2-hydroxybenzylamine (2-HOBA), a compound found in buckwheat, is a potent scavenger of reactive γ-ketoaldehydes, which are increased in diseases associated with inflammation and oxidative stress. While the potential of 2-HOBA is promising, studies were needed to characterize the safety of the compound before clinical trials. In a series of experiments, the risks of 2-HOBA-mediated mutagenicity and cardio-toxicity were assessed in vitro. The effects of 2-HOBA on the mRNA expression of select cytochrome P450 (CYP) enzymes were also assessed in cryopreserved human hepatocytes. Further, the distribution and metabolism of 2-HOBA in blood were determined. Our results indicate that 2-HOBA is not cytotoxic or mutagenic in vitro and does not induce the expression of CYP1A2, CYP2B6, or CYP3A4 in human hepatocytes. The results of the hERG testing showed a low risk of cardiac QT wave prolongation. Plasma protein binding and red blood cell distribution characteristics indicate low protein binding and no preferential distribution into erythrocytes. The major metabolites identified were salicylic acid and the glycoside conjugate of 2-HOBA. Together, these findings support development of 2-HOBA as a nutritional supplement and provide important information for the design of further preclinical safety studies in animals as well as for human clinical trials with 2-HOBA.

2-羟基苄胺（2-HOBA）是荞麦中的一种化合物，是一种有效的活性γ-酮醛清除剂，在与炎症和氧化应激相关的疾病中这种含量会增加。尽管2-HOBA的潜力令人鼓舞，但仍需要进行研究以表征该化合物在临床试验之前的安全性。在一系列实验中，在体外评估了2-HOBA介导的致突变性和心脏毒性的风险。还评估了2-HOBA对冷冻保存的人肝细胞中所选细胞色素P450（CYP）酶mRNA表达的影响。此外，测定了2-HOBA在血液中的分布和代谢。我们的结果表明2-HOBA在体外没有细胞毒性或致突变性，并且不诱导CYP1A2的表达，人肝细胞中的CYP2B6或CYP3A4。hERG测试结果显示心脏QT波延长的风险较低。血浆蛋白结合和红细胞分布特征表明蛋白结合低且没有优先进入红细胞的分布。鉴定出的主要代谢产物是水杨酸和2-HOBA的糖苷共轭物。这些发现共同支持了2-HOBA作为营养补品的开发，并为进一步的动物临床前安全性研究设计以及2-HOBA的人体临床试验提供了重要信息。