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致热合成无定形二氧化硅(NM-203):亚慢性经口暴露后对大鼠的遗传毒性。

Pyrogenic synthetic amorphous silica (NM-203): Genotoxicity in rats following sub-chronic oral exposure.

作者信息

Villani Paola, Eleuteri Patrizia, Pacchierotti Francesca, Maranghi Francesca, Tassinari Roberta, Narciso Laura, Tait Sabrina, Lori Gabriele, Andreoli Cristina, Huet Sylvie, Jarry Gérard, Fessard Valérie, Cordelli Eugenia

机构信息

Division of Health Protection Technology, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Rome, Italy.

Center for Gender-Specific Medicine, Istituto Superiore di Sanità (ISS), Rome, Italy.

出版信息

Mutat Res Genet Toxicol Environ Mutagen. 2022 Apr-May;876-877:503458. doi: 10.1016/j.mrgentox.2022.503458. Epub 2022 Jan 24.

DOI:10.1016/j.mrgentox.2022.503458
PMID:35483783
Abstract

The genotoxicity of nano-structured synthetic amorphous silica (SAS), a common food additive, was investigated in vivo in rats. A 90-day oral toxicity study was performed according to OECD test guideline 408 and the genotoxicity of pyrogenic SAS nanomaterial NM-203 was assessed in several organs, using complementary tests. Adult Sprague-Dawley rats of both sexes were treated orally for 90 days with 0, 2, 5, 10, 20, or 50 mg SAS/kg bw per day. Dose levels were selected to approximate expected human dietary exposures to SAS. DNA strand breaks were evaluated by the comet assay in blood, bone marrow, liver, and spleen according to OECD test guideline 489; mutations induced in bone marrow precursors of erythrocytes were assessed by the Pig-a assay and chromosome/ genome damage by the micronucleus assay in blood (OECD test guideline 474) and colon. No treatment-related increases of gene (Pig-a) or chromosome/genome (micronucleus) mutations were detected in the blood. The percentage of micronucleated cells was not increased in the colon of treated rats. Among the organs analyzed by the comet assay, the spleen was the only target showing a weak but biologically relevant genotoxic effect.

摘要

对常见食品添加剂纳米结构合成无定形二氧化硅(SAS)的遗传毒性进行了大鼠体内研究。根据经合组织测试指南408进行了为期90天的口服毒性研究,并使用补充试验评估了热解法SAS纳米材料NM - 203在多个器官中的遗传毒性。成年雌雄Sprague-Dawley大鼠每天经口给予0、2、5、10、20或50毫克SAS/千克体重,持续90天。选择剂量水平以近似预期人类饮食中对SAS的暴露量。根据经合组织测试指南489,通过彗星试验评估血液、骨髓、肝脏和脾脏中的DNA链断裂;通过Pig-a试验评估红细胞骨髓前体细胞中诱导的突变,并通过血液(经合组织测试指南474)和结肠中的微核试验评估染色体/基因组损伤。在血液中未检测到与处理相关的基因(Pig-a)或染色体/基因组(微核)突变增加。处理大鼠的结肠中微核细胞百分比未增加。在通过彗星试验分析的器官中,脾脏是唯一显示出微弱但具有生物学相关性的遗传毒性效应的靶器官。

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Pyrogenic synthetic amorphous silica (NM-203): Genotoxicity in rats following sub-chronic oral exposure.致热合成无定形二氧化硅(NM-203):亚慢性经口暴露后对大鼠的遗传毒性。
Mutat Res Genet Toxicol Environ Mutagen. 2022 Apr-May;876-877:503458. doi: 10.1016/j.mrgentox.2022.503458. Epub 2022 Jan 24.
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