Efficacy of Simple Short-Term in Vitro Assays for Predicting the Potential of Metal Oxide Nanoparticles to Cause Pulmonary Inflammation

University of Edinburgh, Edinburgh, UK.
Environmental Health Perspectives (Impact Factor: 7.98). 03/2009; 117(2):241-7. DOI: 10.1289/ehp.11811
Source: PubMed


There has been concern regarding risks from inhalation exposure to nanoparticles (NPs). The large number of particles requiring testing means that alternative approaches to animal testing are needed.
We set out to determine whether short-term in vitro assays that assess intrinsic oxidative stress potential and membrane-damaging potency of a panel of metal oxide NPs can be used to predict their inflammogenic potency.
For a panel of metal oxide NPs, we investigated intrinsic free radical generation, oxidative activity in an extracellular environment, cytotoxicity to lung epithelial cells, hemolysis, and inflammation potency in rat lungs. All exposures were carried out at equal surface area doses.
Only nickel oxide (NiO) and alumina 2 caused significant lung inflammation when instilled into rat lungs at equal surface area, suggesting that these two had extra surface reactivity. We observed significant free radical generation with 4 of 13 metal oxides, only one of which was inflammogenic. Only 3 of 13 were significantly hemolytic, two of which were inflammogenic.
Potency in generating free radicals in vitro did not predict inflammation, whereas alumina 2 had no free radical activity but was inflammogenic. The hemolysis assay was correct in predicting the proinflammatory potential of 12 of 13 of the particles examined. Using a battery of simple in vitro tests, it is possible to predict the inflammogenicity of metal oxide NPs, although some false-positive results are likely. More research using a larger panel is needed to confirm the efficacy and generality of this approach for metal oxide NPs.

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    • "In the context of this paper, the term ''catalytic'' is used in the sense of a classical catalyzed reaction, while ''biological'' activity circumscribes effects in biological systems. As in previous studies, ROS production was chosen as a suitable marker for biological effects, because the oxidative potential of nanoparticles is considered a good first indicator of nanotoxicity (Ayres et al., 2008; Kovacic & Somanathan, 2010; Lu et al., 2009; Nel et al., 2006; Xia et al., 2008). ROS production was measured both in a cell-free environment and in THP-1 (human monocytic leukemia) cell lines, after transferring the particles into suspension. "
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    • "Some studies have demonstrated that pathogenic mechanisms initiated by bulk metal oxide and its NPs are dominated by inflammation-driven effects, including, oxidative stress, apoptosis and DNA damage (Borm et al., 2006; Lu et al., 2009; Xiong et al., 2011). "
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