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 carcinogenicity by injection into the peritoneal cavity of male SPF Wistar rats; and differences in carcinogenicity were related to the dimensions and biopersistence of the injected fibres. The fibres tested included an amosite asbestos, a silicon carbide whisker, a special purpose glass microfibre, and a range of other man-made vitreous fibres (MMVFs) and refractory ceramic fibres (RCFs) from the TIMA fibre repository. The injected dose of each was designed as the estimated mass required to contain 10(9) fibres > 5 microns in length, as determined by optical microscopy. The numbers of long fibres (> 15 microns) contained in these doses ranged across fibres from 0.1 x 10(9) to 0.8 x 10(9) fibres; the number of long fibres thinner than 0.95 micron ranged from 0.015 x 10(9) to 0.4 x 10(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 search for early tumour development. Judged by median survival time, four of the fibre types, in the doses administered, presented higher mesothelioma activity than amosite asbestos. The other fibres tested were less carcinogenic than the amosite. Only a ceramic material derived by extreme heating to simulate the effect of furnace or oven conditions, produced no mesotheliomas. Attempts were made, using regression models, to relate these differences to fibre dimensions and to measures of durability from separate experiments. The results pointed principally to a link with the injected numbers of fibres > 20 microns in length and with biopersistence in the rat lung of fibres longer than 5 microns. Improved quantification of the relative importance of fibre dimensions and biopersistence indices requires experimentation with a range of doses.
Miller
B G
BG
Institute of Occupational Medicine, Edinburgh, UK.
Searl
A
A
Davis
J M
JM
Donaldson
K
K
Cullen
R T
RT
Bolton
R E
RE
Buchanan
D
D
Soutar
C A
CA
D000818:Animals; D017639:Asbestos, Amosite / Q000009:adverse effects* / Q000032:analysis; D001673:Biodegradation, Environmental; D017554:Carbon Compounds, Inorganic / Q000009:adverse effects* / Q000032:analysis; D015197:Carcinogenicity Tests; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005898:Glass / Q000032:analysis; D008297:Male; D008654:Mesothelioma / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D019016:Mineral Fibers / Q000009:adverse effects* / Q000032:analysis; D009374:Neoplasms, Experimental / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017655:Silicon Compounds / Q000009:adverse effects* / Q000032:analysis; D016019:Survival Analysis; D013997:Time Factors
D017554:Carbon Compounds, Inorganic; D019016:Mineral Fibers; D017655:Silicon Compounds; D017639:Asbestos, Amosite; C022088:silicon carbide