Comparative hazard identification by a single dose lung exposure of zinc oxide and silver nanomaterials in mice

PLoS One. 2015 May 12;10(5):e0126934. doi: 10.1371/journal.pone.0126934. eCollection 2015.

Abstract

Comparative hazard identification of nanomaterials (NMs) can aid in the prioritisation for further toxicity testing. Here, we assessed the acute lung, systemic and liver responses in C57BL/6N mice for three NMs to provide a hazard ranking. A silver (Ag), non-functionalised zinc oxide (ZnO) and a triethoxycaprylylsilane functionalised ZnO NM suspended in water with 2% mouse serum were examined 24 hours following a single intratracheal instillation (I.T.). An acute pulmonary inflammation was noted (marked by a polymorphonuclear neutrophil influx) with cell damage (LDH and total protein) in broncho-alveolar lavage fluid (BALF) after administration of both non-functionalised and functionalised ZnO. The latter also induced systemic inflammation measured as an increase in blood neutrophils and a decrease in blood lymphocytes. Exposure to Ag NM was not accompanied by pulmonary inflammation or cytotoxicity, or by systemic inflammation. A decrease in glutathione levels was demonstrated in the liver following exposure to high doses of all three nanomaterials irrespective of any noticeable inflammatory or cytotoxic effects in the lung. By applying benchmark dose (BMD) modeling statistics to compare potencies of the NMs, we rank functionalised ZnO ranked the highest based on the largest number of affected endpoints, as well as the strongest responses observed after 24 hours. The non-functionalised ZnO NM gave an almost similar response, whereas Ag NM did not cause an acute response at similar doses.

Publication types

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

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Injections, Spinal
  • Instillation, Drug
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Nanostructures / administration & dosage
  • Nanostructures / chemistry*
  • Nanostructures / toxicity
  • Silver / administration & dosage*
  • Silver / toxicity
  • Toxicity Tests / methods
  • Zinc Oxide / administration & dosage*
  • Zinc Oxide / toxicity

Substances

  • Silver
  • Zinc Oxide

Grants and funding

This work was supported by the ENPRA project, grant agreement number 228789, funded by the EC Seventh Framework Programme theme FP7-NMP-2008-1.3-2 (http://cordis.europa.eu/fp7/home_en.html) and the grant “Danish Centre for Nanosafety” (20110092173/3) from the Danish Working Environment Research Fund (http://www.arbejdsmiljoforskning.dk/en/projekter/dansk-center-for-nanosikkerhed). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Co-author Petra Krystek is employed by Philips Innovation Services and co-author Lang Tran is employed by IOM. Philips Innovation Services and IOM provided support in the form of salaries for authors Petra Krystek and Lang Tran, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.