Sharma A K, Mortensen A, Schmidt B, Frandsen H, Hadrup N, Larsen E H, Binderup M-L
Technical University of Denmark, National Food Institute, Division of Toxicology & Risk Assessment, Mørkhøj Bygade 19, 2860 Søborg, Denmark.
Technical University of Denmark, National Food Institute, Division of Toxicology & Risk Assessment, Mørkhøj Bygade 19, 2860 Søborg, Denmark.
Mutat Res Genet Toxicol Environ Mutagen. 2014 Aug;770:66-71. doi: 10.1016/j.mrgentox.2014.04.023. Epub 2014 Jun 2.
Because of the increasing use of clays and organoclays in industrial applications it is of importance to consider the toxicity of these materials. Recently it was reported that the commercially available Montmorillonite clay, Cloisite(®) 30B, which is surface-modified by organic quaternary ammonium compounds, was genotoxic in vitro. In the present study the in-vivo genotoxic and inflammatory potential of Cloisite(®) 30B was investigated as a follow-up of the in-vitro studies. Wistar rats were exposed to Cloisite(®) 30B twice 24h apart by oral gavage, at doses ranging from 250 to 1000 mg/kg body weight [indicate duration of treatment; Ed.]. There was no induction of DNA strand-breaks in colon, liver and kidney cells and there was no increase in inflammatory cytokine markers in blood-plasma samples. In order to verify the possible absorption of Cloisite(®) 30B from the gastrointestinal tract, inductively coupled plasma mass-spectrometry (ICP-MS) analysis was performed on samples of liver, kidney and faeces, with aluminium as a tracer element characteristic to clay. The results showed that aluminium could be detected in faeces, but not in the liver or kidneys. This indicated that there was no systemic exposure to clay particles from Cloisite(®) 30B. Detection and identification of free quaternary ammonium modifier in the highest dose of Cloisite(®) 30B was carried out by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). This analysis revealed a mixture of three quaternary ammonium analogues. The detected concentration of the organomodifier corresponded to an exposure of rats to about 5mg quaternary ammonium analogues/kg body weight.
由于粘土和有机粘土在工业应用中的使用日益增加，考虑这些材料的毒性具有重要意义。最近有报道称，市售的经有机季铵化合物表面改性的蒙脱石粘土Cloisite(®) 30B在体外具有遗传毒性。在本研究中，作为体外研究的后续，对Cloisite(®) 30B的体内遗传毒性和炎症潜力进行了研究。将Wistar大鼠通过口服灌胃，以250至1000 mg/kg体重的剂量，每隔24小时暴露于Cloisite(®) 30B两次[注明治疗持续时间；编者注]。在结肠、肝脏和肾脏细胞中未诱导DNA链断裂，血浆样本中的炎症细胞因子标志物也未增加。为了验证Cloisite(®) 30B是否可能从胃肠道吸收，以铝作为粘土特有的示踪元素，对肝脏、肾脏和粪便样本进行了电感耦合等离子体质谱(ICP-MS)分析。结果表明，铝可在粪便中检测到，但在肝脏或肾脏中未检测到。这表明没有来自Cloisite(®) 30B的粘土颗粒的全身暴露。通过高效液相色谱与四极杆飞行时间质谱联用(HPLC-Q-TOF-MS)对最高剂量的Cloisite(®) 30B中的游离季铵改性剂进行了检测和鉴定。该分析揭示了三种季铵类似物的混合物。检测到的有机改性剂浓度相当于大鼠暴露于约5mg季铵类似物/kg体重。
