Guidelines for the evaluation of chemicals for carcinogenicity. Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment

Abstract

Chapter 1 gives some background information on general issues in chemical carcinogenesis. It briefly discusses mechanisms by which genotoxic and nongenotoxic substances may be involved in the development of cancer. The role of oncogenes and tumour-suppressor genes in molecular carcinogenesis is also described. The contribution from epidemiological studies to the overall assessment is dealt with in Chapter 2. The relative merits and limitations of different types of epidemiological investigations are discussed. Chapter 3 considers the major classes of chemical carcinogens with regard to the different mechanisms by which they exert their carcinogenic effects. The rôle of metabolism is considered. Chapter 4 covers the use of short-term predictive tests for screening for carcinogenic potential of chemicals (mutagenicity tests and cell transformation assays). Reference is made to the strategy for mutagenicity testing given in the Committee on Mutagenicity's 'Guidelines for the Testing of Chemicals for Mutagenicity', which is also relevant to predictive short-term testing for carcinogenicity. The main points to be considered in designing a carcinogenicity bioassay are covered in Chapter 5, and some of the problems which might be encountered during the performance of such a study are discussed. Special problems associated with the carcinogenicity testing of certain classes of substances are reviewed. The interpretation of the results of carcinogenicity studies is covered in Chapter 6. Statistical methodology is not dealt with in detail, but reference is made to more specialized guidelines. Advice is given on the problems of interpreting the biological significance of results. A number of factors which can influence the interpretation of the results of a study (confounding factors) are examined. Mechanisms of carcinogenicity are discussed in the context of interpreting the relevance to humans of a carcinogenic response in animals. Assessment of the hazards and risks from exposure to chemical carcinogens is discussed in Chapter 7. It explains the COC's differential handling of carcinogens, depending on whether or not a threshold level of exposure can be set for the chemical's carcinogenicity. It is proposed here and in earlier Chapters that threshold levels of exposure (below which there is no carcinogenic hazard) can reasonably be set for many non-genotoxic carcinogens if their modes of action are understood but not for genotoxic carcinogens (which are assumed to present a finite carcinogenic risk at any level of exposure). Methods of quantitative risk assessment of exposures to non-threshold (presumed genotoxic) carcinogens are briefly presented, and the COC's reasons for not using such methods are set out.(ABSTRACT TRUNCATED AT 400 WORDS)