Genotoxicity is defined as ‘agents or processes which alter the structure, information content, or segregation of DNA, including those which cause DNA damage by interfering with normal replication processes, or which in a non-physiological manner (temporarily) alter its replication’. Common mechanisms which result in genotoxicity include gene mutations or chromosomal aberrations.
Assessing the potential for genotoxicity is an important aspect of safety testing of pharmaceuticals (ICH S2 (R1)), chemicals (REACH, CLP/GHS, TSCA), pesticides (Plant Protection Products and Biocidal Products Regulations, FIFRA) and cosmetics (Cosmetics Regulation).
Genotoxicity testing is extensively used within the personal care and cosmetic industry to ensure safety of novel ingredients or formulations. The ban in animal testing for cosmetics in the EU, along with a push to reduce reliance on animal testing in other industries, has led to a focus in integrating in vitro methods into testing strategies. It is, however, recognised that no single in vitro assay can accurately predict genotoxic potential and, therefore, a combined approach using three in vitro methods is typically employed. Although each industry has different approaches, the most commonly used in vitro genotoxicity assays include:
Two out of three of the following mammalian tests for chromosomal damage:
- In vitro cell chromosomal aberration test
- In vitro mammalian micronucleus test
- In vitro mammalian cell gene mutation test (typically, the mouse lymphoma test)
According to some legislation (e.g., REACH, CLP, Cosmetics Regulation, TSCA, FIFRA), if negative in an in vitro battery of tests, a substance can be classified as non-genotoxic. However, in the case of safety testing of pharmaceuticals under ICH S2 (R1) and pesticides under the plant protection products regulation, animal testing is still relied upon to some extent as confirmation of the in vitro results.