Applications and research progress of organ-on-a-chip and organoid-on-a-chip in the toxicity assessment of environmental pollutants

The growing health hazards posed by environmental pollutants have highlighted the urgent need to establish efficient and reliable toxicity assessment systems, which has become a key focus in toxicological research. Traditional toxicity evaluation primarily relies on animal testing and two-dimensional (2D) cell culture models. However, animal studies are limited by species-specific predictive biases and ethical controversies, while 2D cell models fail to accurately replicate human metabolic and toxicological responses due to their lack of three-dimensional microenvironments and intercellular interactions. To address these technical limitations, the development of novel in vitro evaluation models has become particularly crucial. In recent years, organ-on-a-chip (OoC) technology has demonstrated unique advantages in toxicological research by precisely simulating the physiological microenvironment and functional characteristics of human organs. Notably, organoid-on-a-chip technology, which integrates three-dimensional organoid culture systems with microfluidic platforms, has further enhanced the biomimetic performance and assessment accuracy of these models. This approach shows broad application prospects in drug toxicity testing, disease mechanism research, and environmental pollutant risk assessment. This review provides a systematic overview of the research progress in the application of organ-on-a-chip and organoid-on-a-chip technologies for toxicity assessment of typical environmental pollutants, including pesticides, endocrine-disrupting chemicals, microplastics/nanoplastics, and antibiotics. It focuses on summarizing their applications and advantages in studies of multi-organ interactions, metabolic toxicity, and endocrine-disrupting mechanisms. Furthermore, the challenges and future development prospects of these technologies in environmental toxicology and health risk assessment are discussed, with the aim of offering new technical support for the scientific assessment and regulatory decision-making related to emerging environmental pollutants.