title: Hepatotoxicity and nephrotoxicity induced by the chlorpyrifos and chlorpyrifos-methyl metabolite, 3,5,6-trichloro-2-pyridinol, in orally exposed mice.
abstract: 3,5,6-Trichloro-2-pyridinol (TCP) is a primary degradation product of chlorpyrifos and chlorpyrifos-methyl. TCP has longer half-life in soil and greater solubility in water than its parent compound, and cause wide contamination in environments. However, studies about the toxic effects of TCP are limited and outdate. In this study, 5 mg/kg/day, 50 mg/kg/day, and 150 mg/kg/day TCP were given to male mice through gavage for four weeks. As a result, the final body weights of TCP treated groups were significantly lower than control, and the relative organ weights of the liver and kidney were significantly higher than that of control. In addition, NMR-based metabolomics was used to investigate the toxic effects of TCP. It was found that a total of 39 serum metabolites were significantly changed in the TCP-treated groups, and these metabolites are related to hepatotoxicity and nephrotoxicity. These results were also confirmed by histopathology, serum biochemical, and oxidative stress analysis. In addition, metabolic disturbances due to TCP exposure were also observed based on altered metabolites. As far as we know, these results are the first to show the metabolomic toxicity of TCP, which warrants further research.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China. Electronic address: yanzhang@nju.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Geography Science, Nanjing Normal University, Jiangsu 210023, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China. Electronic address: hqren@nju.edu.cn.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Ren
mesh_terms: D000818:Animals; D004390:Chlorpyrifos / Q000031:analogs & derivatives / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D011728:Pyridones / Q000633:toxicity*
chemical_list: D007306:Insecticides; D011728:Pyridones; C012587:3,5,6-trichloro-2-pyridinol; D004390:Chlorpyrifos; C007031:chlorpyrifos-methyl
keywords: 3,5,6-Trichloro-2-pyridinol; Metabolomics; Mice; Organophosphorus insecticides; Subchronic effects