S12-04 Developments and potential applications of epigenetic tools for chemical hazard assessment

Abstract

Epigenetic modulations underlie critical developmental processes that contribute to determining adult phenotypes (physiological outcomes). They involve a series of mechanisms that entail histone and DNA covalent modifications and non-coding RNAs, which collectively contribute to programming cell functions and differentiation. Epigenetic anomalies and DNA mutations are co-drivers of cellular dysfunction pathways, from endocrine disruption (Greally and Jacobs 2013, Jacobs et al. 2017), to metabolic and immune disruption and ultimately carcinogenesis (Jacobs et al. 2020, Desaulniers et al. 2021, Louekari and Jacobs 2024). Test methods that can be adapted to measure and monitor key epigenetic marks in response to toxicant exposure could already be providing a valuable tool for predicting adverse health outcomes. However the evidence basis for regulatory purposes needs to be translated from in vivo to in vitro and strengthened experimentally. Furthermore, how such tests could be combined into and be interpreted by integrated approaches for testing and assessment of chemicals needs to be clearly described to assist test method developers, regulators and policy makers. These considerations will be discussed, with examples, in my presentation.