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

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          Abstract

          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 (Cr 2O 3), 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. Cr 2O 3 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.

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          Most cited references32

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          Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes.

          Since the manufacture and use of nanoparticles are increasing, humans are more likely to be exposed occupationally or via consumer products and the environment. However, so far toxicity data for most manufactured nanoparticles are limited. The aim of this study was to investigate and compare different nanoparticles and nanotubes regarding cytotoxicity and ability to cause DNA damage and oxidative stress. The study was focused on different metal oxide particles (CuO, TiO2, ZnO, CuZnFe2O4, Fe3O4, Fe2O3), and the toxicity was compared to that of carbon nanoparticles and multiwalled carbon nanotubes (MWCNT). The human lung epithelial cell line A549 was exposed to the particles, and cytotoxicity was analyzed using trypan blue staining. DNA damage and oxidative lesions were determined using the comet assay, and intracellular production of reactive oxygen species (ROS) was measured using the oxidation-sensitive fluoroprobe 2',7'-dichlorofluorescin diacetate (DCFH-DA). The results showed that there was a high variation among different nanoparticles concerning their ability to cause toxic effects. CuO nanoparticles were most potent regarding cytotoxicity and DNA damage. The toxicity was likely not explained by Cu ions released to the cell medium. These particles also caused oxidative lesions and were the only particles that induced an almost significant increase (p = 0.058) in intracellular ROS. ZnO showed effects on cell viability as well as DNA damage, whereas the TiO2 particles (a mix of rutile and anatase) only caused DNA damage. For iron oxide particles (Fe3O4, Fe2O3), no or low toxicity was observed, but CuZnFe2O4 particles were rather potent in inducing DNA lesions. Finally, the carbon nanotubes showed cytotoxic effects and caused DNA damage in the lowest dose tested. The effects were not explained by soluble metal impurities. In conclusion, this study highlights the in vitro toxicity of CuO nanoparticles.
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            Size-dependent toxicity of metal oxide particles--a comparison between nano- and micrometer size.

            Toxicological studies have shown increased toxicity of nanoparticles (<100 nm) compared to micrometer particles of the same composition, which has raised concern about the impact on human health from nanoparticles. However, if this is true for a wide range of particles with different chemical composition is not clear. The aim of this study was to compare the toxicity of nano- and micrometer particles of some metal oxides (Fe(2)O(3), Fe(3)O(4), TiO(2) and CuO). The ability of the particles to cause cell death, mitochondrial damage, DNA damage and oxidative DNA lesions were evaluated after exposure of the human cell line A549. This study showed that nanoparticles of CuO were much more toxic compared to CuO micrometer particles. One key mechanism may be the ability of CuO to damage the mitochondria. In contrast, the micrometer particles of TiO(2) caused more DNA damage compared to the nanoparticles, which is likely explained by the crystal structures. The iron oxides showed low toxicity and no clear difference between the different particle sizes. In conclusion, nanoparticles are not always more toxic than micrometer particles, but the high toxicity of CuO nanoparticles shows that the nanolevel gives rise to specific concern.
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              Particle Morphology and Density Characterization by Combined Mobility and Aerodynamic Diameter Measurements. Part 1: Theory

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                Author and article information

                Journal
                Part Fibre Toxicol
                Particle and Fibre Toxicology
                BioMed Central
                1743-8977
                2010
                3 September 2010
                : 7
                : 23
                Affiliations
                [1 ]Div. Surface and Corrosion Science, Royal Institute of Technology (KTH), Drottning Kristinas väg 51, SE-100 44 Stockholm, Sweden
                [2 ]Unit for Analytical Toxicology, Department of Biosciences and Nutrition, Novum, Karolinska Insitutet, SE-141 86 Huddinge, Stockholm, Sweden
                Article
                1743-8977-7-23
                10.1186/1743-8977-7-23
                2941740
                20815895
                ce533aaf-ad33-496f-8c33-810a601b2800
                Copyright ©2010 Hedberg et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 May 2010
                : 3 September 2010
                Categories
                Research

                Toxicology
                Toxicology

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