Physical Obstruction of Nasal Cavities With Subsequent Asphyxia, Causes Lethality of Rats in an Acute Inhalation Study With Hydrophobic HMDZ Surface-Treated Synthetic Amorphous Silica (SAS)

The aim of the present study was to understand the mechanism of lethality associated with high dose inhalation of a low-density hydrophobic surface-treated SAS observed in some acute inhalation studies. It was demonstrated that physical obstruction of the upper respiratory tract (nasal cavities) cau...

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Main Authors: Nils Krueger, Klaus Weber, Nils Warfving, Alex Vitali, Jürgen Nolde, Tobias B. Schuster, Gustav Gerd Bruer, Otto Creutzenberg, Benno Wessely, Michael Stintz, Valerie Moise, Marco Kellert
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Public Health
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Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2022.907078/full
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author Nils Krueger
Klaus Weber
Nils Warfving
Alex Vitali
Jürgen Nolde
Tobias B. Schuster
Gustav Gerd Bruer
Otto Creutzenberg
Benno Wessely
Michael Stintz
Valerie Moise
Marco Kellert
author_facet Nils Krueger
Klaus Weber
Nils Warfving
Alex Vitali
Jürgen Nolde
Tobias B. Schuster
Gustav Gerd Bruer
Otto Creutzenberg
Benno Wessely
Michael Stintz
Valerie Moise
Marco Kellert
author_sort Nils Krueger
collection DOAJ
description The aim of the present study was to understand the mechanism of lethality associated with high dose inhalation of a low-density hydrophobic surface-treated SAS observed in some acute inhalation studies. It was demonstrated that physical obstruction of the upper respiratory tract (nasal cavities) caused the effects observed. Hydrophobic surface-treated SAS was inhaled (flow-past, nose-only) by six Wistar rats (three males and three females) in an acute toxicity study at a concentration of ~500 mg/m3 for an intended 4-hr exposure. Under the conditions of the test set-up, the concentration applied was found to be the highest that can be delivered to the test animal port without significant alteration of the aerosol size distribution over time. None of the test- material-exposed animals survived the planned observation time of 4 h; three animals died between 234 h after starting exposure and cessation of exposure at 314 h, two died after transfer to their cages and the remaining animal was sacrificed due to its poor condition and welfare considerations. Histology accomplished by energy dispersive X-ray (EDX) analysis demonstrated that test material particles agglomerated and formed a gel-like substrate that ultimately blocked the upper respiratory airways, which proved fatal for the rat as an obligatory nose breather. This observation is in line with the findings reported by Hofmann et al. showing a correlation between lethality and hydrophobicity determined by contact angle measurement. The aerosol characterizations associated with this study are provided in detail by Wessely et al.
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spelling doaj.art-c5056b066fbe484f83b540b6b14ee8bc2022-12-22T00:14:41ZengFrontiers Media S.A.Frontiers in Public Health2296-25652022-06-011010.3389/fpubh.2022.907078907078Physical Obstruction of Nasal Cavities With Subsequent Asphyxia, Causes Lethality of Rats in an Acute Inhalation Study With Hydrophobic HMDZ Surface-Treated Synthetic Amorphous Silica (SAS)Nils Krueger0Klaus Weber1Nils Warfving2Alex Vitali3Jürgen Nolde4Tobias B. Schuster5Gustav Gerd Bruer6Otto Creutzenberg7Benno Wessely8Michael Stintz9Valerie Moise10Marco Kellert11Evonik Operations GmbH, Smart Materials, Hanau, GermanyAnaPath Services GmbH, Liestal, SwitzerlandAnaPath Services GmbH, Liestal, SwitzerlandAnaPath Services GmbH, Liestal, SwitzerlandGrace Europe Holding GmbH, Worms, GermanyEvonik Operations GmbH, Smart Materials, Hanau, GermanyDepartment of Inhalation Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine (Fh-ITEM), Hannover, GermanyDepartment of Inhalation Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine (Fh-ITEM), Hannover, GermanyInstitute of Process Engineering and Environmental Technology, Research Group Mechanical Process Engineering, Technische Universität Dresden, Dresden, GermanyInstitute of Process Engineering and Environmental Technology, Research Group Mechanical Process Engineering, Technische Universität Dresden, Dresden, GermanyCabot Corporation, Corporate SHE - Product Safety and Toxicology, Loncin, BelgiumWacker Chemie AG, Burghausen, GermanyThe aim of the present study was to understand the mechanism of lethality associated with high dose inhalation of a low-density hydrophobic surface-treated SAS observed in some acute inhalation studies. It was demonstrated that physical obstruction of the upper respiratory tract (nasal cavities) caused the effects observed. Hydrophobic surface-treated SAS was inhaled (flow-past, nose-only) by six Wistar rats (three males and three females) in an acute toxicity study at a concentration of ~500 mg/m3 for an intended 4-hr exposure. Under the conditions of the test set-up, the concentration applied was found to be the highest that can be delivered to the test animal port without significant alteration of the aerosol size distribution over time. None of the test- material-exposed animals survived the planned observation time of 4 h; three animals died between 234 h after starting exposure and cessation of exposure at 314 h, two died after transfer to their cages and the remaining animal was sacrificed due to its poor condition and welfare considerations. Histology accomplished by energy dispersive X-ray (EDX) analysis demonstrated that test material particles agglomerated and formed a gel-like substrate that ultimately blocked the upper respiratory airways, which proved fatal for the rat as an obligatory nose breather. This observation is in line with the findings reported by Hofmann et al. showing a correlation between lethality and hydrophobicity determined by contact angle measurement. The aerosol characterizations associated with this study are provided in detail by Wessely et al.https://www.frontiersin.org/articles/10.3389/fpubh.2022.907078/fullsynthetic amorphous silicainhalationratcontact anglephysical obstructionsuffocation
spellingShingle Nils Krueger
Klaus Weber
Nils Warfving
Alex Vitali
Jürgen Nolde
Tobias B. Schuster
Gustav Gerd Bruer
Otto Creutzenberg
Benno Wessely
Michael Stintz
Valerie Moise
Marco Kellert
Physical Obstruction of Nasal Cavities With Subsequent Asphyxia, Causes Lethality of Rats in an Acute Inhalation Study With Hydrophobic HMDZ Surface-Treated Synthetic Amorphous Silica (SAS)
Frontiers in Public Health
synthetic amorphous silica
inhalation
rat
contact angle
physical obstruction
suffocation
title Physical Obstruction of Nasal Cavities With Subsequent Asphyxia, Causes Lethality of Rats in an Acute Inhalation Study With Hydrophobic HMDZ Surface-Treated Synthetic Amorphous Silica (SAS)
title_full Physical Obstruction of Nasal Cavities With Subsequent Asphyxia, Causes Lethality of Rats in an Acute Inhalation Study With Hydrophobic HMDZ Surface-Treated Synthetic Amorphous Silica (SAS)
title_fullStr Physical Obstruction of Nasal Cavities With Subsequent Asphyxia, Causes Lethality of Rats in an Acute Inhalation Study With Hydrophobic HMDZ Surface-Treated Synthetic Amorphous Silica (SAS)
title_full_unstemmed Physical Obstruction of Nasal Cavities With Subsequent Asphyxia, Causes Lethality of Rats in an Acute Inhalation Study With Hydrophobic HMDZ Surface-Treated Synthetic Amorphous Silica (SAS)
title_short Physical Obstruction of Nasal Cavities With Subsequent Asphyxia, Causes Lethality of Rats in an Acute Inhalation Study With Hydrophobic HMDZ Surface-Treated Synthetic Amorphous Silica (SAS)
title_sort physical obstruction of nasal cavities with subsequent asphyxia causes lethality of rats in an acute inhalation study with hydrophobic hmdz surface treated synthetic amorphous silica sas
topic synthetic amorphous silica
inhalation
rat
contact angle
physical obstruction
suffocation
url https://www.frontiersin.org/articles/10.3389/fpubh.2022.907078/full
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