h) and did not fragment, and chrysotile dissolution was negligible (<0.1 n g/cm(2)/h). (C) 1998 Academic Press.