The toxicity of 3-chloropropane-1,2-dipalmitate in Wistar rats and a metabonomics analysis of rat urine by ultra-performance liquid chromatography-mass spectrometry.
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| Abstract |
3-Monochloropropane-1,2-diol(3-MCPD) fatty acid esters can release free 3-MCPD in a certain condition. Free 3-MCPD is a well-known food contaminant and is toxicological well characterized, however, in contrast to free 3-MCPD, the toxicological characterization of 3-MCPD fatty acid esters is puzzling. In this study, toxicological and metabonomics studies of 3-chloropropane-1,2-dipalmitate(3-MCPD dipalmitate) were carried out based on an acute oral toxicity test, a 90-day feeding test and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis. The LD50 value of 3-MCPD dipalmitate was determined to be 1780 mg/kg body weight (bw) for Wistar rats. The results of the 90-day feeding test in male Wistar rats showed that 3-MCPD dipalmitate caused a significant increase in blood urea nitrogen and creatinine in the high-dose group (267 mg/kg bw/day) compared to control rats. Renal tubular epithelium cell degeneration and renal tubular hyaline cast accumulation were the major histopathological changes in rats administered 3-MCPD dipalmitate. Urine samples obtained after the 90-day feeding test and analyzed by UPLC-MS showed that the differences in metabolic profiles between control and treated rats were clearly distinguished by partial least squares-discriminant analysis (PLS-DA) of the chromatographic data. Five metabolite biomarkers which had earlier and significant variations had been identified, they were first considered to be the early, sensitive biomarkers in evaluating the effect of 3-MCPD dipalmitate exposure, and the possible mechanism of these biomarkers variation was elucidated. The combination of histopathological examination, clinical chemistry and metabolomics analyses in rats resulted in a systematic and comprehensive assessment of the long-term toxicity of 3-MCPD dipalmitate.
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| Authors | Jianshuang Li, Sen Wang, Maoqing Wang, Wenxiu Shi, Xiaoyan Du, Changhao Sun |
| Journal | Chemico-biological interactions (Chem Biol Interact) Vol. 206 Issue 2 Pg. 337-45 (Nov 25 2013) ISSN: 1872-7786 [Electronic] Ireland |
| PMID | 24140137 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2013 Elsevier Ireland Ltd. All rights reserved. |
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