Influence of non-degradable and degradable microplastics on the bioavailability of per- and polyfluoroalkyl substance in mice: Mechanism exploration

Per- and polyfluorinated alkyl substances (PFAS) contamination in drinking water and their associated health risks have received extensive global attention. Microplastics (MPs), which commonly coexist with PFAS in the daily diet, remain poorly understood in terms of their effects on PFAS bioavailability. Here, we investigated the effect of non-biodegradable (PS) and biodegradable (PBS) MPs on PFAS bioavailability using a mouse model, with PFAS level in drinking water being at 20 μg/L. High-dose dietary MPs (50 mg/g) significantly increased PFAS bioavailability, especially for PS co-exposure (29.2 ± 5.09 % vs 19.4 ± 3.66 % in control, p < 0.05), while reducing fecal excretion by 0.34 and 0.31-fold (p < 0.05). Mechanistic studies showed that high-dose PS significantly (p < 0.05) increased mouse serum albumin concentrations, which were closely related with the in vivo absorption of PFAS. Both PS and PBS downregulated the expression of efflux proteins (Mrp2 and Mrp4) by 0.10–0.22 fold, thereby increasing PFAS bioavailability. Molecular docking further showed that legacy PFASs (PFOA and PFOS) exhibited higher binding affinities to transport-related proteins than emerging alternatives (HFPO-TA and 6:2 FTSA), explaining their greater susceptibility to MPs co-exposure. These findings provide novel mechanistic insights into the modulation of PFAS bioavailability by co-exposure of MPs. While high MP doses were used to elucidate the mechanism, future studies using environmentally relevant exposure levels are necessary to assess the health risks of PFAS-MP co-exposure and support science-based risk management.