Epigenotoxicity: Decoding the epigenetic imprints of genotoxic agents and their implications for regulatory genetic toxicology.

Regulatory genetic toxicology focuses on DNA damage and subsequent gene mutations. However, genotoxic agents can also affect epigenetic marks, and incorporation of epigenetic data into the regulatory framework may thus enhance the accuracy of risk assessment. Additionally, epigenetic alterations may identify non-genotoxic carcinogens that are not captured with the current battery of tests. Epigenetic alterations could also explain long-term consequences and potential transgenerational effects in the absence of DNA mutations. Therefore, at the 2022 International Workshops on Genotoxicity Testing (IWGT) in Ottawa (Ontario, Canada), an expert workgroup explored whether including epigenetic endpoints would improve regulatory genetic toxicology. Here we summarize the presentations and the discussions on technical advancements in assessing epigenetics, how the assessment of epigenetics can enhance strategies for detecting genotoxic and non-genotoxic carcinogens and the correlation between epigenetic alterations with other relevant apical endpoints.