Chapter 7. In Vitro Genotoxicity

Abstract

In vitro genotoxicity testing has played an important role in the safety assessment of chemicals, pharmaceuticals, cosmetic ingredients and environmental pollutants since the mid-1970s. This testing allows for an early look into the possible genetic hazards of a material before expensive animal testing is needed or prior to clinical trials. In vitro genetic toxicology can identify mutations and chromosome damage which may be progenitors of carcinogenesis. Standard regulatory assays are low-throughput, have a high compound requirements and are time consuming. In recent years, industry has identified the need to support early, rapid safety assessment of most chemicals to reduce attrition, costs and to comply with the initiatives to reduce, refine or replace animal testing (3Rs). To improve such screening, higher throughput assays have been developed to help with chemical compound selection and to build up structure–activity relationships. In parallel, these assays have been developed with a better understanding of the nature of the genotoxicity observed and to complement the risk assessment process. Finally, 30 years later, new technologies and initiatives are helping researchers further understand the nature of genetic damage, the role of epigenetic changes in carcinogenesis and, through multi-disciplinary high-throughput collaborations, how genotoxicity fits into toxicity ‘signatures’ or ‘fingerprints’ of thousands of compounds to create better risk prediction models.