[International-cooperative studies on carcinogenicity evaluation of environmental chemicals]

Motivated by the epidemiological evidence suggesting that the majority of human cancers result from exposure to environmental carcinogens, an international cooperative project aiming at the primary prevention of cancers has been in progress to test a number of chemicals for potential carcinogenicity in animals. With accumulation of the test data, it has become apparent that for assessment of carcinogenic risk in humans, one sometimes needs, 2 kinds of additional information concerning the mechanism by which, and how intensely the test compounds can induce cancers in experimental animals. With regard to the mechanistic issues, extensive studies are now being conducted in various countries to establish a scientific basis for classifying chemical carcinogens into 3 categories, genotoxic (primary) carcinogens, epigenetic (secondary) carcinogens and promoters. As an approach to quantitative risk assessment of carcinogens, attempts have been made to estimate the "Virtually Safe Dose (VSD)" or carcinogenic doses at extremely low risk levels by downward extrapolation of animal dose-response data. Finally, it must be emphasized that most human cancers are probably etiologically attributable to a complex interaction of multiple factors. Therefore, the development of a methodology for evaluating the effect of combined or sequential exposure to 2 or more carcinogens is now regarded as an important project in cancer research.