Fungicide co-exposure influences ibuprofen accumulation, distribution and phytotoxicological responses in zucchini (Cucurbita pepo).

Pharmaceuticals introduced into agricultural soils through wastewater reuse and biosolids application may coexist with crop-protection products, yet the influence of fungicides on pharmaceutical uptake and phytotoxicity in crops remains poorly understood. This study investigated how benomyl, chlorothalonil, validamycin A, and probenazole affect ibuprofen (IBU) accumulation, translocation, and physiological responses in zucchini (Cucurbita pepo cv. Soraya). IBU accumulated mainly in roots, and its distribution depended on fungicide identity. Compared with IBU alone, root accumulation was numerically higher under benomyl and significantly higher under validamycin A. Root-to-leaf translocation factors varied among treatments, but these differences were not statistically significant. These findings indicate treatment-dependent effects of fungicide co-exposure on IBU accumulation, particularly in roots, while evidence for differential root-to-leaf translocation remains inconclusive. Ibuprofen alone caused only minor physiological changes, whereas co-exposure, particularly with benomyl and chlorothalonil, reduced biomass and photosynthetic pigment concentrations and altered antioxidant and detoxification responses. The IBU+B treatment was associated with the highest lipid peroxidation. Molecular docking predicted a computationally plausible interaction between IBU and CpMLP-SY1, with AutoDock Vina scores ranging from -6.8 to -6.6 kcal mol-1. Metabolic disturbances were strongest in roots and were dominated by amino acid biosynthesis and metabolism, particularly pathways involving branched-chain, aromatic and sulfur-containing amino acids, with additional alterations in secondary metabolism. These results indicate that fungicide co-exposure can influence IBU accumulation and plant responses in a treatment-dependent manner.