The effects of long-term ingestion of asbestos on the colon of F344 rats

Abstract

Weanling F344 rats, which were fed a diet containing 10% chrysotile (B), were studied over their life-time to determine the effects of ingested asbestos on the colon. Control groups consisted of rats fed a diet containing a 10% nonnutritive cellulose or a standard laboratory rat diet. The pathological findings in the colons of 501 rats (189 on asbestos diet, 197 on fiber control diet, and 115 on standard control diet), are reported here. Epithelial tumors of the colon (eight adenocarcinomas and one adenoma) were found in nine of the rats on study. Four of the tumors were in asbestos-fed rats, two tumors were found in the non-nutritive cellulose controls, and three tumors were found in the standard laboratory rat diet controls. The probability (based on actuarial analysis) of developing adenoma or adenocarcinomas during the 32 months of the study were 7.4% for the asbestos-fed group, 3.5% for the fiber control diet and 4.0% on the standard control diet. In addition, one malignant mesothelioma of the type induced by intraperitoneally administered asbestos was found in the asbestos-fed group. Non-neoplastic lesions of the colon were also evaluated. The cumulative risk for development of any colon-associated lesion (non-neoplastic plus neoplastic lesions) was greatest for asbestos-fed rats (17.9%), compared to 13.6% for those fed the fiber control diet and 8.2% for those fed the standard control diet. The colon tissue levels of adenosine, 3'-5'-cyclic monophosphate (cAMP) were significantly lower in the animals fed asbestos compared to the control diets. Chrysotile fibers were seen by electronmicroscopy (e.m.) in six of ten ashed colon specimens of rats fed the asbestos diet. Although the differences in numbers of tumors between the animals fed asbestos and the controls were not statistically significant at the 5% level, we felt that the combination of observations including 1) evidence of increased probability of asbestos-fed animals to develop colon lesions in general; 2) evidence of a special type of mesothelioma in rats fed asbestos; 3) evidence for a cell regulator defect (lowered cAMP levels) in colon tissues of animals fed asbestos; and 4) evidence for asbestos fiber penetration of the colonic mucosa (e.m. studies) suggest that ingested asbestos is not inert in the colon.

Review of published studies of orally administered asbestos.

“…The authors did not provide any information regarding the size and shape of the asbestos fibers that were incorporated into the filter material. Although 12 malignant tumors were noted in the asbestosexposed group of rats and the mean survival time was decreased in the asbestos-treated group, the authors stated that no conclusions could be made from their test results regarding the pathogenesis of the tumors caused by the oral intake of asbestos material. The relationship of this study to asbestos carcinogenicity was also confounded by the presence of several substances in the filter material, which were not clearly identified.…”

Chronic effects of dietary exposure to amosite and chrysotile asbestos in Syrian golden hamsters.

“…Donham et al (11) reported equivocal results in F344 rats which were fed a diet containing 10% chrysotile for their lifetime. While they did not observe a statistically significant (p < 0.05) increase in the number of tumors in exposed animals, the authors believed that there was a trend toward increased colon lesions in general, evidence of penetration of asbestos into the colonic mucosa and possible cytotoxicity to colonic tissues and they suggested a possible relationship to peritoneal mesothelioma.…”

“…While they did not observe a statistically significant (p < 0.05) increase in the number of tumors in exposed animals, the authors believed that there was a trend toward increased colon lesions in general, evidence of penetration of asbestos into the colonic mucosa and possible cytotoxicity to colonic tissues and they suggested a possible relationship to peritoneal mesothelioma. Another equivocal study is that reported by Gibel et al (12), who described an increase in malignant tumors in the lung, kidney, liver and reticuloendothelial system, but no increase in intestinal neoplasia in Wistar rats fed asbestos filter material (20 mg/day) for a period of [8][9][10][11][12][13][14] (14), who fed rats a diet containing 5% chrysotile asbestos for a period of 21 months with no evidence of intestinal neoplasia.…”

Asbestos penetration of the gastrointestinal tract.

“…There have been at least 12 animal studies involving rats and baboons (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Five rat studies (4)(5)(6)(7)(8) and two baboon studies (8-10) presented evidence of asbestos penetration of the GI tract and/or migration to various tissues.…”

“…Five rat studies (4)(5)(6)(7)(8) and two baboon studies (8-10) presented evidence of asbestos penetration of the GI tract and/or migration to various tissues. Three rat studies (11)(12)(13) and two baboon studies (14,15) found little or no evidence of penetration and migration.…”