Long-Term Health Effects and Underlying Biological Mechanisms of Developmental Exposure to Arsenic

Lisa Smeester, Rebecca C. Fry

Exposure to inorganic arsenic (iAs) via drinking water represents a significant global public health threat with chronic exposure associated with cancer, skin lesions, neurological impairment, and cardiovascular diseases. Particularly susceptible populations include the developing fetus and young children. This review summarizes some of the critical studies of the long-term health effects and underlying biological mechanisms related to developmental exposure to arsenic. It also highlights the complex factors, such as the sex of the exposed individual, that contribute to susceptibility to the later life health effects of iAs. Studies in animal models, as well as human population-based studies, have established that prenatal and early life iAs exposures are associated with long-term effects, and many of these effects display sexually dimorphic responses. As an underlying molecular basis, recent epidemiologic and toxicologic studies have demonstrated that changes to the epigenome may play a key mechanistic role underlying many of the iAs-associated health outcomes. Developmental exposure to iAs results in early and later life health effects. Mechanisms underlying these outcomes are likely complex, and include disrupted key biological pathways with ties to the epigenome. This highlights the importance of continued research, particularly in animal models, to elucidate the important underpinnings (e.g., timing of exposure, metabolism, dose) of these complex health outcomes and to identify the biological mechanisms underlying sexual dimorphism in iAs-associated diseases. Future research should investigate preventative strategies for the protection from the detrimental health endpoints associated with early life exposure to iAs. Such strategies could include potential interventions focused on dietary supplementation for example the adoption of a folate-rich diet.