Department of Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
Arch Toxicol. 2017 Sep;91(9):3157-3174. doi: 10.1007/s00204-016-1924-3. Epub 2017 Jan 16.
Numerous Maillard reaction and lipid oxidation products are present in processed foods such as heated cereals, roasted meat, refined oils, coffee, and juices. Due to the lack of experimental toxicological data, risk assessment is hardly possible for most of these compounds. In the present study, an in silico approach was employed for the prediction of the toxicological endpoints mutagenicity and carcinogenicity on the basis of the structure of the respective compound, to examine (quantitative) structure-activity relationships for more than 800 compounds. Five software tools for mutagenicity prediction (T.E.S.T., SARpy, CAESAR, Benigni-Bossa, and LAZAR) and three carcinogenicity prediction tools (CAESAR, Benigni-Bossa, and LAZAR) were combined to yield so-called mutagenic or carcinogenic scores for every single substance. Alcohols, ketones, acids, lactones, and esters were predicted to be mutagenic and carcinogenic with low probability, whereas the software tools tended to predict a considerable mutagenic and carcinogenic potential for thiazoles. To verify the in silico predictions for the endpoint mutagenicity experimentally, twelve selected compounds were examined for their mutagenic potential using two different validated in vitro test systems, the bacterial reverse mutation assay (Ames test) and the in vitro micronucleus assay. There was a good correlation between the results of the Ames test and the in silico predictions. However, in the case of the micronucleus assay, at least three substances, 2-amino-6-methylpyridine, 6-heptenoic acid, and 2-methylphenol, were clearly positive although they were predicted to be non-mutagenic. Thus, software tools for mutagenicity prediction are suitable for prioritization among large numbers of substances, but these predictions still need experimental verification.
许多美拉德反应和脂质氧化产物存在于加工食品中，如加热的谷类食品、烤肉、精炼油、咖啡和果汁。由于缺乏实验毒理学数据，大多数这些化合物的风险评估几乎是不可能的。在本研究中，基于各自化合物的结构，采用计算方法预测了毒理学终点致突变性和致癌性，以检查 800 多种化合物的（定量）构效关系。使用了 5 种致突变性预测软件工具（T.E.S.T.、SARpy、CAESAR、Benigni-Bossa 和 LAZAR）和 3 种致癌性预测工具（CAESAR、Benigni-Bossa 和 LAZAR），对每一种单一物质的致突变性或致癌性进行评分。醇、酮、酸、内酯和酯被预测为具有低概率的致突变性和致癌性，而软件工具倾向于预测噻唑具有相当大的致突变性和致癌性。为了验证终点致突变性的计算预测的实验结果，使用两种不同的经过验证的体外测试系统，即细菌回复突变试验（Ames 试验）和体外微核试验，对 12 种选定的化合物的致突变潜力进行了检查。Ames 试验的结果与计算预测之间存在良好的相关性。然而，在微核试验中，至少有三种物质，即 2-氨基-6-甲基吡啶、6-庚烯酸和 2-甲基苯酚，尽管被预测为非致突变性，但却是明显阳性的。因此，致突变性预测软件工具适用于大量物质的优先级排序，但这些预测仍需要实验验证。
