The interface of epigenetics and toxicology in product safety assessment

Abstract

Recent advancements in science and technology have exponentially increased our understanding of epigenetics, and it is important to examine these advancements in the context of potential benefits to safety assessments of chemical products. Product safety assessment is an essential component of product development and is applied to both “new” and “existing” chemical products. The current human health safety assessment paradigm consists of characterizing dose responses for adverse apical outcomes across a multitude of toxicology studies to identify a point of departure (POD) and does not typically include the characterization of genomic or epigenomic changes. Given the fundamental mechanistic intersection of molecular (e.g. epigenetic) and apical changes, it would be anticipated that an adverse apical outcome identified in a regulatory guideline study would be preceded by an epigenetic change. While epigenetics is not currently being utilized in regulatory risk assessments to date, there is promising potential to improve future risk assessment strategies by incorporating epigenetic endpoints. For example, epigenetic endpoints could be used as biomarkers of traditional adverse apical effects or incorporated into adverse outcome pathways (AOPs) or benchmark dose (BMD) approaches to identify a POD. In this manuscript, the role of epigenomic changes in the context of human product safety assessment is examined.