Time-response relationship of nano and micro particle induced lung inflammation. Quartz as reference compound

Martin Roursgaard; Steen Seier Poulsen; Lars K. Poulsen; Maria Hammer; Keld A. Jensen; Satoshi Utsunomiya; Rodney C. Ewing; Tonci Balic Zunic; Gunnar D. Nielsen; Søren T. Larsen

doi:10.1177/0960327110363329

Time-response relationship of nano and micro particle induced lung inflammation. Quartz as reference compound

Martin Roursgaard, Steen Seier Poulsen, Lars K. Poulsen, Maria Hammer, Keld A. Jensen, Satoshi Utsunomiya, Rodney C. Ewing, Tonci Balic Zunic, Gunnar D. Nielsen, Søren T. Larsen

31 Citations (Scopus)

Abstract

An increasing number of engineered particles, including nanoparticles, are being manufactured, increasing the need for simple low-dose toxicological screening methods. This study aimed to investigate the kinetics of biomarkers related to acute and sub-chronic particle-induced lung inflammation of quartz. Mice were intratracheal instilled with 50 μg of microsized or nanosized quartz. Acute inflammation was assessed 1, 2, 4, 8, 16 or 48 hours post exposure, whereas sub-chronic inflammation was investigated 3 months after exposure. Markers of acute inflammation in the bronchoalveolar lavage fluid (BALF) were neutrophils (PMN), tumor necrosis factor-alfa (TNF-α), interleukin (IL)-1β, macrophage inflammatory protein-2 (MIP-2), keratinocyte derived chemokine (KC) and total protein, which were all close to maximum 16 hours post instillation. No major differences were seen in the time-response profiles of nano- and micro-sized particles. The potency of the two samples cannot be compared; during the milling process, a substantial part of the quartz was converted to amorphous silica and contaminated with corundum. For screening, BALF PMN, either TNF-α or IL-1β at 16 hours post instillation may be useful. At 3 months post instillation, KC, PMN and macrophages were elevated. Histology showed no interstitial inflammation three months post instillation. For screening of sub-chronic effects, KC, PMN, macrophages and histopathology is considered sufficient.

Original language	English
Journal	Human & Experimental Toxicology
Volume	29
Issue number	11
Pages (from-to)	915-933
Number of pages	19
ISSN	0960-3271
DOIs	https://doi.org/10.1177/0960327110363329
Publication status	Published - Nov 2010

Keywords

Animals
Bronchoalveolar Lavage Fluid
Cytokines
Dose-Response Relationship, Drug
Female
Inhalation Exposure
Mice
Mice, Inbred BALB C
Microscopy, Electron, Transmission
Nanoparticles
Neutrophils
Particle Size
Pneumonia
Powder Diffraction
Quartz
Surface Properties
Time Factors
Toxicity Tests
X-Ray Diffraction

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https://journals.sagepub.com/doi/pdf/10.1177/0960327110363329

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@article{14dffb6619b54f4cba711daa31a9145a,

title = "Time-response relationship of nano and micro particle induced lung inflammation. Quartz as reference compound",

abstract = "An increasing number of engineered particles, including nanoparticles, are being manufactured, increasing the need for simple low-dose toxicological screening methods. This study aimed to investigate the kinetics of biomarkers related to acute and sub-chronic particle-induced lung inflammation of quartz. Mice were intratracheal instilled with 50 μg of microsized or nanosized quartz. Acute inflammation was assessed 1, 2, 4, 8, 16 or 48 hours post exposure, whereas sub-chronic inflammation was investigated 3 months after exposure. Markers of acute inflammation in the bronchoalveolar lavage fluid (BALF) were neutrophils (PMN), tumor necrosis factor-alfa (TNF-α), interleukin (IL)-1β, macrophage inflammatory protein-2 (MIP-2), keratinocyte derived chemokine (KC) and total protein, which were all close to maximum 16 hours post instillation. No major differences were seen in the time-response profiles of nano- and micro-sized particles. The potency of the two samples cannot be compared; during the milling process, a substantial part of the quartz was converted to amorphous silica and contaminated with corundum. For screening, BALF PMN, either TNF-α or IL-1β at 16 hours post instillation may be useful. At 3 months post instillation, KC, PMN and macrophages were elevated. Histology showed no interstitial inflammation three months post instillation. For screening of sub-chronic effects, KC, PMN, macrophages and histopathology is considered sufficient.",

keywords = "Animals, Bronchoalveolar Lavage Fluid, Cytokines, Dose-Response Relationship, Drug, Female, Inhalation Exposure, Mice, Mice, Inbred BALB C, Microscopy, Electron, Transmission, Nanoparticles, Neutrophils, Particle Size, Pneumonia, Powder Diffraction, Quartz, Surface Properties, Time Factors, Toxicity Tests, X-Ray Diffraction",

author = "Martin Roursgaard and Poulsen, {Steen Seier} and Poulsen, {Lars K.} and Maria Hammer and Jensen, {Keld A.} and Satoshi Utsunomiya and Ewing, {Rodney C.} and {Balic Zunic}, Tonci and Nielsen, {Gunnar D.} and Larsen, {S{\o}ren T.}",

year = "2010",

month = nov,

doi = "10.1177/0960327110363329",

language = "English",

volume = "29",

pages = "915--933",

journal = "Human and Experimental Toxicology",

issn = "0960-3271",

publisher = "SAGE Publications",

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TY - JOUR

T1 - Time-response relationship of nano and micro particle induced lung inflammation. Quartz as reference compound

AU - Roursgaard, Martin

AU - Poulsen, Steen Seier

AU - Poulsen, Lars K.

AU - Hammer, Maria

AU - Jensen, Keld A.

AU - Utsunomiya, Satoshi

AU - Ewing, Rodney C.

AU - Balic Zunic, Tonci

AU - Nielsen, Gunnar D.

AU - Larsen, Søren T.

PY - 2010/11

Y1 - 2010/11

N2 - An increasing number of engineered particles, including nanoparticles, are being manufactured, increasing the need for simple low-dose toxicological screening methods. This study aimed to investigate the kinetics of biomarkers related to acute and sub-chronic particle-induced lung inflammation of quartz. Mice were intratracheal instilled with 50 μg of microsized or nanosized quartz. Acute inflammation was assessed 1, 2, 4, 8, 16 or 48 hours post exposure, whereas sub-chronic inflammation was investigated 3 months after exposure. Markers of acute inflammation in the bronchoalveolar lavage fluid (BALF) were neutrophils (PMN), tumor necrosis factor-alfa (TNF-α), interleukin (IL)-1β, macrophage inflammatory protein-2 (MIP-2), keratinocyte derived chemokine (KC) and total protein, which were all close to maximum 16 hours post instillation. No major differences were seen in the time-response profiles of nano- and micro-sized particles. The potency of the two samples cannot be compared; during the milling process, a substantial part of the quartz was converted to amorphous silica and contaminated with corundum. For screening, BALF PMN, either TNF-α or IL-1β at 16 hours post instillation may be useful. At 3 months post instillation, KC, PMN and macrophages were elevated. Histology showed no interstitial inflammation three months post instillation. For screening of sub-chronic effects, KC, PMN, macrophages and histopathology is considered sufficient.

AB - An increasing number of engineered particles, including nanoparticles, are being manufactured, increasing the need for simple low-dose toxicological screening methods. This study aimed to investigate the kinetics of biomarkers related to acute and sub-chronic particle-induced lung inflammation of quartz. Mice were intratracheal instilled with 50 μg of microsized or nanosized quartz. Acute inflammation was assessed 1, 2, 4, 8, 16 or 48 hours post exposure, whereas sub-chronic inflammation was investigated 3 months after exposure. Markers of acute inflammation in the bronchoalveolar lavage fluid (BALF) were neutrophils (PMN), tumor necrosis factor-alfa (TNF-α), interleukin (IL)-1β, macrophage inflammatory protein-2 (MIP-2), keratinocyte derived chemokine (KC) and total protein, which were all close to maximum 16 hours post instillation. No major differences were seen in the time-response profiles of nano- and micro-sized particles. The potency of the two samples cannot be compared; during the milling process, a substantial part of the quartz was converted to amorphous silica and contaminated with corundum. For screening, BALF PMN, either TNF-α or IL-1β at 16 hours post instillation may be useful. At 3 months post instillation, KC, PMN and macrophages were elevated. Histology showed no interstitial inflammation three months post instillation. For screening of sub-chronic effects, KC, PMN, macrophages and histopathology is considered sufficient.

KW - Animals

KW - Bronchoalveolar Lavage Fluid

KW - Cytokines

KW - Dose-Response Relationship, Drug

KW - Female

KW - Inhalation Exposure

KW - Mice

KW - Mice, Inbred BALB C

KW - Microscopy, Electron, Transmission

KW - Nanoparticles

KW - Neutrophils

KW - Particle Size

KW - Pneumonia

KW - Powder Diffraction

KW - Quartz

KW - Surface Properties

KW - Time Factors

KW - Toxicity Tests

KW - X-Ray Diffraction

U2 - 10.1177/0960327110363329

DO - 10.1177/0960327110363329

M3 - Journal article

C2 - 20237177

SN - 0960-3271

VL - 29

SP - 915

EP - 933

JO - Human and Experimental Toxicology

JF - Human and Experimental Toxicology

IS - 11

ER -

Time-response relationship of nano and micro particle induced lung inflammation. Quartz as reference compound

Abstract

Keywords

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