Strategy for mutagenicity testing
The approach presented in this paper (see Figure 1) focuses on the identification of mutagens and genotoxic carcinogens. The term ‘mutation’ as understood in this paper (a glossary of terms used in this paper is available on the IPCS website at http://www.who.int/ipcs/publications/methods/harmonization/en /index.html) refers to permanent changes in the structure and/ or amount of the genetic material of an organism that can lead to heritable changes in its function, and it includes gene mutations as well as structural and numerical chromosome alterations. The group is aware of other mechanisms leading to carcinogenicity and other heritable diseases, but their identification requires additional types of mechanistic studies. ‘Genotoxicity’ refers to the capability of substances to damage DNA and/or cellular components regulating the fidelity of the genome—such as the spindle apparatus, topoisomerases, DNA repair systems and DNA polymerases (4)—and includes all adverse effects on genetic information. These potentially harmful effects on genetic material may be mediated directly or