Ninety-Day Subchronic Toxicology of Individual and Combined Toxicants from the Thermal Processing of Lipid-Rich Foods

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