Developments in Carcinogenicity testing

Abstract

This review discusses developments during the last 60 years in field of carcinogenecity testing based on the use of laboratory animals. The first such study involved applications of Coal tar to the ear of rabbits. Improvements that have occurred in the quality of animals and in the way in which tests are conducted are considered, along with the importance of distinguishing between “Genotoxic” and “Nongenotoxic” carcinogens. Various Pharmaceuticals have been detected to give a positive result in the standard “Chronic Bioassay” which consist of and 18 to 24 months daily administration of test compound in the mice and rat. The high incidence of apparently false-positive result in the chronic bioassay may be due some deficiencies as oversensitivity and difference in mechanism of pharmacological action between rodents and human, but, these deficiencies provided ground to develop some alternative models for testing.  On the increased knowledge of cellular and molecular mechanism involved in carcinogenicity, extensive discussion have recently taken place between regulatory agencies and industry associations at the occasions of the International Conference Harmonization (ICH). For future prospects, a necessity for a better understanding of how disturbance of physiological and/or hormonal status can predispose to tumor development and for more comparative metabolism studies is stressed.

Key words: ICH, Genotoxic