Ninety-Day Subchronic\nToxicology of Individual and\nCombined Toxicants from the Thermal Processing of Lipid-Rich Foods

Oxidative derivatives of triacylglycerols (ox-TGs), aldehydes,\nand 3-monochloropropane-1,2-diol esters (3-MCPDE) were simultaneously\nevaluated in a 90-day subchronic study, focusing on biological indicators,\nbiochemical indicators, and serum metabolomics as the first part of\nintegrated toxicity and interactions. After 90 days of feeding Kunming\nmice, coexposure to combined toxicants significantly inhibited the\ntrend of liver weight gain, reduced the levels of total bilirubin\n(TBIL) and direct bilirubin (DBIL), and decreased uric acid (UA) compared\nto individual toxicant exposure. A total of 21 and 31 biomarkers in\nfemale and male mice were identified, respectively. Co-exposure to\ncombined toxicants might mitigate the changes in cytidine, CDP, dUMP,\nand dUDP involved in purine and pyrimidine metabolism caused by a\nsingle exposure, but exacerbate the changes in l-tryptophan,\n5-hydroxy-l-tryptophan, and 5-hydroxyindoleacetic acid, which\nare involved in tryptophan metabolism. These results provided new\ninsights into a comprehensive toxicity and interaction evaluation\nmodel of multiple combined toxicants in food.