title: 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.
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.
authors.affiliation: Public Health College, Harbin Medical University, Harbin 150081, PR China; College of Medical Laboratory Science and Technology, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, PR China.
authors.forename: Jianshuang
authors.initials: J
authors.lastname: Li
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.forename: Maoqing
authors.initials: M
authors.lastname: Wang
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Shi
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Du
authors.forename: Changhao
authors.initials: C
authors.lastname: Sun
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D016002:Discriminant Analysis; D005990:Glycerol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity / Q000652:urine; D007684:Kidney Tubules / Q000473:pathology; D016018:Least-Squares Analysis; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D051381:Rats; D017208:Rats, Wistar; D000517:alpha-Chlorohydrin
chemical_list: D000517:alpha-Chlorohydrin; D003404:Creatinine; D005990:Glycerol
keywords: 3-Chloropropane-1,2-dipalmitate; 3-MCPD; 3-MPCD dipalmitate; 3-chloropropane-1,2-dipalmitate; 3-monochloropropane-1,2-diol; ALT; AST; BPI; BUN; Cr; ESI-TOF-MS; HE; IDO; LD(50); MS; Metabonomics; PCA; PLS-DA; RT; TDI; Toxicity; UPLC; UPLC–MS; VIP; Variable Importance in the Project; acid-HVP; acid-hydrolyzed vegetable proteins; alanine aminotransferase; aspartate aminotransferase; base peak intensity; blood urea nitrogen; creatinine; electrospray ionization time-of-flight mass spectrometry; hematoxylin–eosin; indolamine-2,3-dioxygenase; mass spectrometry; median lethal dose; partial least squares discriminant analysis; principal component analysis; retention time; tolerable daily intake; ultra performance liquid chromatography