Toxinology Research Group, Norwegian Veterinary Institute, Oslo, Norway.
Centre de la Recherche Nationale Scientifique, University of Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, 8 Allée du Général Rouvillois, 67000, Strasbourg, France.
Arch Toxicol. 2019 Jul;93(7):2087-2102. doi: 10.1007/s00204-019-02470-1. Epub 2019 May 7.
The mycotoxin deoxynivalenol (DON) has a high global prevalence in grain-based products. Biomarkers of exposure are detectable in most humans and farm animals. Considering the acute emetic and chronic anorexigenic toxicity of DON, maximum levels for food and feed have been implemented by food authorities. The tolerable daily intake (TDI) is 1 µg/kg body weight (bw)/day for the sum of DON and its main derivatives, which was based on the no-observed adverse-effect level (NOAEL) of 100 µg DON/kg bw/day for anorexic effects in rodents. Chronic exposure to a low-DON dose can, however, also cause inflammation and imbalanced neurotransmitter levels. In the present study, we therefore investigated the impact of a 2-week exposure at the NOAEL in mice by performing behavioural experiments, monitoring brain activation by c-Fos expression, and analysing changes in the metabolomes of brain and serum. We found that DON affected neuronal activity and innate behaviour in both male and female mice. Metabolite profiles were differentiable between control and treated mice. The behavioural changes evidenced at NOAEL reduce the safety margin to the established TDI and may be indicative of a risk for human health.
真菌毒素脱氧雪腐镰刀菌烯醇（DON）在谷物产品中有很高的全球流行率。暴露生物标志物在大多数人类和农场动物中都可检测到。考虑到 DON 的急性呕吐和慢性厌食毒性，食品当局已经为食品和饲料制定了最高限量。食品和饲料中 DON 及其主要衍生物的可耐受每日摄入量（TDI）为 1 µg/kg 体重（bw）/天，这是基于对啮齿动物的厌食作用的无观察到不良效应水平（NOAEL）100 µg DON/kg bw/天得出的。然而，慢性低剂量 DON 暴露也会引起炎症和神经递质水平失衡。在本研究中，我们通过行为实验、通过 c-Fos 表达监测大脑激活以及分析大脑和血清代谢组的变化，研究了在 NOAEL 下对小鼠进行 2 周暴露的影响。我们发现 DON 影响了雄性和雌性小鼠的神经元活动和先天行为。对照和处理组的小鼠之间可区分代谢物谱。在 NOAEL 下观察到的行为变化降低了对既定 TDI 的安全边际，可能表明对人类健康存在风险。
