Material-specific modulation of microplastic biotoxicity by chlorination: Mechanistic insights into ER stress and associated health risks.

Chlorination, a widely used disinfection method in drinking water treatment plants, poses underexplored health risks through its interactions with microplastics (MPs). Here, we show that chlorination induces significant physicochemical changes in four common MPs-polyethylene (PE), polyurethane (PU), polytetrafluoroethylene (PTFE), and polymethyl methacrylate (PMMA)-focusing on particles smaller than 30 µm. PU and PE MPs exhibit the most pronounced changes including significant surface degradation and oxidation, releasing various organic compounds. In vitro assays show that disinfected PU MPs significantly increased cytotoxicity, while disinfected PE MPs mitigated toxicity by modulating ER stress via the IRE1α/XBP1/BIP pathway. In vivo, 30-day exposure to pristine PE and disinfected PU MPs induce tissue damage, inflammation, and immune responses. Transcriptomic analysis of Liver revealed disrupted lipid, glutathione, and iron metabolism, activating DNA replication and proteasome pathways linked to ER stress. mRNA validation confirmed that disinfected MPs induces toxicity via the PERK/EIF2α/ATF4 pathway, with disinfected PU MPs causing severe damage, with significant CHOP upregulation indicating apoptosis. These findings underscore the biotoxicological impacts of disinfected MPs and provide insights for optimizing disinfection methods and mitigating the health risks of MPs in water treatment, particularly given the widespread use of chlorination worldwide.