Mechanism-Based In Vitro Strategies to Assess the Toxicological Impact of Emerging Environmental and Pharmaceutical Contaminants

The increasing production and environmental dissemination of synthetic chemicals, including pharmaceuticals and emerging contaminants, raise important concerns regarding their potential effects on human health. Traditional toxicological assessments have historically relied on animal models. However, growing ethical considerations, regulatory pressure, and scientific advances have accelerated the development of human-relevant in vitro approaches. Modern in vitro toxicology increasingly focuses on mechanism-based investigations capable of identifying molecular and cellular pathways underlying adverse outcomes. Advanced cellular models, high-content screening, and omics-based techniques now allow researchers to evaluate complex toxicological endpoints such as endocrine disruption, immunotoxicity, and organ-specific toxicity. These developments align with the broader implementation of new approach methodologies (NAMs) aimed at improving predictive toxicology while reducing animal use. Consequently, mechanism-driven in vitro strategies represent a crucial component for understanding the biological impact of both environmental and pharmaceutical contaminants.This Research Topic aims to highlight innovative in vitro approaches designed to investigate the mechanistic basis of toxicity induced by emerging environmental and pharmaceutical contaminants. Despite significant progress in toxicological sciences, many chemicals currently present in the environment or used in consumer products and medicines remain insufficiently characterized in terms of their potential biological effects. Mechanism-based in vitro models provide powerful tools to address these knowledge gaps by enabling the identification of cellular pathways and molecular events associated with chemical exposure. The goal of this collection is to gather contributions that advance the development, validation, and application of human-relevant in vitro systems capable of elucidating toxicological mechanisms across diverse biological endpoints. Particular emphasis will be placed on studies that integrate mechanistic insights with modern toxicological frameworks, such as adverse outcome pathways (AOPs), high-throughput screening strategies, and multi-omics approaches. By bringing together contributions from researchers working across environmental, pharmaceutical, and mechanistic toxicology, this Research Topic seeks to foster interdisciplinary dialogue and promote innovative strategies for predictive and mechanistically informed hazard assessment.This Research Topic welcomes original research articles, reviews, mini-reviews, perspectives, and methodological papers describing mechanism-based in vitro approaches used to investigate the toxicological effects of environmental and pharmaceutical contaminants. Contributions may focus on the development or application of advanced cellular models, including primary human cells, stem-cell-derived systems, organoids, and microphysiological systems. Topics of interest include, but are not limited to: in vitro assessment of endocrine-disrupting chemicals; immunotoxicity and inflammatory responses; organ-specific toxicity such as liver, skin, lung, or barrier tissues; toxicological evaluation of emerging contaminants (e.g., PFAS, nanomaterials, microplastics, and pharmaceutical residues); high-throughput and high-content screening strategies; omics-based toxicology; and integration of in vitro data into adverse outcome pathway frameworks or risk assessment approaches. Studies addressing chemical mixtures, low-dose exposures, and innovative experimental platforms contributing to the advancement of human-relevant toxicology are particularly encouraged.Submissions that avoid the use of animal testing or animal-derived materials, including fetal bovine serum (FBS), will be especially encouraged. Authors are invited to adopt fully animal-free approaches that support more ethical, human-relevant, and innovative toxicology. Topic editors: Mirco Masi, Erica Buoso Source: https://www.frontiersin.org/research-topics/78557/mechanism-based-in-vitro-strategies-to-assess-the-toxicological-impact-of-emerging-environmental-and-pharmaceutical-contaminants