Carcinogenicity testing, long-term

Shelby MD, Stasiewicz S. 1984. Chemicals showing no evidence of carcinogenicity in long-term, two-species rodent studies The need for short-term test data. Environ Mutagen 6 871-878. 

M. D. Shelby and S. Stasiewicz, Environ. Mutagen., 6, 871 (1984). Chemicals Showing No Evidence of Carcinogenicity in Long-Term, Two-species Rodent Studies The Need for Short- Ierm Test Data. 

Pyridine Chronic Toxicology. AH mutagenicity tests have been negative and (1) is not considered a carcinogen or potential carcinogen. There have been no reports of adverse health effects on long-term exposure to (1) at low concentrations. 

The huge advances made in molecular biology since the late 1980s have provided the possibility of approaches to evaluating chemicals and potential drugs for carcinogenic potential in approaches which are different, less expensive and which take a shorter period of time than traditional long-term bioassays. This work has also been stimulated by dissatisfaction with the performance of traditional test systems. 

As performance data has become available on these strains, ICH (1997) has incorporated their use into pharmaceutical testing guidelines in lieu of the second rodent species tests (that is, to replace the long-term mouse bioassay when the traditional rat study has been performed). FDA has stated that they would accept such studies when performed in a validated model. In fact, CBER has accepted such studies as a sole carcinogenicity bioassay in some cases where there was negative traditional genotoxicity data and strong evidence of a lack of a mechanistic basis for concern. 

Kurokawa Y, Takayama S, Konishi Y (1986) Long-term in vivo carcinogenicity tests of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan. Environ... 

Peto R, Pike M, Day N, et al. Guidelines for simple sensitive significance tests for carcinogenic effects in long-term animal experiments. lARC Monogr 1980 (Suppl 2) 311 26. 

Weisburger EK, Russfield AB, Homburger F, et al Testing of 21 environmental aromatic amines or derivatives for long-term toxicity or carcinogenicity. J Environ Pathol Toxicol 2 325, 1978... 

Data on the Irritants are insufficient to evaluate their mutagenicity, carcinogenicity, or other long-term effects. Tests of all theses chemicals involved few exposures and low doses. 

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