Man made mineral fibre biopersistence and carcinogenicity

This study, integrated within the Colt Fibre Research Programme, examined the influence of fibre characteristics (length, diameter, durability, and inherent toxicity) on carcinogenicity in experiments involving several contrasting fibres: glass microfibre (100/475), silicon carbide whiskers, amosite asbestos, and size-selected (TIMA) fibres – MMVF10, MMVF21, MMVF22, RCF1, RCF2 and RCF4. For the TIMA fibres, statistical analyses incorporated information from inhalation studies performed by RCC, Geneva.An intratracheal biopersistence test and a simple in vitro assay of dissolution showed major differences between fibre types, and ranked fibre types similarly but not identically for durability of long fibres. Short term biological responses in vivo and in vitro were used to assess inherent toxicity; an epithelial proliferation assay (used on the 3 fibres tested by inhalation at IOM) showed most promise as indicative of pathogenicity.The fibres showed major differences in mesothelioma production (by intra-peritoneal injection) and fibrosis and pulmonary tumours (by inhalation). Ranking by injection was the same as by inhalation, except for two fibre types.For lung cancer incidence by inhalation, three variables were highly statistically significant: exposure to thin (< 1 /im) fibres longer than 8 /im, with a further contribution from exposure to thin fibres longer than 20 /im, and biopersistence of long fibres. More durable thin fibres produced higher incidence of tumours (by inhalation) and more rapid induction of mesothelioma (by intraperitoneal injection). The regression models gave reasonable predictions of cancer production from fibre characteristics. ""