Evidence map›Paper›PMID 25424549›Full record

ArticleJournal of nanobiotechnology2014

Comparative lung toxicity of engineered nanomaterials utilizing in vitro, ex vivo and in vivo approaches.

Yong Ho Kim, Elizabeth Boykin, Tina Stevens, Katelyn Lavrich, M Ian Gilmour

Registry-linked trialAbstract readComparative Study
In one paragraph

Article in Journal of nanobiotechnology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07506850 (Efficacy of Casein Phosphopeptide-Amorphous Calcium Phosphate Associated With Sodium Fluoride or Stannous Fluoride in Reducing Tooth Sensitivity After In-office Dental Bleaching), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing 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.

NCT07506850 nacompletednot on this mapstarted 2025, after this paper: background citation

Efficacy of Casein Phosphopeptide-Amorphous Calcium Phosphate Associated With Sodium Fluoride or Stannous Fluoride in Reducing Tooth Sensitivity After In-office Dental Bleaching: a Randomized Clinical Trial.

TypeinterventionalSponsorUniversidade Federal do ParaRan2025 to 2026Enrolled64ConditionsTooth SensitivityArmsCPP-ACPF, CPP-ACP+SnF2, Control (placebo)
3 · Its place in the literature

Who cites it

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

  1. Adverse effects and underlying mechanism of rare earth elements.Environmental health : a global access science source · 2025
    Pooled it
  2. Review
  3. Article
  4. Review
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  6. Article
  7. Approach towardEnvironmental science & technology · 2022
    Article
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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

5 authors.

Yong Ho KimCurriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. kim.yongho@epa.gov.
Elizabeth BoykinEnvironmental Public Health Division, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC, USA. boykin.elizabeth@epa.gov.
Tina StevensResearch Triangle Park Division, National Center for Environmental Assessment, United States Environmental Protection Agency, Research Triangle Park, NC, USA. stevens.tina@epa.gov.
Katelyn LavrichCurriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Lavrich.klavrich@email.unc.edu.
M Ian GilmourEnvironmental Public Health Division, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC, USA. gilmour.ian@epa.gov.

Funding

TOXICOLOGYT32ES007126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ILONA JASPERS, Bernard E. Weissman · 1985 to 2026
$13.0M
NIEHS NIH HHS T32 ES007126
6 · The paper itself

Abstract

backgroundAlthough engineered nanomaterials (ENM) are currently regulated either in the context of a new chemical, or as a new use of an existing chemical, hazard assessment is still to a large extent reliant on information from historical toxicity studies of the parent compound, and may not take into account special properties related to the small size and high surface area of ENM. While it is important to properly screen and predict the potential toxicity of ENM, there is also concern that current toxicity tests will require even heavier use of experimental animals, and reliable alternatives should be developed and validated. Here we assessed the comparative respiratory toxicity of ENM in three different methods which employed in vivo, in vitro and ex vivo toxicity testing approaches.

methodsToxicity of five ENM (SiO2 (10), CeO2 (23), CeO2 (88), TiO2 (10), and TiO2 (200); parentheses indicate average ENM diameter in nm) were tested in this study. CD-1 mice were exposed to the ENM by oropharyngeal aspiration at a dose of 100 μg. Mouse lung tissue slices and alveolar macrophages were also exposed to the ENM at concentrations of 22-132 and 3.1-100 μg/mL, respectively. Biomarkers of lung injury and inflammation were assessed at 4 and/or 24 hr post-exposure.

resultsSmall-sized ENM (SiO2 (10), CeO2 (23), but not TiO2 (10)) significantly elicited pro-inflammatory responses in mice (in vivo), suggesting that the observed toxicity in the lungs was dependent on size and chemical composition. Similarly, SiO2 (10) and/or CeO2 (23) were also more toxic in the lung tissue slices (ex vivo) and alveolar macrophages (in vitro) compared to other ENM. A similar pattern of inflammatory response (e.g., interleukin-6) was observed in both ex vivo and in vitro when a dose metric based on cell surface area (μg/cm(2)), but not culture medium volume (μg/mL) was employed.

conclusionExposure to ENM induced acute lung inflammatory effects in a size- and chemical composition-dependent manner. The cell culture and lung slice techniques provided similar profiles of effect and help bridge the gap in our understanding of in vivo, ex vivo, and in vitro toxicity outcomes.

Indexed as

AnimalsCells, CulturedCeriumCytokinesFemaleIn Vitro TechniquesLungMacrophages, AlveolarMice, Inbred StrainsNanostructuresParticle SizePneumoniaSilicon DioxideTitaniumToxicity Testsceric oxideCeriumCytokinesSilicon DioxideTitaniumtitanium dioxide

Identifiers

PMID25424549
PMCPMC4262188

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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.