Evidence map›Paper›PMID 26944705›Full record

ArticleJournal of nanobiotechnology2016

An in vitro alveolar macrophage assay for predicting the short-term inhalation toxicity of nanomaterials.

Martin Wiemann, Antje Vennemann, Ursula G Sauer, Karin Wiench, Lan Ma-Hock, Robert Landsiedel

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Readiness of theFrontiers in toxicology · 2026
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  13. Environmental science. Nano · 2024
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  20. Predicting nanomaterials pulmonary toxicity in animals by cell culture models: Achievements and perspectives.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2022
    Review

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Martin WiemannIBR R&D gGmbH Institute for Lung Health, Mendelstraße 11, 48149, Münster, Germany. martin.wiemann@ibe-ms.de.
Antje VennemannIBR R&D gGmbH Institute for Lung Health, Mendelstraße 11, 48149, Münster, Germany. vennemann@ibe-ms.de.
Ursula G SauerScientific Consultancy - Animal Welfare, Hallstattfeld 16, 85579, Neubiberg, Germany. ursula.sauer@sauerug.de.
Karin WienchBASF SE, Experimental Toxicology and Ecology, GB/TB - Z470, 67056, Ludwigshafen, Germany. karin.wiench@basf.com.
Lan Ma-HockBASF SE, Experimental Toxicology and Ecology, GB/TB - Z470, 67056, Ludwigshafen, Germany. lan.ma-hock@basf.com.
Robert LandsiedelBASF SE, Experimental Toxicology and Ecology, GB/TB - Z470, 67056, Ludwigshafen, Germany. robert.landsiedel@basf.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMost 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.

methodsRat 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.

resultsIn 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.

conclusionsThe 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.

Indexed as

AnimalsCell LineFerric CompoundsGraphiteHydrogen PeroxideInhalation ExposureLungMacrophages, AlveolarNanostructuresParticle SizeRatsSilicon DioxideTitaniumFerric CompoundsGraphiteHydrogen PeroxideSilicon DioxideTitanium

Identifiers

PMID26944705
PMCPMC4779246

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.