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应用 OECD 指南 423 评估单端孢霉烯族毒素的急性经口毒性。

Application of OECD Guideline 423 in assessing the acute oral toxicity of moniliformin.

机构信息

Finnish Food Safety Authority, Chemistry and Toxicology Research Unit, Finland.

出版信息

Food Chem Toxicol. 2013 Mar;53:27-32. doi: 10.1016/j.fct.2012.11.023. Epub 2012 Nov 28.

Abstract

Moniliformin is a Fusarium mycotoxin highly prevalent in grains and grain-based products worldwide. In this study, the acute oral toxicity of moniliformin was assessed in Sprague-Dawley male rats according to OECD Guideline 423 with a single-dose exposure. Clinical observations and histopathological changes were recorded together with the excretion of moniliformin via urine and feces, utilizing a novel liquid chromatography-mass spectrometry method. According to our study, moniliformin is acutely toxic to rats with a rather narrow range of toxicity. Moniliformin can be classified into category 2 (LD(50) cut-off value 25 mg/kg b.w.), according to the Globally Harmonized System for the classification of chemicals. The clinical observations included muscular weakness, respiratory distress and heart muscle damage. Pathological findings confirmed that heart is the main target tissue of acute moniliformin toxicity. A significant proportion (about 38%) of the administered moniliformin was rapidly excreted in urine in less than 6 h. However, the toxicokinetics of the majority of the administered dose still requires clarification, as the total excretion was only close to 42%. Considering the worldwide occurrence of moniliformin together with its high acute toxicity, research into the subchronic toxicity is of vital importance to identify the possible risk in human/animal health.

摘要

展青霉素是一种在世界范围内普遍存在于谷物和谷物制品中的镰刀菌真菌毒素。在这项研究中,根据 OECD 指南 423 采用单次剂量暴露法,对雄性 Sprague-Dawley 大鼠进行了展青霉素的急性经口毒性评估。同时记录了临床观察和组织病理学变化,以及利用新型液相色谱-质谱法检测展青霉素在尿液和粪便中的排泄情况。根据我们的研究,展青霉素对大鼠具有较高的急性毒性,且毒性范围较窄。根据全球化学品统一分类和标签制度,展青霉素可被归类为 2 类(LD50 截止值 25mg/kg bw)。临床观察包括肌肉无力、呼吸困难和心肌损伤。病理发现证实,心脏是急性展青霉素毒性的主要靶组织。约 38%的给予剂量的展青霉素在不到 6 小时内迅速通过尿液排泄。然而,大部分给予剂量的毒代动力学仍需进一步阐明,因为总排泄量仅接近 42%。考虑到展青霉素在世界范围内的普遍存在及其高急性毒性,对其亚慢性毒性的研究对于确定其对人类/动物健康的潜在风险至关重要。

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