Problems in the Evaluation of Carcinogenicity (Recent Evidences on Dynamics in Environment and Toxicity of Organochlorine Compounds) (Proceedings of the 11 th Symposium on Environmental Pollutants and Toxicology)

Abstract

As motivated by the epidemiological evidence suggesting that the majority of human cancers result from exposures to environmental carcinogens, an international cooperative project aiming at the primary prevention of cancers has been proceeded to test a number of chemicals for potential carcinogenicity in animals. With accumulation of test data, it becomes aware that for carcinogenic risk assessment in human, one needs, at times, 2 kinds of additional informations concerning 1) by which mechanism and 2) how intensely the test compounds can induce cancers in experimental animals. Regarding the mechanistic issues, the WHO expert committee members have discussed 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, it is attempted to estimate Virtually Safe Dose (VSD)or carcinogenic doses at extremely low risk levels by downward extrapolation of animal dose-response data. Various mathematical models such as one-hit model, probit model, logit model, multi-hit model or Weibull model are proposed for the purpose. Finally, it must be emphasized that most human cancers might be etiologically attributable to a complex interaction of multiple factors. Therefore, the development of methodology for evaluating the effect of combined or sequential exposures of 2 or more carcinogens is now regarded as an important project in cancer research.