Toxicoepigenomics: Epigenetic disruption by environmental exposures and implications for biomarker development

Environmental exposures are increasingly recognized as key modulators of the epigenome, contributing to both immediate and long-term disease risk. The field of toxicoepigenomics, which investigates how environmental toxicants alter epigenetic regulation, has demonstrated that exposures to endocrine-disrupting chemicals, heavy metals, polycyclic aromatic hydrocarbons (PAHs), and air pollutants can disrupt gene expression through changes in DNA methylation, histone modifications, non-coding RNA expression, and higher-order chromatin structure. Additionally, lifestyle factors—including diet, physical activity, stress, and sleep—interact with these exposures to shape individual epigenetic profiles and influence health trajectories across the lifespan. This review synthesizes current evidence across major pollutant classes and molecular pathways, emphasizing both well-characterized and emerging mechanisms. Retained introns represent post-transcriptional consequences of chromatin-based epigenetic regulation and serve as sensitive indicators of environmentally induced disruptions in transcriptional elongation and splicing fidelity. We also highlight recent advances in high-throughput technologies, including whole-genome bisulfite sequencing, single-cell epigenomics, and epigenetic clock models, which are rapidly enhancing biomarker discovery and mechanistic understanding. By integrating multilayered epigenetic insights across diverse exposure contexts, this review advances the field of toxicoepigenomics and lays the groundwork for developing robust, exposure-responsive biomarkers of environmental disease. These insights offer significant promise for guiding mechanistic research, improving exposure surveillance, and informing the design of precision strategies in environmental health. • Environmental toxicants induce multilayered epigenetic alterations. • DNA methylation, histone marks, and ncRNAs are affected by real-world exposures. • Retained introns emerge as novel epigenetic signatures of toxicant response. • Epigenetic dysregulation links exposures to long-term health risks. • Epigenomic markers show promise for hazard assessment and biomonitoring.