Epigenetic Effects of Bisphenol A Exposure: An Integrative Mechanistic Review with Critical Evaluation of Evidence Quality and Translational Gaps

Abstract

Bisphenol A (BPA) is an industrial chemical produced at large scale and commonly used in the manufacture of polycarbonate plastics, epoxy resins, and materials that come into contact with food. As a result, human exposure to BPA is widespread and continuous.In recent years, a growing body of research has suggested that many of BPA’s biological effects may be mediated through epigenetic processes. These processes influence gene activity without altering the underlying DNA sequence.Although several reviews have examined specific epigenetic pathways affected by BPA, most have not systematically evaluated the quality of evidence across different experimental models, considered how exposure levels compare with real-world human exposure, or clearly distinguished between intergenerational effects and true transgenerational inheritance.This review brings together current findings on BPA-related changes in three major epigenetic mechanisms: DNA methylation, histone modifications, and regulation of non-coding RNAs. The evidence is organized according to study type, including in vitro experiments, animal studies, and human epidemiological research, as well as by exposure level and developmental timing.We also outline a conceptual model linking receptor-mediated signaling to epigenetic alterations that may contribute to disease development. The strength of evidence varies across health outcomes: associations with metabolic disorders appear well supported, while links to reproductive and neurodevelopmental effects are moderately supported, and evidence for carcinogenic outcomes remains limited and preliminary.Several important challenges remain, including non-linear dose–response relationships at low exposure levels, the lack of reliable and accessible epigenetic biomarkers in human tissues, and uncertainty regarding whether these epigenetic changes can persist across multiple generations.Overall, this review provides a structured and evidence-based synthesis that can support future mechanistic research and inform the integration of epigenetic endpoints into regulatory risk assessment for BPA and related endocrine-disrupting chemicals