Non-genotoxic carcinogens. Approaches to their risk assessment

Epidemiological studies support the idea that most human cancers are related to chemicals present in the human environment. In turn, chemicals are believed to cause cancer via either genotoxic or non-genotoxic mechanisms. There were described in literature several simple, rapid and inexpensive short term tests to reasonably predict the genotoxic nature of chemicals but in contrast, there is no reliable test or battery of tests available to predict the carcinogenicity of non-genotoxic compounds and this poses a major problem to their risk assessment. In addition, there are conflictive opinions about risk assessment needs for both classes of carcinogens. Some workers believe that for non-genotoxic carcinogens, thresholds for exposure can be drawn while others do not. In this review, the reasons behind both of these opinions and the present hypotheses about the mechanism of action of non-genotoxic carcinogens are described and analyzed in relation to future needs.