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Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories

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Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories. / Jacobsen, Nicklas Raun; Stoeger, Tobias; van den Brule, Sybille et al.
In: Food and chemical toxicology, Vol. 85, 11.2015, p. 84-95.

Research output: Contribution to journal › Article › peer-review

HarvardHarvard

Jacobsen, NR, Stoeger, T, van den Brule, S, Saber, AT, Beyerle, A, Vietti, G, Mortensen, A, Szarek, J, Budtz, HC, Kermanizadeh, A, Banerjee, A, Ercal, N, Vogel, U, Wallin, H & Møller, P 2015, 'Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories', Food and chemical toxicology, vol. 85, pp. 84-95. https://doi.org/10.1016/j.fct.2015.08.008

APA

Jacobsen, N. R., Stoeger, T., van den Brule, S., Saber, A. T., Beyerle, A., Vietti, G., Mortensen, A., Szarek, J., Budtz, H. C., Kermanizadeh, A., Banerjee, A., Ercal, N., Vogel, U., Wallin, H., & Møller, P. (2015). Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories. Food and chemical toxicology, 85, 84-95. https://doi.org/10.1016/j.fct.2015.08.008

CBE

Jacobsen NR, Stoeger T, van den Brule S, Saber AT, Beyerle A, Vietti G, Mortensen A, Szarek J, Budtz HC, Kermanizadeh A, et al. 2015. Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories. Food and chemical toxicology. 85:84-95. https://doi.org/10.1016/j.fct.2015.08.008

MLA

Jacobsen, Nicklas Raun et al. "Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories". Food and chemical toxicology. 2015, 85. 84-95. https://doi.org/10.1016/j.fct.2015.08.008

VancouverVancouver

Jacobsen NR, Stoeger T, van den Brule S, Saber AT, Beyerle A, Vietti G et al. Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories. Food and chemical toxicology. 2015 Nov;85:84-95. Epub 2015 Aug 7. doi: 10.1016/j.fct.2015.08.008

Author

Jacobsen, Nicklas Raun ; Stoeger, Tobias ; van den Brule, Sybille et al. / Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories. In: Food and chemical toxicology. 2015 ; Vol. 85. pp. 84-95.

RIS

TY - JOUR

T1 - Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories

AU - Jacobsen, Nicklas Raun

AU - Stoeger, Tobias

AU - van den Brule, Sybille

AU - Saber, Anne Thoustrup

AU - Beyerle, Andrea

AU - Vietti, Giulia

AU - Mortensen, Alicja

AU - Szarek, Józef

AU - Budtz, Hans Christian

AU - Kermanizadeh, Ali

AU - Banerjee, Atrayee

AU - Ercal, Nuran

AU - Vogel, Ulla

AU - Wallin, Håkan

AU - Møller, Peter

N1 - Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2015/11

Y1 - 2015/11

N2 - Inhalation is the main pathway of ZnO exposure in the occupational environment but only few studies have addressed toxic effects after pulmonary exposure to ZnO nanoparticles (NP). Here we present results from three studies of pulmonary exposure and toxicity of ZnO NP in mice. The studies were prematurely terminated because interim results unexpectedly showed severe pulmonary toxicity. High bolus doses of ZnO NP (25 up to 100 μg; ≥1.4 mg/kg) were clearly associated with a dose dependent mortality in the mice. Lower doses (≥6 μg; ≥0.3 mg/kg) elicited acute toxicity in terms of reduced weight gain, desquamation of epithelial cells with concomitantly increased barrier permeability of the alveolar/blood as well as DNA damage. Oxidative stress was shown via a strong increase in lipid peroxidation and reduced glutathione in the pulmonary tissue. Two months post-exposure revealed no obvious toxicity for 12.5 and 25 μg on a range of parameters. However, mice that survived a high dose (50 μg; 2.7 mg/kg) had an increased pulmonary collagen accumulation (fibrosis) at a similar level as a high bolus dose of crystalline silica. The recovery from these toxicological effects appeared dose-dependent. The results indicate that alveolar deposition of ZnO NP may cause significant adverse health effects.

AB - Inhalation is the main pathway of ZnO exposure in the occupational environment but only few studies have addressed toxic effects after pulmonary exposure to ZnO nanoparticles (NP). Here we present results from three studies of pulmonary exposure and toxicity of ZnO NP in mice. The studies were prematurely terminated because interim results unexpectedly showed severe pulmonary toxicity. High bolus doses of ZnO NP (25 up to 100 μg; ≥1.4 mg/kg) were clearly associated with a dose dependent mortality in the mice. Lower doses (≥6 μg; ≥0.3 mg/kg) elicited acute toxicity in terms of reduced weight gain, desquamation of epithelial cells with concomitantly increased barrier permeability of the alveolar/blood as well as DNA damage. Oxidative stress was shown via a strong increase in lipid peroxidation and reduced glutathione in the pulmonary tissue. Two months post-exposure revealed no obvious toxicity for 12.5 and 25 μg on a range of parameters. However, mice that survived a high dose (50 μg; 2.7 mg/kg) had an increased pulmonary collagen accumulation (fibrosis) at a similar level as a high bolus dose of crystalline silica. The recovery from these toxicological effects appeared dose-dependent. The results indicate that alveolar deposition of ZnO NP may cause significant adverse health effects.

KW - Animals

KW - Biomarkers/blood

KW - Crosses, Genetic

KW - DNA Damage

KW - Dose-Response Relationship, Drug

KW - Female

KW - Inhalation Exposure/adverse effects

KW - Lipid Peroxidation/drug effects

KW - Liver/drug effects

KW - Lung/drug effects

KW - Mice, Inbred C57BL

KW - Nanoparticles/administration & dosage

KW - Oxidative Stress/drug effects

KW - Particle Size

KW - Pilot Projects

KW - Pulmonary Fibrosis/chemically induced

KW - Random Allocation

KW - Respiratory Mucosa/drug effects

KW - Specific Pathogen-Free Organisms

KW - Survival Analysis

KW - Toxicity Tests, Acute

KW - Toxicity Tests, Subacute

KW - Weight Gain/drug effects

KW - Zinc Oxide/administration & dosage

U2 - 10.1016/j.fct.2015.08.008

DO - 10.1016/j.fct.2015.08.008

M3 - Article

C2 - 26260750

VL - 85

SP - 84

EP - 95

JO - Food and chemical toxicology

JF - Food and chemical toxicology

SN - 0278-6915

ER -