Types and amounts of carcinogens as potential human cancer hazards

Current knowledge on the mechanisms of chemical carcinogenesis forms the basis for application of select short-term in vitro and in vivo tests to detect potential human carcinogens, for ultimate application to hazard assessment. Chemical carcinogenesis involves a series of distinct steps, proceeding from the initiation of a neoplastic cell, through its promotion, development, and progression to cancer. Some chemicals act in each of these stages as initiators, cocarcinogens, promoters, or inhibitors of carcinogenesis. Chemicals can be classified as operating by genotoxic or epigenetic mechanisms, and appropriate tests can be used to detect such properties. These abbreviated tests provide enhanced qualitative decision-making potential since they are based on mechanisms of action. Advances in molecular biology may provide additional tests to detect cancer risk. The quantitative data available from in vitro dose-response studies indicate that carcinogenic effects are dose dependent and, therefore, a threshold or no-effect level probably exists, which is low for potent carcinogens (especially genotoxins) and high for weaker ones (particularly epigenetic agents).