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

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

doi:10.1371/journal.pone.0126934

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.

Highlights

The potential for consumer and occupational exposure will rise with increasing production of nanomaterials (NMs)
The details on raw material characteristics, such as primary particle size as stated by the manufacturer, X-ray diffraction (XRD) size and transmission electron microscopy (TEM), surface area according to Brunauer Emmett Teller (BET) and coating have been described previously [4] and are briefly summarized in S1 Table
For both zinc oxide (ZnO) NMs, increases in the neutrophil numbers (PMN) and IL-6 levels in the broncho-alveolar lavage fluid (BALF) were noted as sensitive markers for lung inflammation

Summary

Introduction

The potential for consumer and occupational exposure will rise with increasing production of nanomaterials (NMs). We focus on the hazard identification of in vivo acute effects after 24 hours after a single intratracheal instillation (I.T.) of three selected NMs (non-functionalised ZnO, functionalised ZnO and a suspended silver NM). These NMs are available in the JRC NMs repository and are examples of commercial materials used in various applications [2, 3]. Shape, surface area, surface chemistry such as coatings and agglomeration state amongst others prior to administration of the materials have been determined [4] Within this consortium, seven additional NMs have been characterised, including five types of titanium dioxide and two types of multiwall carbon nanotubes. A commonly used healthy mouse model (C57BL6) was chosen for the entire EU project that allowed a comparison with other studies within this project using a genetically modified strain on a C57BL6 background

Methods

Results

Discussion

Conclusion