Comprehensive review of in vitro approaches for environmental heavy metal exposure

Abstract Heavy metals are ubiquitous environmental pollutants, contaminating air, soil, and water via the erosion of natural deposits, as well as originating from anthropogenic sources, such as agriculture, industries, transportation, and landfills. The increasing utilization of heavy metals over the years, combined with the persistent nature of metals in the environment poses a direct threat to human and environment health. Although regulatory limits have been established for toxic metals, assessing the associated health risks using real-life exposure scenarios remains challenging. In this review, we summarize the development and use of in vitro models based two- and three-dimensional cell culture systems, focusing on exposure to heavy metals via the dermal, inhalation, and ingestion routes using environmental samples. We also highlight recent developments in three-dimensional cell culture techniques and their potential for implementation in evaluating environmental samples for heavy metal toxicity. In addition, we assess the comparative strengths and specific applications of different modeling approaches, emphasizing the value of integrating advanced in vitro systems in environmental toxicology.