Evaluation and interpretation of chemical genotoxicity risks; Strategies for method development

Chemical toxicity is a major health concern. Extensive efforts have been made to reduce human exposure to harmful substances and genotoxicity is evaluated as one component of the overall human-safety assessment of chemicals. Many toxicology tests are conducted on experimental animals (in vivo) or cell lines (in vitro). The outcomes of these tests are extrapolated to assess hazards to humans. Many in vitro genotoxicity assays have been developed for hazard identification; however, the field is undergoing a significant shift from hazard identification toward risk assessment. Also, strategies are shifting from reliance on empirical in vivo and in vitro data toward the identification of toxicity mechanisms. Thus, new approaches are being explored to improve our understanding of genotoxicity mechanisms and their relevance in humans. The determination of genotoxic risk thresholds, in relation to cancer risk, is critical for human safety assessment. Risks should be neither overestimated nor underestimated. It is also necessary to consider the balance between risks and benefits of specific chemical substances.