van der Zande Meike, Vandebriel Rob J, Groot Maria J, Kramer Evelien, Herrera Rivera Zahira E, Rasmussen Kirsten, Ossenkoppele Jan S, Tromp Peter, Gremmer Eric R, Peters Ruud J B, Hendriksen Peter J, Marvin Hans J P, Hoogenboom Ron L A P, Peijnenburg Ad A C M, Bouwmeester Hans
RIKILT - Wageningen University & Research Centre, 6700 AE Wageningen, The Netherlands.
Part Fibre Toxicol. 2014 Feb 7;11:8. doi: 10.1186/1743-8977-11-8.
Synthetic Amorphous Silica (SAS) is commonly used in food and drugs. Recently, a consumer intake of silica from food was estimated at 9.4 mg/kg bw/day, of which 1.8 mg/kg bw/day was estimated to be in the nano-size range. Food products containing SAS have been shown to contain silica in the nanometer size range (i.e. 5-200 nm) up to 43% of the total silica content. Concerns have been raised about the possible adverse effects of chronic exposure to nanostructured silica.
Rats were orally exposed to 100, 1000 or 2500 mg/kg bw/day of SAS, or to 100, 500 or 1000 mg/kg bw/day of NM-202 (a representative nanostructured silica for OECD testing) for 28 days, or to the highest dose of SAS or NM-202 for 84 days.
SAS and NM-202 were extensively characterized as pristine materials, but also in the feed matrix and gut content of the animals, and after in vitro digestion. The latter indicated that the intestinal content of the mid/high-dose groups had stronger gel-like properties than the low-dose groups, implying low gelation and high bioaccessibility of silica in the human intestine at realistic consumer exposure levels. Exposure to SAS or NM-202 did not result in clearly elevated tissue silica levels after 28-days of exposure. However, after 84-days of exposure to SAS, but not to NM-202, silica accumulated in the spleen. Biochemical and immunological markers in blood and isolated cells did not indicate toxicity, but histopathological analysis, showed an increased incidence of liver fibrosis after 84-days of exposure, which only reached significance in the NM-202 treated animals. This observation was accompanied by a moderate, but significant increase in the expression of fibrosis-related genes in liver samples.
Although only few adverse effects were observed, additional studies are warranted to further evaluate the biological relevance of observed fibrosis in liver and possible accumulation of silica in the spleen in the NM-202 and SAS exposed animals respectively. In these studies, dose-effect relations should be studied at lower dosages, more representative of the current exposure of consumers, since only the highest dosages were used for the present 84-day exposure study.
合成无定形二氧化硅（SAS）常用于食品和药品中。最近，估计消费者从食物中摄入的二氧化硅为9.4毫克/千克体重/天，其中估计有1.8毫克/千克体重/天处于纳米尺寸范围。已证明含有SAS的食品中纳米尺寸范围（即5 - 200纳米）的二氧化硅含量高达总二氧化硅含量的43%。人们对长期接触纳米结构二氧化硅可能产生的不良影响表示担忧。
大鼠经口暴露于100、1000或2500毫克/千克体重/天的SAS，或100、500或1000毫克/千克体重/天的NM - 202（一种经合组织测试用的代表性纳米结构二氧化硅），持续28天，或暴露于SAS或NM - 202的最高剂量，持续84天。
SAS和NM - 202作为原始材料得到了广泛表征，同时也对动物饲料基质、肠道内容物以及体外消化后的情况进行了表征。后者表明，中/高剂量组的肠道内容物比低剂量组具有更强的凝胶样特性，这意味着在实际消费者暴露水平下，二氧化硅在人体肠道中的凝胶化程度低且生物可及性高。暴露于SAS或NM - 202 28天后，组织二氧化硅水平未明显升高。然而，暴露于SAS 84天后，而非NM - 202，二氧化硅在脾脏中蓄积。血液和分离细胞中的生化和免疫标志物未显示毒性，但组织病理学分析表明，暴露84天后肝纤维化发生率增加，这仅在接受NM - 202处理的动物中具有统计学意义。这一观察结果伴随着肝脏样本中纤维化相关基因表达的适度但显著增加。
尽管仅观察到少数不良影响，但仍有必要进行进一步研究，以分别进一步评估在暴露于NM - 202和SAS的动物中观察到的肝脏纤维化的生物学相关性以及二氧化硅在脾脏中可能的蓄积情况。在这些研究中，应在更低剂量下研究剂量 - 效应关系，这些剂量更能代表当前消费者的暴露情况，因为在本次84天暴露研究中仅使用了最高剂量。
