Influence of microplastics on bisphenol A and bisphenol AF toxicity in aquatic environments: Mechanistic insights for environmental risks.

Co-exposure to low-density polyethylene microplastics (LDPE-MPs) and plastic additives like bisphenol A (BPA) and bisphenol AF (BPAF) poses a growing concern in aquatic environments, yet the role of LDPE-MPs in modulating their toxicity remains debated. This study integrates transcriptome sequencing, adsorption/desorption kinetics, and computational toxicology to assess how LDPE-MPs influence BPA- and BPAF-induced toxicity in zebrafish. We found that BPAF is more toxic than BPA, with 96 h lethal concentration 50 % (LC) values of 1.659 mg/L for BPAF and 6.219 mg/L for BPA. LDPE-MPs act as dual modulators, alleviating or exacerbating toxicity in a chemical- and pathway-dependent manner. For BPA, LDPE-MPs mitigate its impact on phototransduction by adsorbing BPA, reducing its bioavailability, and preserving light signal conversion. In contrast, LDPE-MPs exacerbate BPA-induced nucleotide metabolism disruptions by enhancing inosine-5'-monophosphate dehydrogenase (IMPDH) activity, leading to increased gene transcription and accumulation of metabolic intermediates. For BPAF, LDPE-MPs alleviate glucose metabolism disruptions by enhancing ligand-receptor interactions, restoring glucose homeostasis. However, LDPE-MPs have little effect on BPAF-induced upregulation of steroid biosynthesis genes. These findings highlight the integration of multi-omics approaches (transcriptome sequencing, adsorption/desorption kinetics, and computational toxicology) to reveal the dual mechanisms of LDPE-MPs, addressing the knowledge gap in understanding pathway-specific toxicity mechanisms in existing studies. The results emphasize the necessity of prioritizing regulatory control of BPAF and integrating BPA/BPAF-MPs interactions into future pathway-based environmental risk assessment frameworks.