Urinary non-targeted toxicokinetics and metabolic fingerprinting of exposure to 3-monochloropropane-1,2-diol and glycidol from refined edible oils

Abstract

The widespread presence of 3-monochloropropane-1,2-diol (3-MCPD) and glycidol in refined edible oils have raised food industrial and public health concerns, but their specific biomarkers of exposure and urinary metabolic pathways indicating nephrotoxicity remain largely unknown. Here, we unraveled the in vivo biotransformation of these two contaminants and revealed how they affect metabolic pathways in rats. Urine metabolomes in rats administered with glycidol or 3-MCPD were investigated using ultra-high performance liquid chromatography combined with a quadrupole-orbitrap high-resolution mass spectrometry. Compared to the currently acknowledged metabolite which is only 2,3-dihydroxypropyl mercapturic acid, we identified 8 and 4 new specific exposure biomarkers of glycidol and 3-MCPD, respectively, via mapping the glyceryl polymerization and glutathione and sulfur conjugation. The changes of metabolites in the surrounding metabolic network were investigated to further gain insight into their metabolic fates. Exposure to glycidol up-regulated citrate, isocitrate, ketoglutarate, malate, and pyruvate in the tricarboxylic acid cycle and glycolysis pathways, while 3-MCPD intake down-regulated these signal molecules in both pathways. Nonetheless, L-cysteine, proline, and arginine were significantly decreased by the effect of either glycidol or 3-MCPD. Our findings first map the urinary metabolomics of both contaminants from edible oils and advance the omics-level recognition for their observational health hazards.