Discussion

Genetic toxicology data have traditionally been used in a qualitative, binary manner (i.e., positive or negative) with little emphasis on the identification of no-effect levels or point of departure (PoD) values. This paradigm was based on the assumption that the dose-response for genotoxicity is linear with no “thresholds”. Furthermore, genotoxicity has not been used as an adverse apical endpoint itself, and has been primarily used to inform cancer risk assessment. However, in recent years, it is becoming increasingly apparent that the above paradigm is no longer justifiable and the genetic toxicology community should move away from qualitative hazard-based approaches to quantitative risk-based methodologies to facilitate data interpretation in the context of informing human risk. Here we review recent international efforts dealing with the quantitative evaluation of genotoxicity data to establish point of departure metrics. PoD metrics can be derived using various statistical modelling tools, and, using a set of potent genotoxicants as case studies, there has been recent consensus on which current metrics best model the genotoxic response. The benchmark dose approach is used widely in other areas of toxicology, and it is now time for the field of genetic toxicology to embrace this approach for human health risk assessment.