This study investigates the individual and combined effects of the mycotoxins, Aflatoxin B1 (AFB1), Enniatin B (ENNB) and Sterigmatocystin (STG), on the cellular viability of gastric (NCI–N87), intestinal (Caco-2), hepatic (Hep-G2) and renal (Hek-293) cells, shedding light on synergistic or antagonistic effects using a constant ratio combination design proposed by Chou-Talalay. These toxins are prevalent in cereal-based foods, frequently consumed by children which raises concerns about their exposure to these mycotoxins. This population is particularly vulnerable to the effects of these toxins due to their underdeveloped organs and incompletely structured physiological processes. Results showed that ENB was the most toxic of the three mycotoxins across all cell lines, while STG and AFB1 showed lower toxicity. The combination of ENNB + STG was found to be the most potent in terms of binary mixtures. In regard to ternary combinations, Caco-2 cells are more sensitive to the tested mycotoxins, whereas NCI–N87 cells show lower levels of cell damage. Worrying dose reduction values (>10-fold) were found for ENNB in binary and ternary combinations at low exposure levels. These findings are significant for establishing initial reference values, which play a pivotal role in estimating reference doses that are subsequently incorporated into the broader risk assessment process.

中文翻译：

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研究同时存在的黄曲霉毒素 B1、恩尼亚汀 B 和杂色曲霉素对胃、肠、肝和肾细胞模型的单独和混合物细胞毒性

本研究调查了霉菌毒素、黄曲霉毒素 B1 (AFB1)、恩尼亚汀 B (ENNB) 和杂色曲霉素 (STG) 对胃 (NCI-N87)、肠 (Caco-2)、肝 (Caco-2) 细胞活力的单独和联合影响。 Hep-G2）和肾（Hek-293）细胞，使用 Chou-Talalay 提出的恒定比例组合设计揭示了协同或拮抗作用。这些毒素普遍存在于谷物食品中，儿童经常食用这些食品，这引起了人们对他们接触这些霉菌毒素的担忧。由于器官发育不全和生理过程不完整，该人群特别容易受到这些毒素的影响。结果表明，ENB 是所有细胞系中三种霉菌毒素中毒性最强的，而 STG 和 AFB1 的毒性较低。就二元混合物而言，ENNB + STG 的组合被发现是最有效的。对于三元组合，Caco-2 细胞对测试的霉菌毒素更敏感，而 NCI-N87 细胞显示出较低水平的细胞损伤。在低暴露水平下，二元和三元组合中的 ENNB 的剂量减少值令人担忧（>10 倍）。这些发现对于建立初始参考值具有重要意义，初始参考值在估计随后纳入更广泛的风险评估过程的参考剂量方面发挥着关键作用。