Tumorigenicity of cellulose fibers injected into the rat peritoneal cavity.
Cellulose fibers, along with many other organic fibers, are durable. Therefore, if inhaled, they have the potential to persist within the lung, and may then cause disease. Here we report the effects of injecting high-purity cellulose fibers into the abdominal cavity of rats. A respirable fraction of cellulose fiber was collected from an aerosol of a thermo-mechanically-processed wood pulp. A sample of respirable crocidolite asbestos, known to produce mesotheliomas in rats, was used as a positive control. Total doses of 10(6), 10(7), 10(8), or 10(9) WHO fibers were injected intraperitoneally as 3 weekly aliquots. A negative control was provided by phosphate-buffered saline used to suspend the fibers for injection. There were 50 rats per treatment group except for the 10(8) and 10(9) fibers crocidolite groups which were reduced to 26 rats because of the expectation of high tumor incidence in these groups. The two higher doses of crocidolite asbestos caused greatly reduced survival compared to the saline controls. With cellulose there was a much less marked effect on survival. In the highest dose cellulose group, multiple large nodules (granulomas) and widespread adhesions (bands of new tissue connecting organs to each other and to the abdominal wall) were present in all animals. Granulomas were not observed in the 10(9) fibers crocidolite group. More than 80% of animals in the 10(8) and 10(9) crocidolite asbestos groups had mesotheliomas, a type of tumor sometimes observed in people exposed to asbestos. In contrast, there were only 2 animals in the cellulose groups with mesothelioma tumors, 1 in the 10(7) and 1 in the 10(8) groups. However, 9 (18%) of the 10(9) cellulose group had malignant tumors that, in contrast to the usual pattern of mesothelioma development following treatment with mineral fibers in rats, showed no obvious involvement of mesothelial tissues, were not associated with blood-stained ascites fluid, and were thus classified as sarcomas. This study has demonstrated that a high dose of cellulose fibers is capable of producing tumors when injected into the abdominal cavity of rats.
Institute of Occupational Medicine, 8 Roxburgh Place, Edinburgh EH8 9SU, UK. richard.cullen@iomhq.org.uk
R T
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Cullen
B G
BG
Miller
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Clark
J M G
JM
Davis
D000395:Air Pollutants, Occupational / Q000633:toxicity; D000818:Animals; D017638:Asbestos, Crocidolite / Q000633:toxicity; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D002482:Cellulose / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D020714:Maximum Tolerated Dose; D008654:Mesothelioma / Q000209:etiology; D019016:Mineral Fibers / Q000633:toxicity; D010316:Particle Size; D010534:Peritoneal Neoplasms / Q000209:etiology*; D010997:Pleural Neoplasms / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D012513:Sarcoma, Experimental / Q000209:etiology*
D000395:Air Pollutants, Occupational; D002273:Carcinogens; D019016:Mineral Fibers; D017638:Asbestos, Crocidolite; D002482:Cellulose