In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility

Our plain-English summary of In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility, by T.J. Brunner, P. Wick, P. Manser, et al (Environmental Science & Technology, 2006).

The study

• Authors: T.J. Brunner, P. Wick, P. Manser, P. Spohn, R.N. Grass, L.K. Limbach, A. Bruinink, W.J. Stark
• Journal: Environmental Science & Technology
• Published: 2006;40(14):4374-81
• Cited by: 713 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Early indicators for nanoparticle-derived adverse health effects should provide a relative measure for cytotoxicity of nanomaterials in comparison to existing toxicological data. We have therefore evaluated a human mesothelioma and a rodent fibroblast cell line for in vitro cytotoxicity tests using seven industrially important nanoparticles. Their response in terms of metabolic activity and cell proliferation of cultures exposed to 0-30 ppm nanoparticles (microg g(-1)) was compared to the effects of nontoxic amorphous silica and toxic crocidolite asbestos. Solubility was found to strongly influence the cytotoxic response. The results further revealed a nanoparticle-specific cytotoxic mechanism for uncoated iron oxide and partial detoxification or recovery after treatment with zirconia, ceria, or titania. While in vitro experiments may never replace in vivo studies, the relatively simple cytotoxic tests provide a readily available pre-screening method.

In plain English

This laboratory study tested how oxide nanoparticles affected cultured cells, using crocidolite asbestos as a toxic comparison and amorphous silica as a nontoxic one. The authors used human mesothelioma cells (MSTO-211H) and rodent fibroblast cells (3T3). Cells were exposed for 3 days (up to 30 ppm) or 6 days (up to 15 ppm) to zinc oxide, uncoated iron oxide, tricalcium phosphate, ceria, titania or zirconia. In mesothelioma cells, crocidolite had a significant toxic effect at 3.75 ppm after 6 days and at 7.5 ppm after 3 days. Silica showed no significant effects at up to 15 ppm for 6 days or up to 30 ppm for 3 days. Zinc oxide killed virtually all cells above 15 ppm. Iron oxide drastically reduced mesothelioma cells at 3.75 ppm but only slightly affected fibroblasts. Ceria, titania and zirconia had effects at 3 days but recovery by 6 days, whereas fibroblast cultures exposed to zinc or asbestos were irreversibly affected. The authors concluded that particle solubility was a useful way to group the materials. They noted that cell results have very limited validity for living organisms but may aid early screening.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: In vitro (cell culture) cytotoxicity study measuring cell activity (MTT test) and DNA content
• Who was studied: Two cell lines: human mesothelioma MSTO-211H cells and rodent 3T3 fibroblast cells. No people or animals were studied.
• Exposure: Nanoparticles of zinc oxide, uncoated iron oxide, tricalcium phosphate, ceria, titania and zirconia were compared with crocidolite asbestos (supplied by the National Research Institute for Occupational Diseases, Johannesburg) and amorphous silica. Concentrations were 0, 3.75, 7.5 and 15 ppm (micrograms per millilitre) for 6 days, or 0, 7.5, 15 and 30 ppm for 3 days.
• Main results:
  • Crocidolite asbestos (MSTO mesothelioma cells): significant toxic effect at 3.75 ppm after 6 days or at 7.5 ppm after 3 days
  • Silica: no significant effects at up to 15 ppm for 6 days or at 30 ppm for 3 days
  • Zinc oxide: virtually all MSTO or 3T3 cells died at concentrations above 15 ppm
  • Uncoated iron oxide: 3T3 fibroblasts were only slightly affected at up to 30 ppm, while activity and DNA content of MSTO mesothelioma cells were drastically reduced at as little as 3.75 ppm
  • Tricalcium phosphate: both cell cultures appeared able to deal with it across 0 to 30 ppm
  • Ceria and zirconia: cell activity and DNA content were significantly reduced at 3 days, but cells were not completely killed even at 30 ppm
  • Insoluble materials (ceria, titania, zirconia): a clear effect after short exposure, followed by recovery after 6 days
  • 3T3 fibroblasts: after 6 days the zirconia-exposed cultures recovered, while cultures exposed to zinc and asbestos were irreversibly affected
  • MSTO cells after 6 days at 7.5 ppm crocidolite: all cells became nearly spherical, grew larger, and lost adhesion to the plate
  • Rough ranking for MSTO cells after 3 days, consistent at 6 days: iron oxide about equal to asbestos, then zinc oxide, then ceria, zirconia, titania and tricalcium phosphate roughly equal
  • Iron oxide: the iron concentration that would result from complete dissolution was about 40 times lower than the known chemical toxicity of iron ions, which the authors took as evidence of an additional nanoparticle-specific effect
• The authors' conclusion: The authors concluded that particle solubility was a suitable guiding parameter for grouping the materials by their mainly chemical or physical effects.
• Limitations the authors state:
  • The authors stated that in vitro results have very limited validity for in vivo situations, though such tests may serve as an early screening system
  • The authors stated that such simple tests are not sufficient to explain the molecular mechanisms behind the observed effects
  • The authors stated that the mechanism of the recovery seen with insoluble nanoparticles needs more detailed investigation

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Fibroblast, Crocidolite.

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