Microplastics–PFAS interactions in environmental matrices: quantitative evidence for antagonistic and synergistic toxicity

Microplastics (MPs) and per- and polyfluoroalkyl substances (PFAS) increasingly co-occur across aquatic, terrestrial, and biological systems, yet their combined toxicological behavior remains poorly resolved. To address this gap, we conducted a systematic review and meta-analysis of 47 controlled experimental studies encompassing aquatic organisms, soil invertebrates, and mammalian models. Using standardized mean differences (Hedges’ g) under a random-effects REML framework, supported by subgroup analysis, meta-regression, and bias diagnostics, we quantitatively compared biological responses induced by MPs, PFAS, and their co-exposure. PFAS produced the strongest and most consistent toxic effects across systems (g = 4.71; 95% CI: 2.32–7.09), with pronounced impacts on oxidative balance, hepatic function, immune regulation, and reproductive performance. MPs also induced widespread biological stress, though with lower and more variable intensity (g = 2.19; 95% CI: −0.29–4.66), affecting oxidative, reproductive, and inflammatory pathways. Notably, co-exposure to MPs and PFAS frequently resulted in attenuated or antagonistic responses rather than additive toxicity (g = −2.98; 95% CI: −8.89–2.93), suggesting that PFAS adsorption onto MP surfaces can reduce bioavailability and tissue uptake. However, synergistic effects emerged under specific conditions, particularly at high PFAS concentrations, with small or weathered particles and prolonged exposure durations. Dose response relationships were evident across exposure categories, with aquatic species displaying the greatest sensitivity. Overall, these findings demonstrate that mixture toxicity is context-dependent and cannot be inferred from single-compound data alone. This study provides a quantitative foundation for advancing mixture-aware environmental risk assessment and regulatory frameworks.