Biodistribution and toxicity of spherical aluminum oxide nanoparticles

J Appl Toxicol. 2016 Mar;36(3):424-33. doi: 10.1002/jat.3233. Epub 2015 Oct 5.


With the rapid development of the nano-industry, concerns about their potential adverse health effects have been raised. Thus, ranking accurately their toxicity and prioritizing for in vivo testing through in vitro toxicity test is needed. In this study, we used three types of synthesized aluminum oxide nanoparticles (AlONPs): γ-aluminum oxide hydroxide nanoparticles (γ-AlOHNPs), γ- and α-AlONPs. All three AlONPs were spherical, and the surface area was the greatest for γ-AlONPs, followed by the α-AlONPs and γ-AlOHNPs. In mice, γ-AlOHNPs accumulated the most 24 h after a single oral dose. Additionally, the decreased number of white blood cells (WBC), the increased ratio of neutrophils and the enhanced secretion of interleukin (IL)-8 were observed in the blood of mice dosed with γ-AlOHNPs (10 mg kg(-1)). We also compared their toxicity using four different in vitro test methods using six cell lines, which were derived from their potential target organs, BEAS-2B (lung), Chang (liver), HACAT (skin), H9C2 (heart), T98G (brain) and HEK-293 (kidney). The results showed γ-AlOHNPs induced the greatest toxicity. Moreover, separation of particles was observed in a transmission electron microscope (TEM) image of cells treated with γ-AlOHNPs, but not γ-AlONPs or α-AlONPs. In conclusion, our results suggest that the accumulation and toxicity of AlONPs are stronger in γ-AlOHNPs compared with γ-AlONPs and α-AlONPs owing their low stability within biological system, and the presence of hydroxyl group may be an important factor in determining the distribution and toxicity of spherical AlONPs.

Keywords: aluminum oxide hydroxide nanoparticles; aluminum oxide nanoparticles; distribution; toxicity; toxicity screening.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Administration, Oral
  • Aluminum Hydroxide / metabolism
  • Aluminum Hydroxide / toxicity*
  • Aluminum Oxide / metabolism
  • Aluminum Oxide / toxicity*
  • Animals
  • Biological Assay
  • Biomarkers / blood
  • Brain / drug effects
  • Brain / metabolism
  • Brain / ultrastructure
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Humans
  • Interleukin-8 / blood
  • Kidney / drug effects
  • Kidney / ultrastructure
  • L-Lactate Dehydrogenase / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / ultrastructure
  • Lung / drug effects
  • Lung / metabolism
  • Lung / ultrastructure
  • Male
  • Metal Nanoparticles / toxicity*
  • Mice, Inbred ICR
  • Microscopy, Electron, Transmission
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / ultrastructure
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Particle Size
  • Rats
  • Risk Assessment
  • Skin / drug effects
  • Skin / metabolism
  • Skin / ultrastructure
  • Surface Properties
  • Time Factors
  • Tissue Distribution


  • Biomarkers
  • Interleukin-8
  • Aluminum Hydroxide
  • aluminum oxide hydroxide
  • Adenosine Triphosphate
  • L-Lactate Dehydrogenase
  • Aluminum Oxide