EXPERIMENTAL ANIMAL STUDIES AND CARCINOGENICITY

Cancer Risk Assessment, edited by Ching-Hung Hsu and Todd Stedeford Copyright 2010 Jdin WQey Sons, Inc. 

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Epidemiological studies showed positive association of coffee drinking and cancers of pancreas and ovary (18,19,20), although reports describing negative association are also available (21,22). In an experimental animal study, no carcinogenic activity of coffee was reported (46,47). However, this data should be reconsidered in terms of the genotoxic activities of coffee revealed in bacteria and cultured mammalian cells. 

Toxicology. Amitrole has low acute toxicity in experimental animal studies subchronic exposures were associated with changes in the thyroid and chronic exposures were carcinogenic. 

Chronic studies in mice found adenomas and carcinomas of the duodenum after oral administration. The lARC has determined that there is limited evidence in experimental animals for the carcinogenicity of hydrogen peroxide and inadequate evidence in humans. ... 

In 2-year drinking water studies mice showed increased incidences of hepatocellular carcinomas and hepatoblastomas male Fischer 344 rats had increased incidences of renal tubule adenomas, and male Wistar rats showed evidence of interstitial cell adenoma of the testis. No increase in mmor incidence at any site was observed in rats after chronic subcutaneous injection. The lARC has determined that there is limited evidence in experimental animals for the carcinogenicity of pyridine and that it is not classifiable as to its carcinogenicity to humans. Pyridine was not genotoxic in a variety of assays. ... 

There is little in the literature relative to vitamin A and colon cancer in human populations. Experimental animal studies, however, strongly suggest that vitamin A deficiency may have a role in this type of cancer. We have shown that a deficiency of vitamin A increased DMH-induced tumors and shortened the lag time for induction, compared to normally supplemented controls (72). More recently (73) we have confirmed a protective role for vitamin A in colon carcinogenesis (Table XVII). Furthermore, we have shown (74) that vitamin A deficiency can result in colon tumors in rats given aflatoxin (AFB ) which is normally a liver carcinogen (Table XVIII). The colon tumors associated with the hepatocarcinogen AFB.. appear to be a result of differences in metabolism and binding of AFB or its metabolite ) to colon DNA under conditions of vitamin A deficiency (75). 

There is limited evidence of carcinogenicity of azathioprine in experimental animals. Studies with rats produced squamous cell carcinomas of the ear duct after administration at 150 mg kg in the diet for 52 weeks and lymphomas of the thymus gland under other conditions. In mice, intraperitoneal injections at 40 mg kg in 1-4-day-old offspring produced leukemia and long-term studies produced lymphoma and hemangiodothelioma of the uterus. 

The cost of this study was over 750,000. A two-year inhalation carcinogenicity study of TDI using rats and mice is costing over 400,000. Individual producers of TDI have done experimental animal toxicology and employee health evaluations. 

In addition to carcinogenic effects, animal studies have shown the effects of benzene exposure on the immune system. Reid et al. showed a significant decrease in splenic cell proliferation in mice exposed to benzene for 14 days. Experimental animal studies also reported reduced circulating white blood cells, as well as changes in spleen morphology and weight in various experimental animal studies. These experimental animal studies further support the observation from 1913 by Wintemits and Hirschfelder that rabbits exposed to... 

Experimental animal studies have established nitrosamines as a family of extremely potent carcinogens. Their cancer potencies are much higher than those of the trihalomethanes and it is for this reason that the International Agency for Research on Cancer (lARC) of the World Health Organization has focused great interest in this group of compounds. 

Bile acids— The diet—in particular fat—may have a role in the development of colon cancer. A current hypothesis is that high dietary fat intake (1) increases bile secretion, and (2) influences the composition and the metabolic activity of the intestinal microfloral so that the anaerobic clostridia increase. These microorganisms— clostridia—are capable of converting, by dehydrogenation, bile acids and neutral sterols (primary bile acids) to carcinogens or cocarcinogens—secondary bile acids. There is substantial evidence in experimental animal studies to implicate dietary fat and secondary bile acids eis colon cancer related. 

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