German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
School of Medicine, Jacqui Wood Cancer Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK.
Food Chem Toxicol. 2020 Aug;142:111459. doi: 10.1016/j.fct.2020.111459. Epub 2020 May 29.
2-Monochloropropane-1,3-diol (2-MCPD) and its isomer 3-monochloropropane-1,2-diol (3-MCPD) are widespread food contaminants. 3-MCPD has been classified as a non-genotoxic carcinogen, whereas very limited toxicological data are available for 2-MCPD. Animal studies indicate that heart and skeletal muscle are target organs of 2-MCPD. Oxidative stress may play a role in this process, and the potential of 3-MCPD to induce oxidative stress in vivo has already been demonstrated. To investigate the potential of 2-MCPD to induce oxidative stress in vivo, a 28-day oral feeding study in male HOTT reporter mice was conducted. This mouse model allows monitoring substance-induced oxidative stress in various target organs on the basis of Hmox1 promoter activation. Repeated daily doses of up to 100 mg 2-MCPD/kg body weight did not result in substantial toxicity. Furthermore, the highest dose of 2-MCPD had only minor effects on oxidative stress in kidney and testes, whereas brain, heart and skeletal muscle were not affected. Additionally, 2-MCPD caused only mild changes in the expression of Nrf2-dependent genes and only slightly affected the redox status of the redox-sensor protein DJ-1. Thus, the data indicate that 2-MCPD, in contrast to its isomer 3-MCPD, does not lead to a considerable induction of oxidative stress in male mice.
2-氯-1,3-丙二醇（2-MCPD）及其异构体 3-氯-1,2-丙二醇（3-MCPD）是广泛存在的食品污染物。3-MCPD 已被归类为非遗传毒性致癌物质，而 2-MCPD 的毒理学数据非常有限。动物研究表明，心脏和骨骼肌是 2-MCPD 的靶器官。氧化应激可能在此过程中发挥作用，并且已经证明 3-MCPD 具有在体内诱导氧化应激的潜力。为了研究 2-MCPD 在体内诱导氧化应激的潜力，对雄性 HOTT 报告小鼠进行了为期 28 天的口服喂养研究。这种小鼠模型允许基于 Hmox1 启动子激活来监测各种靶器官中物质诱导的氧化应激。重复每日高达 100mg 2-MCPD/kg 体重的剂量不会导致实质性毒性。此外，2-MCPD 的最高剂量仅对肾脏和睾丸中的氧化应激产生轻微影响，而对大脑、心脏和骨骼肌没有影响。此外，2-MCPD 仅导致 Nrf2 依赖性基因的表达发生轻度变化，并且仅略微影响氧化还原敏感蛋白 DJ-1 的氧化还原状态。因此，数据表明，2-MCPD 与异构体 3-MCPD 相反，不会导致雄性小鼠体内氧化应激的大量诱导。
