Acrolein and two of its more stable derivatives, the oxime and the diethylacetal, and the related allyl alcohol were given in drinking water to groups of 20 male and 20 female F344 rats at doses close to the maximum that could be tolerated by the animals, for most of their lifetime. Acetaldoxime served as a control for the hydroxylamine derivative of acrolein. Most of the tumors were common in untreated rats of this strain. Only adenomas of the adrenal cortex in females were more numerous than in untreated controls. Acrolein itself was too toxic to hamsters to conduct a carcinogenesis study. Acrolein oxime, acrolein diethylacetal and allyl alcohol were all quite toxic to hamsters, but 2 mg per week by gavage was tolerated by groups of 20 male Syrian hamsters. There was a small number of tumors of the pancreatic ducts and of the forestomach in the treated hamsters, but the incidence was not statistically significant.
Saccharin is carcinogenic for the urinary bladder in rats and mice, and most likely is carcinogenic in human beings. The neoplasms of the urinary bladder are malignant and invade and metastasize. Male rats are more susceptible to urinary bladder carcinogenesis than female rats. Rats exposed as fetuses develop neoplasms more readily than rats exposed as weanlings. The lesions in the urinary bladder go through the stages of hyperplasia, hyperplastic nodules, and later carcinomas. The male of the human species ingesting saccharin, as for rats, is more susceptible to carcinogenesis of the urinary bladder than the female. Neoplasms of the urinary bladder in rats were not caused by stones, parasites, sodium, or impurities. There is a cocarcinogenic effect between saccharin and methylnitrosurea for the urinary bladder. Even through carcinomas of the urinary bladder are present in rats given the higher doses of saccharin, one was observed in a female rat given 0.5%. Chronic renal disease develops in rats ingesting saccharin. The disease is more advanced at the lower doses than at the higher doses, suggesting that saccharin at the lower doses does not reach the urinary bladder. Early neoplasms are seen in the renal pelvis of rats given the higher doses of saccharin. The risk ratios for urinary bladder carcinomas in human beings increase with both frequency andduration of saccharin usage. Benign and malignant neoplasms at all sites are significantly increased in mice and rats ingesting the higher doses of saccharin. These neoplasms are present in the reproductive and hematopoietic systems, and to a lesser extent in the lungs, vascular system and squamous epithelium. Neoplasms in some organs develop with the lower doses of saccharin. Lymphosarcomas of the lung are significantly increased in rats given 0.01% saccharin. Chronic renal disease in rats given saccharin interferes with the health and life span and consequently with development of neoplasms. Saccharin initiates neoplasms of the skin when its application is followed by croton oil. Epidemiological studies have not been done for neoplasms other than the urinary bladder in human beings.
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