Testing Metal‐Oxide Nanomaterials for Human Safety

Landsiedel, Robert; Ma‐Hock, Lan; Kröll, Alexandra; Hahn, Daniela; Schnekenburger, Jürgen; Wiench, Karin; Wohlleben, Wendel

doi:10.1002/adma.200902658

Cited by 358 publications

(257 citation statements)

References 172 publications

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“…Furthermore, a high-dosed spray was modeled based on doses and particle size distributions reported for some consumer sprays (Quadros & Marr, 2011) as well as high dose experiments on rats (Landsiedel et al, 2010. For the NPs a dose equivalent to 1 Â 10 8 particles/cm 3 of the respective NP at an agglomerated state of CMD ¼ 250 nm and a GSD ¼ 2.0 (corresponding to 2.476 mm MMAD) was assumed.…”

Section: Resultsmentioning

confidence: 99%

Comparative modeling of exposure to airborne nanoparticles released by consumer spray products

2015

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Consumer exposure to sprays containing nano-objects is a continuing concern as a potential health hazard. One potential hazard has been formulated in the overload hypothesis. It describes a volume fraction of the macrophages that is occupied by deposited nanoparticles that leads to reduced macrophage mobility. Subsequent chronic inflammation may then lead to severe health consequences including cancer. To calculate lung deposition of spherical particles, the Multiple-Path Particle Dosimetry (MPPD) model (ARA, Albuquerque, NM) provides different kinds of lung models and age settings. Using the MPPD v 2.11 software, we modeled several consumer-related exposure scenarios. Different body orientations and age groups were investigated. Moreover, a number of materials representing different densities were used, and the exposure calculated using MPPD is compared to the hazard derived from the overload hypothesis. Conditions leading to macrophage overload were found for exposures to high particle doses for prolonged times and repeated exposure. Such conditions are unlikely in the context of regular consumer exposure. The overload hypothesis assumes the particles to be inert and biopersistent, a condition that currently lacks a clear regulatory definition and is valid only for a few selected materials. Furthermore, because of material-specific effects and the possibility of surface adsorption of hazardous chemicals, nano-objects in propellant sprays remain of concern for consumer health.

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Section: Resultsmentioning

confidence: 99%

Comparative modeling of exposure to airborne nanoparticles released by consumer spray products

2015

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“…TEM results revealed that serum in the culture medium contributed substantially to particle dispersion and allowed particles to enter the human lung cells. In serum-free medium, MNPs underwent rapid aggregation apparently because of a high ionic strength of culture medium [30] and no MNPs were found inside the cells. A rapid agglomeration of polyvinyl alcohol/vinyl amine coated magnetite nanoparticles in serum-free medium have reported also Petri-Fink et al [31].…”

Section: Discussionmentioning

confidence: 99%

The intensity of internalization and cytotoxicity of superparamagnetic iron oxide nanoparticles with different surface modifications in human tumor and diploid lung cells

Mesárošová

Cĭampor²,

Závišová³

et al. 2012

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The human lung adenocarcinoma epithelial (A549) cells and the human embryo lung (HEL 12469) cells were used to investigate the uptake and cytotoxicity of magnetite nanoparticles (MNPs) with different chemically modified surfaces. MNPs uptake was an energy-dependent process substantially affected by the serum concentration in the culture medium. Internalized MNPs localized in vesicle-bound aggregates were observed in the cytoplasm, none in the nucleus or in mitochondria. All MNPs induced a dose-and time-dependent increase in cytotoxicity in both human lung cell lines. The cytotoxicity of MNPs increased proportionally with the particle size. Since the cytotoxicity of MNPs was nearly identical when the doses were equalized based on particle surface area, we suppose that the particle surface area rather than the surface modifications per se underlay the cytotoxicity of MNPs. In general, higher internalized amount of MNPs was found in HEL 12469 cells compared with A549 cells. Accordingly, the viability of the human embryo lung cells was reduced more substantially than that of the adenocarcinoma lung cells. The weak MNPs uptake into A549 cells might be of biomedical relevance in cases where MNPs should be used as nanocarriers for targeted drug delivery in tumor tissue derived from alveolar epithelial cells.

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“…This conformity suggests that serum proteins adsorbed onto the particle surface, with the result that protein-coated ZnO particles appeared electrostatically to be like the free serum proteins. Such zeta potential values of protein-covered particles in physiological media are often found and seem to be particleindependent [23,45,46].…”

Section: Discussionmentioning

confidence: 99%

Implications of the stability behavior of zinc oxide nanoparticles for toxicological studies

2014

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The increasing use of zinc oxide (ZnO) nanoparticles in sunscreens and other cosmetic products demands a risk assessment that has to be done in toxicological studies. Such investigations require profound knowledge of the behavior of ZnO in cell culture media. The current study was performed to get well-dispersed suspensions of a hydrophilic (ZnO-hydro) and a lipophilic coated (ZnO-lipo) ZnO nanomaterial for use in in vitro tests. Therefore, systematic tests were carried out with common dispersants (phosphate, lecithin, proteins) to elucidate chemical and physical changes of ZnO nanoparticles in water and physiological solutions (PBS, DMEM). Nonphysiological stock suspensions were prepared using ultrasonication. Time-dependent changes of pH, conductivity, zeta potential, particle size and dissolution were recorded. Secondly, the stock suspensions were added to physiological media with or without albumin (BSA) or serum (FBS), to examine characteristics such as agglomeration and dissolution. Stable stock suspensions were obtained using phosphate as natural and physiological electrostatic stabilizing agent. Lecithin proved to be an effective wetting agent for ZnO-lipo. Although the particle size remained constant, the suspension changed over time. The pH increased as a result of ZnO dissolution and formation of zinc phosphate complexes. The behavior of ZnO in physiological media was found to depend strongly on the additives used. Applying only phosphate as additive, ZnOhydro agglomerated within minutes. In the presence of lecithin or BSA/serum, agglomeration was inhibited. ZnO dissolution was higher under physiological conditions than in the stock suspension. Serum especially promoted this process. Using body-related dispersants (phosphate, lecithin) non-agglomerating stock suspensions of hydrophilic and lipophilic ZnO were prepared as a prerequisite to perform meaningful toxicological investigation. Both nanomaterials showed a non-negligible dissolution behavior that strongly depended on the surrounding conditions. Agglomeration of ZnO particles in physiological media is a complex function of particle coating, used dispersants and serum proteins if supplemented. The present study gives a clear guideline how to prepare and handle suspensions with ZnO for in vitro testing and allows the correlation between the chemical-physical particles behavior with findings from toxicological tests.

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Testing Metal‐Oxide Nanomaterials for Human Safety

Cited by 358 publications

References 172 publications

Comparative modeling of exposure to airborne nanoparticles released by consumer spray products

Comparative modeling of exposure to airborne nanoparticles released by consumer spray products

The intensity of internalization and cytotoxicity of superparamagnetic iron oxide nanoparticles with different surface modifications in human tumor and diploid lung cells

Implications of the stability behavior of zinc oxide nanoparticles for toxicological studies

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