TY - JOUR

T1 - Comparative hazard identification by a single dose lung exposure of zinc oxide and silver nanomaterials in mice

AU - Gosens, Ilse

AU - Kermanizadeh, Ali

AU - Jacobsen, Nicklas Raun

AU - Lenz, Anke-Gabriele

AU - Bokkers, Bas

AU - de Jong, Wim H

AU - Krystek, Petra

AU - Tran, Lang

AU - Stone, Vicki

AU - Wallin, Håkan

AU - Stoeger, Tobias

AU - Cassee, Flemming R

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

KW - Animals

KW - Bronchoalveolar Lavage Fluid/chemistry

KW - Injections, Spinal

KW - Instillation, Drug

KW - Lung/drug effects

KW - Mice

KW - Mice, Inbred C57BL

KW - Nanostructures/administration & dosage

KW - Silver/administration & dosage

KW - Toxicity Tests/methods

KW - Zinc Oxide/administration & dosage

U2 - 10.1371/journal.pone.0126934

DO - 10.1371/journal.pone.0126934

M3 - Article

C2 - 25966284

VL - 10

SP - e0126934

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 5

ER -