Bladder cancer in rat

The artificial sweetener cyclamate was banned becanse of its link to bladder cancer in rats fed with large doses 20 snbseqnent studies have failed to confirm this result, but cyclamate remains banned. 

The artificial sweetener cyclamate was banned because of a study linking it to bladder cancer in rats when large doses were fed. At least 20 subsequent studies have failed to confirm this result but cyclamate remains banned. In 1977 saccharin was found to cause cancer in rats. It was banned by the FDA temporarily, but Congress placed a moratorium on this ban because of public pressure. In 1992 it was found that saccharin may cause cancer in rats but not in humans. Saccharin is still available today. A more recent sweetener, aspartame (Nutrasweef ), has also come under attack but has not been proven to be a problem since its introduction in 1981. 

It was also found that, under the conditions that led to bladder tumours, mineral deposits (microcalculi) were present in the bladder, which is known to cause bladder cancer in rats. 

It was thought by Dunning et al. (D7, D8) that the combined administration of 2-fluorenylacetamide and tryptophan could be a real factor in the initiation of bladder cancer in rats. It was argued (B18) that... 

D7. Dunning, W. F., Curtis, M. R., and Maun, M. F., The elFect of added dietary tryptophan on the occurrence of 2-acetylamino-fluorene-induced liver and bladder cancer in rats. Cancer Res. 10, 454-459 (1950). 

Bladder stone formation can lead to bladder cancer in rats and mice, thus making it difficult to be certain whether a chemical that leads to bladder stone formation and turnorigenesis is or is not a true animal and/or human carcinogen. 

Saccharin does not accumulate in body tissnes. Controversy over the use of saccharin has existed for over a century. In the 1960s and early 1970s saccharin and/or its impnrities were shown to canse bladder cancer in rats. 

A foriim entitled "Animal Tests and Human Cancer" vas reported in Chemical and Engineering News, June 27, 1977, with an eye-catching cover photo of a rat. The forum was prompted by the proposed ban on saccharin following the Canadian study which showed the induction of bladder cancer in rats. For the first time, it appeared the public was acutely aware of the impact of governmental regulatory legislation upon their personal lives. 

Wang, C.V., Hayashida, S., Pamakau, A.M. and Bryan, 6.T., 1976, Enhancing effect of allopurinol on the induction of bladder cancer in rats by N[4-(5-nitro-2-furyl)-2-thiazolyl] formamide. Cancer Res., 36 1551-1555. 

Pamukcu, A.M., and J.M. Price Induction of Intestinal and Urinary Bladder Cancer in Rats by Feeding Bracken Fern Pteris aquilina). J. Natl. Cancer Inst. 43, 275 (1969). 

It is recommended that daily saccharin intake be maintained below 1 g because of a risk of bladder cancer. A lifetime daily diet containing 5-7.5% saccharin has induced bladder tumors in rats [69]. However, it is probable that saccharin is only a very weak carcinogen in humans. The amount contained in pharmaceutical preparations is well below the recommended maximum human daily intake. 

Artificial sweeteners and saccharin (1977, US) High doses of the artificial sweetener had caused bladder cancer in lab rats... 

Saccharin is noncaloric and noncariogenic (2,3). The safety of saccharin for public health has been the center of several controversies. In 1970, saccharin at high dietary levels was observed to increase the incidence of urinary bladder cancer in experimental rats (1,59). However, extensive human epidemiological investigations showed that use of saccharin does not significantly increase the risk of bladder cancer (5,7,11,59). Saccharin is approved for use in several countries. Its use is not permitted in Canada, and a health warning on the label of saccharin-containing foods is required in the United States (7,8,10). 

Oral administration of dimethylaminoazobenzene has been shown to produce liver cancer in rats and bladder tumors in dogs. Carcinogenic effects have also been produced following dermal and subcutaneous applications in rats and mice. Dimethylaminoazobenzene is also a teratogen. 

The European Commission Scientific Committee for Food in 1997 established 1% sodium saccharin in the diet as a clear no-observed-effect level (NOEL) in relation to male rat bladder tumors and for other non-neoplastic effects of saccharin. In response to primarily updated experimental data and the extensive epidemiological data with no evidence of any relationship between saccharin intake and bladder cancer in humans, the Committee set a full acceptable daily intake (ADI) for sodium saccharin of 0-5 mg kg body weight. If the ADIs were expressed in terms of the free acid, since sodium saccharin is not the only salt used, and taking into account of the molecular weight difference between sodium saccharin (molecular weight 241) and the free acid (molecular weight 183), then ADI expressed as the free acid is 0-3.8 mg kg body weight. 

Figure 2. Dose—response curve for saccharin-induced bladder tumors in rats. Dose is expressed as per cent saccharin in the animals diets. Response (risk) is the fraction of animals in each dosed group developing bladder tumors over their lifetimes - also called the lifetime probability of bladder cancer. Data were reported by Taylor and co-workers, Toxicology and Applied Pharmacology, Vol. 29, page 1S4 (1974).

Clayson, D. B. (1974). Editorial Bladder carcinogenesis in rats and mice possibility of artifacts. J Natl Cancer Inst 52, 1685-1689. 

Kunze, E. (1979). Development of urinary bladder cancer in the rat. In Carcinogenesis, Grundmann, E., ed.. Springer-Verlag, Berlin, pp. 145-232. 

---