The toxicokinetic and toxic mechanisms of food thermal processing induced toxicants, 3-MCPD esters have been demonstrated in vivo. The absorptive and metabolic conditions of 3-MCPD esters in Sprague-Dawley (SD) rats has been clarified. The toxicology of 3-MCPD esters, especially the mechanisms of nephrotoxicity and testicular toxicity to SD rats were also determined by using proteomics, metabolomics and other technics. As the results, the metabolic parameters of 3-MCPD monopalmitate and dipalmitate, including the Cmax of 873.72 and 135.00 ng/mL, T1/2 of 3.42 and 3.87 h, Tmax of 1.67 and 2.50 h, MRT of 4.00 and 5.08 h, as well as the AUC0−∞ of 1676.15 and 458.47 h ng/mL have been determined. A total of 9 and 17 metabolites were tentatively identified from 3-MCPD mono- and di-palmitate, respectively. For the toxic mechanisms investigation, the proteomic analysis of kidney samples of SD rats after exposure of 3-MCPD esters showed deregulated proteins involved in the pathways for ion transportation, apoptosis, the metabolism of xenobiotics, and enzymes related to endogenous biological metabolisms, providing explanation for the nephrotoxicity of 3-MCPD esters. Testicular toxicity results indicating that 3-MCPD esters could activate RIPK1 and MLKL pathways, thus deregulated proteins related with the inflammatory necrosis pathways. These results showed that 3-MCPD esters could be absorbed and distributed to organs in their prototypes. And the toxic mechanisms of 3-MCPD esters in rats’ kidney and testes play a vital role in understanding the toxic effects of 3-MCPD esters, provide the scientific basis for the establishment of safety limits of 3-MCPD esters.

3-Monochloropropane 1,2-diol fatty acid esters: absorption, metabolism, nephrotoxicity and testicular toxicity in Sprague-Dawley rats

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ACS Fall 2022

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