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Bioaccessibility, bioavailability and toxicity of commercially relevant iron- and chromium-based particles: in vitro studies with an inhalation perspective

机译:商业上相关的铁和铬基颗粒的生物可及性,生物利用度和毒性:具有吸入角度的体外研究

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Background Production of ferrochromium alloys (FeCr), master alloys for stainless steel manufacture, involves casting and crushing processes where particles inevitably become airborne and potentially inhaled. The aim of this study was to assess potential health hazards induced by inhalation of different well-characterized iron- and chromium-based particles, i.e. ferrochromium (FeCr), ferrosiliconchromium (FeSiCr), stainless steel (316L), iron (Fe), chromium (Cr), and chromium(III)oxide (Cr2O3), in different size fractions using in vitro methods. This was done by assessing the extent and speciation of released metals in synthetic biological medium and by analyzing particle reactivity and toxicity towards cultured human lung cells (A549). Results The amount of released metals normalized to the particle surface area increased with decreasing particle size for all alloy particles, whereas the opposite situation was valid for particles of the pure metals. These effects were evident in artificial lysosomal fluid (ALF) of pH 4.5 containing complexing agents, but not in neutral or weakly alkaline biological media. Chromium, iron and nickel were released to very low extent from all alloy particles, and from particles of Cr due to the presence of a Cr(III)-rich protective surface oxide. Released elements were neither proportional to the bulk nor to the surface composition after the investigated 168 hours of exposure. Due to a surface oxide with less protective properties, significantly more iron was released from pure iron particles compared with the alloys. Cr was predominantly released as Cr(III) from all particles investigated and was strongly complexed by organic species of ALF. Cr2O3 particles showed hemolytic activity, but none of the alloy particles did. Fine-sized particles of stainless steel caused however DNA damage, measured with the comet assay after 4 h exposure. None of the particles revealed any significant cytotoxicity in terms of cell death after 24 h exposure. Conclusion It is evident that particle and alloy characteristics such as particle size and surface composition are important aspects to consider when assessing particle toxicity and metal release from alloy particles compared to pure metal particles. Generated results clearly elucidate that neither the low released concentrations of metals primarily as a result of protective and poorly soluble surface oxides, nor non-bioavailable chromium complexes, nor the particles themselves of occupational relevance induced significant acute toxic response, with exception of DNA damage from stainless steel.
机译:背景技术铬铁合金(FeCr)是用于不锈钢制造的中间合金,其生产涉及铸造和压碎工艺,其中颗粒不可避免地会悬浮在空气中并可能被吸入。这项研究的目的是评估吸入不同特征的铁和铬基颗粒(即铬铁(FeCr),硅铁铬(FeSiCr),不锈钢(316L),铁(Fe),铬)可能引起的潜在健康危害。 (Cr)和氧化铬(III)(Cr 2 O 3 ),在使用体外方法分离不同大小的部分。通过评估合成生物介质中释放的金属的程度和形态,并通过分析颗粒对培养的人肺细胞的反应性和毒性(A549)来完成这一工作。结果对于所有合金颗粒,归一化为颗粒表面积的释放金属的量随颗粒尺寸的减小而增加,而相反的情况对于纯金属颗粒是有效的。在含有络合剂的pH 4.5的人工溶酶体液(ALF)中,这些作用是明显的,但在中性或弱碱性的生物介质中则不明显。由于存在富含Cr(III)的保护性表面氧化物,所有合金颗粒以及Cr颗粒中铬,铁和镍的释放量非常低。在研究的168小时暴露后,释放的元素既与体积不成正比,也不与表面组成成正比。由于表面氧化物的保护性较差,因此与合金相比,从纯铁颗粒中释放出的铁明显更多。 Cr主要从所有研究的颗粒中以Cr(III)的形式释放,并被ALF的有机物强烈络合。 Cr 2 O 3 颗粒具有溶血活性,但合金颗粒均没有。然而,细小尺寸的不锈钢颗粒会引起DNA损伤,这是在暴露4小时后用彗星试验测定的。就暴露于24小时后的细胞死亡而言,没有一个颗粒显示出任何明显的细胞毒性。结论显然,与纯金属颗粒相比,评估合金颗粒的颗粒毒性和金属释放时,颗粒和合金的特性(例如颗粒大小和表面组成)是重要的考虑因素。产生的结果清楚地表明,主要由于保护性和难溶性表面氧化物而导致的低浓度金属释放,非生物利用性铬络合物的释放,以及与职业相关的颗粒本身均未引起显着的急性毒性反应,但DNA的DNA损伤除外不锈钢。

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