Durability of man-made fibres and their clearance from the lung: studies to complement the Colt Fibre Programme

Early results from the Colt Fibre Research Programme (CFRP) suggested that both the number of long thin fibres in the received dose and the ability of these fibres to persist within the lung (biopersistence) are important predictors of carcinogenicity in animal experiments. This, report describes the results of some complementary studies, including cprhpietion of some biopersistence studies initiated during the CFRP and examination of a further fibre type; E glass.The biopersistences of ten fibre types were investigated in an intratracheal injection experiment. The lung burden data are consistent with the hypothesis that short fibres are largely cleared by cellular processes whereas long fibres are cleared-by the combined processes of dissolution and disintegration. The relative persistence of long fibres was similar to that in an in vitro dissolution assay. The biopersistence of four fibre types was also investigated following 12 months inhalation. The greater persistence of these fibres following inhalation is consistent with mild overloading of cellular clearance mechanisms. The composition of 100/475 fibres retained in lung over 12 months was substantially modified by differential leaching whereas the compositions of retained fibres of 104E and amosite were not.The two microfibres tested, 104E and 100/475, had similar biopersistences and showed a similar level of activity in cell tests. Cell proliferation following short term exposure to the 104E was, however, substantially elevated relative to that seen with the 100/475. The microfibres showed very different carcinogenic potentials with 104E being as or more active than amosite asbestos in chronic inhalation and intraperitoneal experiments.Statistical analyses of data from both the inhalation and injection studies suggested that important explanatory variables of the carcinogenic potential of fibres included the numbers or concentrations of long thin fibres, and measures of their ability to persist in the lung. However, the analyses showed that the available data could not predict all of the range of variability in carcinogenicity, failing in particular to explain the difference in the inhalation experiment between 104E and 100/475. This suggests a role for some other factor(s), possibly related to surface properties. It is suggested that modification of fibre surfaces by preferential leaching in the lung might have such an effect.