Decreased dissolution of ZnO by iron doping yields nanoparticles with reduced toxicity in the rodent lung and zebrafish embryos

Details

• Personal Author:
  Castranova, Vincent ; George S ; Ji Z ; Li N ; Lin S ; Madler L ; Meng H ; Nel AE ; Pokhrel S ; Sager T ; Schoenfeld D ; Wang M ; Wang X ; Xia, T. ; Zhao Y ; Zink JI
• Description:
  We have recently shown that the dissolution of ZnO nanoparticles and Zn2þ shedding leads to a series of sublethal and lethal toxicological responses at the cellular level that can be alleviated by iron doping. Iron doping changes the particle matrix and slows the rate of particle dissolution. To determine whether iron doping of ZnO also leads to lesser toxic effects in vivo, toxicity studies were performed in rodent and zebrafish models. First, we synthesized a fresh batch of ZnO nanoparticles doped with 1-10 wt % of Fe. These particles were extensively characterized to confirm their doping status, reduced rate of dissolution in an exposure medium, and reduced toxicity in a cellular screen. Subsequent studies compared the effects of undoped to doped particles in the rat lung, mouse lung, and the zebrafish embryo. The zebrafish studies looked at embryo hatching and mortality rates as well as the generation of morphological defects, while the endpoints in the rodent lung included an assessment of inflammatory cell infiltrates, LDH release, and cytokine levels in the bronchoalveolar lavage fluid. Iron doping, similar to the effect of the metal chelator, DTPA, interfered in the inhibitory effects of Zn2þ on zebrafish hatching. In the oropharyngeal aspiration model in the mouse, iron doping was associated with decreased polymorphonuclear cell counts and IL-6 mRNA production. Doped particles also elicited decreased heme oxygenase 1 expression in the murine lung. In the intratracheal instillation studies in the rat, Fe doping was associated with decreased polymorphonuclear cell counts, LDH, and albumin levels. All considered, the above data show that Fe doping is a possible safe design strategy for preventing ZnO toxicity in animals and the environment. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Cytotoxins Hazardous Substances Irritants Laboratories Lung Occupational Health Particulate Matter Respiratory System Safety Toxicology

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• Keywords:
  Author Keywords: ZnO Cell-biology Cell-cultures Cellular-reactions Cellular-uptake Cytotoxic-effects Dissolution Embryo In-vitro-studies Injury-prevention Iron Doping Laboratory-testing Lung-cells Lung-function Lung-irritants Lung-tissue Molecular-structure Mouse Nanotechnology Particulate-sampling-methods Particulates Pulmonary-system Pulmonary Toxicity Rat Respiratory-irritants Toxic-effects Toxins Zebrafish

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• ISSN:
  1936-0851
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  5
• Issue:
  2
• NIOSHTIC Number:
  nn:20038504
• Citation:
  ACS Nano 2011 Jan; 5(2):1223-1235
• Contact Point Address:
  Andre E. Nel, Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, California 90095, USA
• Email:
  anel@mednet.ucla.edu
• CAS Registry Number:
  Iron (CAS RN 7439-89-6)
• Federal Fiscal Year:
  2011
• Peer Reviewed:
  True
• Source Full Name:
  ACS Nano
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fe02381fcfeafc7a4b449438b634b975fec51170385aa24b33ccdab0f0b942ccb34db5d14e3b46df1cb520d776048a2e0aa974c6c47dbb56e3c08b4923ca18ea
• Download URL:
  https://stacks.cdc.gov/view/cdc/192192/cdc_192192_DS1.pdf
• File Type:
  [PDF - 4.03 MB ]