Particle Size and Biological Fate of ZnO Do Not Cause Acute Toxicity, but Affect Toxicokinetics and Gene Expression Profiles in the Rat Livers after Oral Administration

Zinc oxide (ZnO) particles have been used as dietary supplements because zinc is an essential trace element for humans. Along with the rapid development of nanotechnology, the use of ZnO nanoparticles (NPs) is increasing in the food industry, but their oral toxicity potential still remains to be answered. In this study, the effects of particle size and biological fate of ZnO on acute toxicity, toxicokinetics, and gene expression profiles in the livers were investigated after oral administration of ZnO NPs (N-ZnO), bulk-sized ZnO (B-ZnO) or Zn ions in rats. The plasma concentration-time profiles after a single-dose oral administration of ZnOs differed depending on particle/ionic forms and particle size, showing high absorption of Zn ions, followed by N-ZnO and B-ZnO, although in vivo solubility did not differ from particle size. No significant acute toxicity was found after oral administration of ZnOs for 14 days in rats. However, transcriptomic responses in the livers were differently affected, showing that metabolic process and metal biding were up-regulated by Zn ions and N-ZnO, respectively, which were not pronounced in the liver treated with B-ZnO. These findings will be useful to predict the potential oral toxicity of ZnO NPs and further mechanistic and long-term exposure studies are required to assume their safety.