LUNG CLEARANCE OF EXPERIMENTAL MAN-MADE MINERAL FIBRES, PRELIMINARY DATA ON THE EFFECT OF FIBRE LENGTH

The hazard from inhaled fibres is believed to be related to their dimensions, with long, thin fibres being potentially more carcinogenic than short, thick ones (Stanton et al., 1981; Pott, 1978) and to their biopersistence, as fibres which dissolve rapidly in the lung are unlikely to induce long-term pathological changes (Morgan and Holmes, 1986). Following deposition in the lung, short fibres (< 10-20 um in length) are ingested by alveolar macrophages, exposing them to the acidic environment of the phagolysome (pH 4.5). Longer fibres remain free in the lung tissue and are exposed to the neutral environment of the lung fluid. These longer fibres may be partially engulfed by macrophages, with macrophages gathering along the fibre like pearls on a string, exposing different parts of the fibre to different environments. These pH differences can explain the length dependent biopersistence observed for experimental glass fibres (Eastes et al., 1995). For these fibre types, short fibres (< 20 fim) showed only limited decline in diameter with time, indicating low dissolution. For longer fibres, diameter reduction was faster, indicating higher dissolution, similar to that seen in in vitro studies. This is consistent with the fact that glasses are more soluble at neutral pH than acidic pHs. For stone wool fibres, which are more soluble at low pHs, the situation should be reversed, with short stone wool fibres showing lower lung biopersistence than longer fibres. If pH is the determining factor, adjustment of the chemical composition of fibres may result in higher dissolution of longer fibres within the lung, reducing the potential hazard from these fibres. Studies on lung clearance of fibres (and hence biopersistence) present problems as thick fibres (respirable by humans) can not be inhaled by rats. With intratracheal instillation, longer and thicker fibres may be administered to the lungs of animals and measurements of biopersistence made. In this study, initial lung biopersistence results for two experimental MMVFs are compared and the effect of fibre length on clearance demonstrated. Corresponding data for biopersistence of both fibres in the peritoneal cavity and for HTN lung retention measured by SEM is currently being collated.