Absorption and metabolism of 3-MCPD 1-monopalmitate in rats

Abstract

Fatty acid esters of 3-monochloropropane 1,2-diol (3-MCPD esters) are a group of potential chemical toxicants. Their toxic effects primarily include nephrotoxicity and hepatotoxicity. To understand the toxic mechanisms of 3-MCPD esters, one of the key points is to advance the understanding of their metabolic mechanisms in vivo. This dissertation investigated 1) the absorption and kinetics of 3-MCPD 1-monopalmitate in rats, 2) the possible metabolites of 3- MCPD 1-monopalmitate after oral administration to rats, and 3) the possible metabolic pathways of 3-MCPD 1-monopalmitate in vivo. The greatest concentration of 3-MCPD 1-monopalmitate in the plasma was 873.72 ng/mL (Cmax) at about 1.67 hours (Tmax) after oral administration. The concentration of 3-MCPD 1-monopalmitate reduced to half after 3.42 hours (t1/2). No 3-MCPD 1-monopalmitate could be detected after 4 hours, which was its mean resident time (MRT). The area under curve (AUC) for 3-MCPD 1-monopalmitate in rat plasma was 1676.15 h.ng/mL, which represented the maximum amount of 3-MCPD 1-monopalmitate absorbed into plasma under the testing conditions. Beside, 39 possible metabolites were tentatively identified in the liver, kidney, testis, brain, plasma and urine samples at 6, 12, 24 and 48 hours after oral administration of 3-MCPD 1-monopalmitate to rats. In addition, five major metabolic pathways of 3-MCPD esters were derivate to evaluate their metabolic conditions in vivo. These results can greatly enhance the understanding about the absorption, distribution and metabolism conditions of 3-MCPD esters in vivo, and promote further research about the biological actions of 3-MCPD esters.