Experimental methods for assessing biological effects of microplastics on mouse models: trends, gaps, and future directions

Abstract Microplastics (MPs) have emerged as pervasive environmental contaminants with the potential to induce adverse biological effects. Mouse models are widely used to evaluate MP toxicity, yet their translational value remains limited by methodological inconsistencies. This review critically examines studies from 2021 to 2025, focusing on five key parameters: sex, exposure route, particle characterization, concentration, and exposure duration. Sex-specific analyses are limited, restricting insight into differential susceptibility. While oral exposure best reflects human intake, non-oral routes remain prevalent and may distort risk estimates. Particle properties—size, shape, polymer type, and form—are often inconsistently described and frequently unrepresentative of environmental MPs, complicating cross-study comparisons and mechanistic interpretations. We highlight the importance of using environmentally relevant concentrations and chronic exposure durations to more accurately simulate real-world conditions. Despite growing efforts, inconsistencies in particle metrics and dose reporting formats continue to hinder data integration. To improve ecological and translational relevance, future MP toxicity studies should adopt standardized protocols, incorporate sex-balanced designs, and prioritize parameters that reflect actual human exposure scenarios.