A 13-week repeated-dose oral toxicity and bioaccumulation of aluminum oxide nanoparticles in mice

Arch Toxicol. 2015 Mar;89(3):371-9. doi: 10.1007/s00204-014-1256-0. Epub 2014 May 6.


Because of an increase in the commercial applications of manufactured nanoparticles, the issue of potential adverse health effects of nanoparticles following intended or unintended exposure is rapidly gaining attention. In this study, we evaluated the toxicity of aluminum oxide nanoparticles (AlNPs, rod-type, 1.5, 3, and 6 mg/kg) after oral administration to mice for 13 weeks. Compared with the control group, the consumption of diet and drinking water and body weight gain decreased in the group treated with AlNPs. The group treated with 6 mg/kg AlNPs also showed a marked elevation in the count of white blood cells that associated with a significant decrease and increase to the proportion of eosinophils and lymphocytes, respectively. In addition, the secretion of IL-6 and monocyte chemotactic protein-1 increased in a dose-dependent manner in the treated groups. Furthermore, AlNPs showed the highest accumulation in the liver and kidneys compared with the control group, increased the lactate dehydrogenase level in the blood, and induced the development of a pathological lesion in the liver and kidneys. Taken together, we suggest that the target organs of rod-type AlNPs may be the liver, kidneys and the immune system, and the not-observed adverse effect level may be lower than 6 mg/kg.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aluminum Oxide / chemistry
  • Aluminum Oxide / pharmacokinetics
  • Aluminum Oxide / toxicity*
  • Animals
  • Dose-Response Relationship, Drug
  • Immune System / drug effects*
  • Immune System / metabolism
  • Immune System / pathology
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice, Inbred ICR
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity*
  • Organ Specificity
  • Toxicity Tests, Subchronic* / methods


  • Aluminum Oxide