The modification of cancer risk by chemicals.

ABSTRACT

Advances in understanding of the process of carcinogenesis have undermined the concept of chemicals being classifiable as either carcinogens or non-carcinogens. Elements of carcinogenesis are happening all the time and a proportion of cancers cannot be prevented, the 'bad luck hypothesis'. Although the proportion that can be prevented is disputed, it is important to continue efforts to reduce it. Factors that increase cancer risk have been grouped into intrinsic factors that cannot be modified, and endogenous and exogenous factors that can be modified. Chemicals are exogenous factors that can be modified by risk management measures. Chemicals can alter three key rates that influence cancer risk cell division, mutation rate per cell division, transformation rate of mutated cells to cancer. These rates can form the basis of a dynamic cancer risk model, a generic, adverse outcome pathway for carcinogenesis where chemicals are considered for their ability to modify cancer risk rather than simply whether they are classed as carcinogens or non-carcinogens. This allows the development of different strategies for assessing cancer risk that use a range of data sources and are not dependent on using long-term bioassays and epidemiology to identify carcinogens. The framework will also allow difficult questions such as the effect of less than lifetime exposures and the effect of exposures to more than one chemical to be addressed.