Flufenacet Metabolites in Wheat Show Reverse Distribution and Elevated Toxicity: Challenging Conventional Risk Assessment of PFAS-Classified Pesticides.

Amid increasing concerns over fluorinated compounds, the Organization for Economic Co-operation and Development (OECD) has reclassified numerous fluorinated pesticides as per- and polyfluoroalkyl substances (PFAS), yet their metabolite distribution in plants remains unexplored. Using flufenacet as a model compound, this study investigated the metabolic distribution in wheat. We discovered a "reverse distribution" phenomenon where the parent compound mainly concentrated in roots (translocation factor = 0.08), while metabolites preferentially accumulated in shoots. The three metabolites with the highest shoot responses, M07, M10, and M15, showed TF values of 1.54, 2.37, and 1.67, respectively. This pattern challenges traditional lipophilicity-based transport theories and increases food chain exposure risks. Toxicity assessment revealed that despite lower acute toxicity, these metabolites exhibited higher hepatotoxicity, mutagenicity, and carcinogenicity than the parent compound, with M10 showing higher carcinogenic potential. Molecular docking demonstrated binding to human proteins with energies of -6.01 to -7.34 kcal/mol. Findings suggest revising risk assessment frameworks to incorporate metabolite distribution and toxicological properties for PFAS pesticide management.