Department Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
Arch Toxicol. 2017 Sep;91(9):3145-3155. doi: 10.1007/s00204-016-1927-0. Epub 2017 Jan 30.
The chlorinated propanols 2- and 3-monochloropropanediol (MCPD), and their fatty acid esters have gained public attention due to their frequent occurrence as heat-induced food contaminants. Toxic properties of 3-MCPD in kidney and testis have extensively been characterized. Other 3-MCPD target organs include heart and liver, while 2-MCPD toxicity has been observed in striated muscle, heart, kidney, and liver. Inhibition of glycolysis appears to be important in 3-MCPD toxicity, whereas mechanisms of 2-MCPD toxicity are still unknown. It is thus not clear whether toxicity by the two isomeric compounds is dependent on similar or dissimilar modes of action. A 28-day oral feeding study in rats was conducted using daily non-toxic doses of 2-MCPD or 3-MCPD [10 mg/kg body weight], or an equimolar (53 mg/kg body weight) or a lower (13.3 mg/kg body weight) dose of 2-MCPD dipalmitate. Comprehensive comparative proteomic analyses of substance-induced alterations in the common target organ heart revealed striking similarities between effects induced by 2-MCPD and its dipalmitate ester, whereas the degree of effect overlap between 2-MCPD and 3-MCPD was much less. The present data demonstrate that even if exerting effects in the same organ and targeting similar metabolic networks, profound differences between molecular effects of 2-MCPD and 3-MCPD exist thus warranting the necessity of separate risk assessment for the two substances. This study for the first time provides molecular insight into molecular details of 2-MCPD toxicity. Furthermore, for the first time, molecular data on 3-MCPD toxicity in the heart are presented.
氯丙醇 2-和 3-单氯丙二醇（MCPD）及其脂肪酸酯由于其作为热诱导食品污染物的频繁出现而引起了公众的关注。3-MCPD 在肾脏和睾丸中的毒性已得到广泛研究。其他 3-MCPD 靶器官包括心脏和肝脏，而 2-MCPD 毒性已在横纹肌、心脏、肾脏和肝脏中观察到。抑制糖酵解似乎在 3-MCPD 毒性中很重要，而 2-MCPD 毒性的机制仍不清楚。因此，不清楚两种同分异构体化合物的毒性是否依赖于相似或不同的作用模式。在大鼠中进行了为期 28 天的口服喂养研究，使用每日非毒性剂量的 2-MCPD 或 3-MCPD[10mg/kg 体重]，或等摩尔（53mg/kg 体重）或较低剂量（13.3mg/kg 体重）的 2-MCPD 二棕榈酸酯。对共同靶器官心脏中物质诱导的改变进行综合比较蛋白质组学分析，发现 2-MCPD 与其二棕榈酸酯诱导的作用之间存在惊人的相似性，而 2-MCPD 和 3-MCPD 之间的作用重叠程度要小得多。本研究数据表明，即使在同一器官中发挥作用并针对相似的代谢网络，2-MCPD 和 3-MCPD 的分子效应之间也存在明显差异，因此有必要对这两种物质进行单独的风险评估。这项研究首次为 2-MCPD 毒性的分子细节提供了分子见解。此外，首次提出了心脏中 3-MCPD 毒性的分子数据。
