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Lung inflammation and lack of genotoxicity in the comet and micronucleus assays of industrial multiwalled carbon nanotubes Graphistrength(©) C100 after a 90-day nose-only inhalation exposure of rats.
Particle and Fibre Toxicology ( IF 7.2 ) Pub Date : 2015-07-10 , DOI: 10.1186/s12989-015-0096-2
Daniela Pothmann 1 , Sophie Simar 2 , Detlef Schuler 1 , Eva Dony 3 , Stéphane Gaering 1 , Jean-Loïc Le Net 4 , Yoshi Okazaki 5 , Jean Michel Chabagno 6 , Cécile Bessibes 6 , Julien Beausoleil 6 , Fabrice Nesslany 2, 7 , Jean-François Régnier 8
Affiliation  

Graphistrength © C100 multiwalled carbon nanotubes (MWCNT) provide superior electrical and mechanical properties for various applications. The evaluation of the intrinsic hazard properties of Graphistrength© C100 is an essential step for safe use. A general feature of multiwalled carbon nanotubes after inhalation or intratracheal exposures is the induction of an inflammatory reaction in the lungs sometimes associated with local genotoxic effects. After investigating different parameters for the aerosol generation and performing a 5-day inhalation range finding study, male and female Wistar rats were exposed nose-only for 90 days to target concentrations of 0.05, 0.25 and 5.0 mg/m3 air of Graphistrength © C100 and sacrificed 24 h and 90 days after the last exposure. Broncho-alveolar lavage fluid (BALF) was also collected and analyzed for inflammatory parameters. Twenty-four hours post-exposure, chromosomal aberrations in the bone marrow cells were evaluated by the micronucleus test and DNA damages in the lung, kidney and liver cells by both the standard and the human 8-oxoguanine DNA N-glycosylase 1 (hOGG1)-modified comet assay. All studies were performed according to the OECD test guidelines. An inflammatory lung reaction and the release of inflammatory factors in the BALF were observed in all rats exposed to 5.0 mg/m3, associated with changes in the differential white blood cells counts. The slight changes in BALF parameters at 0.25 mg/m3 recovered and signs of lung clearance of the MWCNT were observed. No pathological changes were observed on the pleura. Neither increase in the number of micronucleated polychromatic erythrocytes nor increase in percent DNA damage were observed at any concentration. Lung inflammation characteristic of an overload with insoluble particles was observed after a 90-day exposure to 5.0 mg/m3 of Graphistrength © C100. Clear signs of clearance and recovery were observed at 0.25 mg/m3. No genotoxicity was detected locally in lung and distally in bone marrow, liver and kidney. Therefore, Graphistrength © C100 appears of low concern in term of local and systemic genotoxicity and a No-Observed Adverse Effect Concentration (NOAEC) of 0.25 mg/m3 (0.28 mg/m3 as actual concentration) was established for the repeated-dose toxicity.

中文翻译:

在仅吸入鼻子90天的工业多壁碳纳米管Graphistrength(©)C100的彗星和微核试验中,肺部炎症和缺乏遗传毒性。

Graphistrength©C100多壁碳纳米管(MWCNT)为各种应用提供卓越的电气和机械性能。对Graphistrength©C100的固有危险特性进行评估是安全使用的必不可少的步骤。吸入或气管内暴露后,多壁碳纳米管的一般特征是诱发肺部炎症反应,有时与局部遗传毒性作用有关。在研究了不同的气溶胶生成参数并进行了5天的吸气范围发现研究后,雄性和雌性Wistar大鼠仅通过鼻子暴露90天,目标浓度为Graphistrength©C100和0.05、0.25和5.0 mg / m3的空气。在最后一次暴露后24小时90天处死。还收集了支气管肺泡灌洗液(BALF)并分析了炎症参数。暴露后二十四小时,通过微核试验评估骨髓细胞中的染色体畸变,并通过标准和人8-氧代鸟嘌呤DNA N-糖基化酶1(hOGG1)评估肺,肾和肝细胞中的DNA损伤。改良的彗星测定。所有研究均根据OECD测试指南进行。在所有暴露于5.0 mg / m3的大鼠中均观察到BALF中有炎症性肺反应和炎症因子的释放,这与白细胞计数的差异有关。在0.25 mg / m3时,BALF参数的轻微变化得以恢复,并且观察到MWCNT的肺部清除迹象。在胸膜上未观察到病理变化。在任何浓度下,均未观察到微核多色红细胞数量的增加或DNA损伤百分数的增加。在暴露于5.0 mg / m3 Graphistrength©C100的90天后,观察到不溶性颗粒超负荷引起的肺部炎症特征。在0.25 mg / m3的浓度下观察到明显的清除和回收迹象。在肺部和远端,骨髓,肝和肾中均未检测到遗传毒性。因此,就局部和全身遗传毒性而言,Graphistrength©C100受到的关注较少,针对重复剂量毒性,未观察到的不良反应浓度(NOAEC)为0.25 mg / m3(实际浓度为0.28 mg / m3)。
更新日期:2015-07-10
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