Influence of fibre length, dissolution and biopersistence on the production of mesothelioma in the rat peritoneal cavity

A range of respirable man-made mineral fibres were tested for evidence of c arcinogenicity by injection into the peritoneal cavity of male SPF Wistar r ats; and differences in carcinogenicity were related to the dimensions and biopersistence of the injected fibres, The fibres tested included an amosit e asbestos, a silicon carbide whisker, a special purpose glass microfibre, and a range of other man-made vitreous fibres (MMVFs) and refractory cerami c fibres (RCFs) from the TIMA fibre repository. The injected dose of each w as designed as the estimated mass required to contain 10(9) fibres >5 mu m in length, as determined by optical microscopy, The numbers of long fibres( > 15 mu m) contained in these doses ranged across fibres from 0.1x10(9) to 0.8x10(9) fibres; the number of long fibres thinner than 0.95 mu m ranged f rom 0.015x10(9) to 0.4x10(9). The treatment groups contained between 18 and 24 animals. Animals were killed when they showed signs of debilitation, At autopsy, the diagnosis of mesothelioma was usually obvious macroscopically . Otherwise, histological examination of peritoneal organs was used to sear ch for early tumour development. Judged by median survival time, four of th e fibre types, in the doses administered, presented higher mesothelioma act ivity than amosite asbestos. The other fibres tested were less carcinogenic than the amosite, Only a ceramic material derived by extreme heating to si mulate the effect of furnace or oven conditions, produced no mesotheliomas. Attempts were made, using regression models, to relate these differences t o fibre dimensions and to measures of durability from separate experiments. The results pointed principally to a link with the injected numbers of fib res > 20 mu m in length and with biopersistence in the rat lung of fibres l onger than 5 mu m. Improved quantification of the relative importance of fi bre dimensions and biopersisteuce indices requires experimentation with a r ange of doses. (C) 1999 British Occupational Hygiene Society. Published by Elsevier Science Ltd. All rights reserved.