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An in vitro alveolar macrophage assay for predicting the short-term inhalation toxicity of nanomaterials
Open accessAbstract
BACKGROUND: Most in vitro studies investigating nanomaterial pulmonary toxicity poorly correlate to in vivo inhalation studies. Alveolar macrophages (AMs) play an outstanding role during inhalation exposure since they effectively clear the alveoli from particles. This study addresses the applicability of an in vitro alveolar macrophage assay to distinguish biologically active from passive nanomaterials. METHODS: Rat NR8383 alveolar macrophages were exposed to 18 inorganic nanomaterials, covering AlOOH, BaSO4, CeO2, Fe2O3, TiO2, ZrO2, and ZnO NMs, amorphous SiO2 and graphite nanoplatelets, and two nanosized organic pigments. ZrO2 and amorphous SiO2 were tested without and with surface functionalization. Non-nanosized quartz DQ12 and corundum were used as positive and negative controls, respectively. The test materials were incubated with the cells in protein-free culture medium. Lactate dehydrogenase, glucuronidase, and tumour necrosis factor alpha were assessed after 16 h. In parallel, H2O2 was assessed after 1.5 h. Using the no-observed-adverse-effect concentrations (NOAECs) from available rat short-term inhalation studies (STIS), the test materials were categorized as active (NOAEC < 10 mg/m(3)) or passive. RESULTS: In vitro data reflected the STIS categorization if a particle surface area-based threshold of <6000 mm(2)/mL was used to determine the biological relevance of the lowest observed significant in vitro effects. Significant effects that were recorded above this threshold were assessed as resulting from test material-unspecific cellular 'overload'. Test materials were assessed as active if ≥2 of the 4 in vitro parameters undercut this threshold. They were assessed as passive if 0 or 1 parameter was altered. An overall assay accuracy of 95 % was achieved. CONCLUSIONS: The in vitro NR8383 alveolar macrophage assay allows distinguishing active from passive nanomaterials. Thereby, it allows determining whether in vivo short-term inhalation testing is necessary for hazard assessment. Results may also be used to group nanomaterials by biological activity. Further work should aim at validating the assay.
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“At this stage, the internalized portion of the fibre measured ca. 26 μm, which is roughly twice the size of a typical NR8383 macrophage in its detached and rounded state (12.5 –12.8 μm) [28].”
From Macrophages bend long fibres with flexural rigidity lower than 3 mN·nm2 to avoid frustrated phagocytosis (2026) · cites this paper as [28]
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“On average, human alveolar macrophages are larger than rat alveolar macrophages, with mean diameters of approximately 21.2 ± 0.3 μm and 13.1 ± 2.5 μm, respectively [28, 45].”
From Macrophages bend long fibres with flexural rigidity lower than 3 mN·nm2 to avoid frustrated phagocytosis (2026) · cites this paper as [28]
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“The biological responses of NR8383 cells to nanomaterials are well documented and have been shown to correlate with in vivo outcomes [28]. This supports their use as a predictive model and contributes to the reduction and refinement of animal experiments.”
From Macrophages bend long fibres with flexural rigidity lower than 3 mN·nm2 to avoid frustrated phagocytosis (2026) · cites this paper as [28]
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Metadata
- Authors
- Wiemann, M., Vennemann, A., Sauer, U. G., Wiench, K., Ma-Hock, L., & Landsiedel, R.
- Affiliations
- BASF (Germany) (DE)
- Corresponding author
- Wiemann, Martin
- Venue
- Journal of Nanobiotechnology
- Published
- 2016-03-05
- Volume
- 14
- Issue
- 1
- Pages
- 16-16
- ISSN
- 1477-3155 (ISSN-L)
- PMC
- PMC4779246
- OpenAlex
- W2290248210
- Cited by
- 152
- References
- 120
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 12 · 2023: 12 · 2022: 18 · 2021: 14 · 2020: 18 · 2019: 18 · 2018: 17 · 2017: 18 · 2016: 6
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Nanobiotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (03X0105, 0315483A)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- alveolar macrophages, NR8383 cells, in vitro-in vivo correlation, zirconia nanoparticles, amorphous silica nanoparticles, surface functionalization, hazard assessment, cytotoxicity, oxidative stress
- MeSH terms
- Animals, Cell Line, Ferric Compounds, Graphite, Hydrogen Peroxide, Lung, Particle Size, Silicon Dioxide, Titanium, Macrophages, Alveolar, Inhalation Exposure, Nanostructures, Rats
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