Chloropropanols are chemical contaminants that can be formed during industrial processing of foods, such as lipids used in commercially available infant and toddler formula in the USA. Many researchers have studied the most common chloropropanol contaminant, 3-monochloropropane-1,2-diol (3-MCPD), as well as its lipid ester derivatives. A plethora of toxicological outcomes have been described in vivo, including effects on the heart, nervous system, reproductive organs, and kidneys. To better understand the concordance of some of these effects to in vitro outcomes, we focused our research on using an in vitro cellular model to investigate whether the proximal tubule cells of the kidney would be vulnerable to the effects of free 3-MCPD and nine of its common esters in commercial formula. Using the established human kidney proximal tubule cell line, HK-2, we performed 24-h treatments using 3-MCPD and nine mono- or di-esters derived from palmitate, oleate, and linoleate. By directly exposing HK-2 cells at treatment doses ranging from 0 to 100 μM, we could evaluate their effects on cell viability, mitochondrial health, reactive oxygen species (ROS) production, and other endpoints of toxicity. Since chloropropanols reportedly inhibit cellular metabolism through interference with glycolysis, we also tested the extent of this mechanism. Overall, we found mild but statistically significant evidence of cytotoxicity at the highest tested treatment concentrations, which were also associated with mitochondrial dysfunction and transient perturbations in cellular metabolism. Based on these findings, further studies will be required to better understand the effects of these compounds under conditions that are more physiologically relevant to human infant and toddler proximal tubules in order to mimic their exposure to chloropropanol-containing foods.

中文翻译：

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游离 3-MCPD 和选择 3-MCPD 酯对人近端小管 HK-2 细胞的体外毒理学评估。

氯丙醇是在食品工业加工过程中可能形成的化学污染物，例如美国市售婴幼儿配方奶粉中使用的脂质。许多研究人员研究了最常见的氯丙醇污染物 3-monochloropropane-1,2-diol (3-MCPD) 及其脂质酯衍生物。体内已经描述了过多的毒理学结果，包括对心脏、神经系统、生殖器官和肾脏的影响。为了更好地了解其中一些影响与体外结果的一致性，我们将研究重点放在使用体外细胞模型来研究肾脏的近端小管细胞是否容易受到游离 3-MCPD 和 9其在商业配方中的常见酯。使用已建立的人肾近端小管细胞系，HK-2，我们使用 3-MCPD 和九种源自棕榈酸酯、油酸酯和亚油酸酯的单酯或二酯进行 24 小时处理。通过以 0 到 100 μM 的治疗剂量直接暴露 HK-2 细胞，我们可以评估它们对细胞活力、线粒体健康、活性氧 (ROS) 产生和其他毒性终点的影响。由于据报道氯丙醇通过干扰糖酵解来抑制细胞代谢，我们还测试了这种机制的程度。总体而言，我们在最高测试处理浓度下发现了轻微但具有统计学意义的细胞毒性证据，这也与线粒体功能障碍和细胞代谢的短暂扰动有关。基于这些发现，