AbstractInorganic arsenic (iAs) poses a major threat to worldwide human health, and yet the molecular mecha-nisms underlying the toxic effects associated with iAs ex-posure are not well understood. There is increasing exper-imental evidence indicating that epigenetic modifications may play a major role in the development of diseases associated with exposure to environmental toxicants. Re-search in the field has firmly established that iAs exposure is associated with epigenetic alterations including changes in DNA methylation, miRNA abundance, and post-translational histone modifications. Here, we summarize recent studies that have expanded the current knowledge of these relationships. These studies have pinpointed spe-cific regions of the genome and genes that are targets of arsenical-induced epigenetic changes, including those as-sociated within utero iAs exposure. The recent literature indicates that iAs biotransformation likely plays an impor-tant role in the relationship between iAs exposure and the
epigenome, in addition to the sex and genetic background of individuals. The research also shows that relatively low to moderate exposure to iAs is associated with epigenetic effects. However, while it is well established that arsenicals
can alter components of the epigenome, in many cases, the biological significance of these alterations remains un-known. The manner by which these and future studies may help inform the role of epigenetic modifications in the development of iAs-associated disease is evaluated and the need for functional validation emphasized. Keywords Arsenic.DNAmethylation.Histone post-translational modifications. MicroRNAs.Epigenetic reprogramming .Prenatal exposure.Epigenome