Microplastics, nanoplastics, and plastic chemicals: applying the key characteristics of metabolism disrupting agents shows reason for concern

Abstract Objective This narrative review examines the potential role of plastic-derived chemicals and micro- and nanoplastics in metabolic diseases. It applies the recently proposed key characteristics (KCs) for metabolism-disrupting agents to evaluate chemicals commonly found in plastics and microplastic and nanoplastic particles. Methods The KC framework, adapted from the KCs of toxicants originally developed for the identification of carcinogens, was applied to evaluate evidence from epidemiological, animal, and cellular studies. The review specifically evaluates compounds such as perfluorooctanoic acid (PFOA), bisphenol-S (BPS), and diisonyl phthalate (DINP), as well as emerging evidence relating to microplastics and nanoplastics (MNPs). Results Evidence shows that exposure to chemicals derived from plastics, including PFOA, BPA substitutes (eg, BPS) and phthalate substitutes, is linked to metabolic dysfunction, obesity, diabetes, and MASLD. BPS and DINP exhibit properties consistent with metabolism-disrupting agents, suggesting they are “regrettable substitutes.” Although human data on MNPs are limited, animal and cellular studies indicate they may also contribute to metabolic diseases, though mechanisms remain unclear. Conclusion Rising exposure to chemicals in plastics poses significant risks to metabolic health. Identifying metabolic disruptors among thousands of plastic-associated chemicals is urgently needed. Increasing awareness and promoting the use of safer, inert, and reusable materials are essential steps to reduce health risks associated with plastic-derived pollutants and support more sustainable consumption.