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

Nicklas Raun Jacobsen; Tobias Stoeger; Sybille van den Brule; Anne Thoustrup Saber; Andrea Beyerle; Giulia Vietti; Alicja Mortensen; Józef Szarek; Hans Christian Budtz; Ali Kermanizadeh; Atrayee Banerjee; Nuran Ercal; Ulla Vogel; Erik Håkan Richard Wallin; Peter Møller

doi:10.1016/j.fct.2015.08.008

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

Nicklas Raun Jacobsen, Tobias Stoeger, Sybille van den Brule, Anne Thoustrup Saber, Andrea Beyerle, Giulia Vietti, Alicja Mortensen, Józef Szarek, Hans Christian Budtz, Ali Kermanizadeh, Atrayee Banerjee, Nuran Ercal, Ulla Vogel, Erik Håkan Richard Wallin, Peter Møller

54 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
Volume	85
Pages (from-to)	84-95
Number of pages	12
ISSN	0278-6915
DOIs	https://doi.org/10.1016/j.fct.2015.08.008
Publication status	Published - 1 Nov 2015

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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, E. H. R., & 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 : an international journal published for the British Industrial Biological Research Association, 85, 84-95. https://doi.org/10.1016/j.fct.2015.08.008

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 : an international journal published for the British Industrial Biological Research Association, Vol. 85, 01.11.2015, p. 84-95.

Research output: Contribution to journal › Journal article › Research › peer-review

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, EHR & 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 : an international journal published for the British Industrial Biological Research Association, vol. 85, pp. 84-95. https://doi.org/10.1016/j.fct.2015.08.008

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 : an international journal published for the British Industrial Biological Research Association. 2015 Nov 1;85:84-95. doi: 10.1016/j.fct.2015.08.008

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

abstract = "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.",

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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, Erik Håkan Richard

AU - Møller, Peter

PY - 2015/11/1

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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.

U2 - 10.1016/j.fct.2015.08.008

DO - 10.1016/j.fct.2015.08.008

M3 - Journal article

C2 - 26260750

SN - 0278-6915

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SP - 84

EP - 95

JO - Food and Chemical Toxicology

JF - Food and Chemical Toxicology

ER -

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

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