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

Ilse Gosens, Ali Kermanizadeh, Nicklas Raun Jacobsen, Anke Gabriele Lenz, Bas Bokkers, Wim H. De Jong, Petra Krystek, Lang Tran, Vicki Stone, Håkan Wallin, Tobias Stoeger, Flemming R. Cassee

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    28 Citations (Scopus)

    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 (IT.). 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.

    Original languageEnglish
    Article number0126934
    JournalPLoS ONE
    Volume10
    Issue number5
    DOIs
    Publication statusPublished - 12 May 2015

    ASJC Scopus subject areas

    • Agricultural and Biological Sciences(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)

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  • Cite this

    Gosens, I., Kermanizadeh, A., Jacobsen, N. R., Lenz, A. G., Bokkers, B., De Jong, W. H., Krystek, P., Tran, L., Stone, V., Wallin, H., Stoeger, T., & Cassee, F. R. (2015). Comparative hazard identification by a single dose lung exposure of zinc oxide and silver nanomaterials in mice. PLoS ONE, 10(5), [0126934]. https://doi.org/10.1371/journal.pone.0126934