This Adverse Outcome Pathway (AOP) describes the linkage between oxidative DNA damage and irreversible genomic damage (chromosomal aberrations and mutations). DNA damage is considered an important contributor to the adverse health effects of many environmental toxicants and this AOP may thus be of widespread use to the regulatory community. Although increase in oxidative DNA damage is the molecular initiating event for this AOP, there are numerous upstream key events that can also lead to DNA oxidation. Thus, this AOP may be expanded upstream, and could be incorporated into a variety of AOP networks. Furthermore, the AOP points to critical research gaps required to establish the quantitative associations and modulating factors that connect KEs across the AOP, and highlights the utility of novel test methods in understanding and evaluating the implications of oxidative DNA damage. This AOP is referred to as AOP 296 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).