title: Comparative hazard identification by a single dose lung exposure of zinc oxide and silver nanomaterials in mice.
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.
authors.affiliation: Centre for Sustainability, Environment and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Ilse
authors.initials: I
authors.lastname: Gosens
authors.affiliation: Heriot-Watt University, School of Life Sciences, Nanosafety Research Group, Edinburgh, United Kingdom.
authors.forename: Ali
authors.initials: A
authors.lastname: Kermanizadeh
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark.
authors.forename: Nicklas Raun
authors.initials: NR
authors.lastname: Jacobsen
authors.affiliation: German Research Center for Environmental Health (GmbH), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Anke-Gabriele
authors.initials: AG
authors.lastname: Lenz
authors.affiliation: Centre for Safety of Substances and Products, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Bokkers
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Wim H
authors.initials: WH
authors.lastname: de Jong
authors.affiliation: Philips Innovation Services, Eindhoven, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Krystek
authors.affiliation: IOM, Edinburgh, United Kingdom.
authors.forename: Lang
authors.initials: L
authors.lastname: Tran
authors.affiliation: Heriot-Watt University, School of Life Sciences, Nanosafety Research Group, Edinburgh, United Kingdom.
authors.forename: Vicki
authors.initials: V
authors.lastname: Stone
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark; Department of Public Health, Copenhagen University, Copenhagen, Denmark.
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.affiliation: German Research Center for Environmental Health (GmbH), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Stoeger
authors.affiliation: Centre for Sustainability, Environment and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Institute for Risk Assessment Studies, Utrecht University, Utrecht, The Netherlands.
authors.forename: Flemming R
authors.initials: FR
authors.lastname: Cassee
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D007278:Injections, Spinal; D007322:Instillation, Drug; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D012834:Silver / Q000008:administration & dosage* / Q000633:toxicity; D018675:Toxicity Tests / Q000379:methods; D015034:Zinc Oxide / Q000008:administration & dosage* / Q000633:toxicity
chemical_list: D012834:Silver; D015034:Zinc Oxide