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Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties
Ulla B Vogel
National Research Centre for the Working Environment
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6807-1524
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This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Particle and Fibre Toxicology.
Background Diesel exhaust is carcinogenic and exposure to diesel particles cause health effects. We investigated the toxicity of diesel exhaust particles designed to have varying physicochemical properties in order to attribute health effects to specific particle characteristics. Particles from three fuel types were compared at 13% engine intake O 2 concentration: MK1 ultra low sulfur diesel (DEP13) and the two renewable diesel fuels hydrotreated vegetable oil (HVO13) and rapeseed methyl ester (RME13). Additionally, diesel particles from MK1 ultra low sulfur diesel were generated at 9.7% (DEP9.7) and 17% (DEP17) intake O 2 concentration. We evaluated physicochemical properties and histopathological, inflammatory and genotoxic responses on day 1, 28, and 90 after single intratracheal instillation in mice compared to reference diesel particles and carbon black.
Results Moderate variations were seen in physical properties for the five particles: primary particle diameter: 15-22 nm, specific surface area: 152-222 m 2 /g, and count median mobility diameter: 55-103 nm. Larger differences were found in chemical composition: organic carbon/total carbon ratio (0.12-0.60), polycyclic aromatic hydrocarbon content (1-27 mg/mg) and acid-extractable metal content (0.9-16 mg/mg). Intratracheal exposure to all five particles induced similar toxicological responses, with different potency. Lung particle retention was observed in DEP13 and HVO13 exposed mice on day 28 post-exposure, with less retention for the other fuel types. RME exposure induced limited response whereas the remaining particles induced dose-dependent inflammation and acute phase response on day 1. DEP13 induced acute phase response on day 28 and inflammation on day 90. DNA strand break levels were not increased as compared to vehicle, but were increased in lung and liver compared to blank filter extraction control. Neutrophil influx on day 1 correlated best with estimated deposited surface area, but also with elemental carbon, organic carbon and PAHs. DNA strand break levels in lung on day 28 and in liver on day 90 correlated with acellular particle-induced ROS.
Conclusions We studied diesel exhaust particles designed to differ in physicochemical properties. Our study highlights specific surface area, elemental carbon content, PAHs and ROS-generating potential as physicochemical predictors of diesel particle toxicity.
Keywords
Diesel exhaust particles, Ultrafine particles, Toxicity, Intratracheal instillation, Exhaust gas recirculation, Renewable diesel fuels
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CURRENT STATUS: Published
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Received 17 Jul, 2020
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On 14 Jul, 2020
Reviewer #3 agreed
On 14 Jul, 2020
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On 14 Jul, 2020
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On 14 Jul, 2020
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Received 14 Jul, 2020
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On 13 Jul, 2020
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On 13 Jul, 2020
No comments provided
Review #3 received
Received 18 Jun, 2020
Editorial decision: Major Revision
On 18 Jun, 2020
Review #2 received
Received 01 Jun, 2020
Reviewer #3 agreed
On 22 May, 2020
Reviewer #2 agreed
On 11 May, 2020
Review #1 received
Received 16 Apr, 2020
Reviewers invited
Invitations sent on 01 Apr, 2020
Reviewer #1 agreed
On 01 Apr, 2020
Editor assigned
On 24 Mar, 2020
Submission checks complete
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This preprint is under consideration at Particle and Fibre Toxicology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties
Ulla B Vogel
National Research Centre for the Working Environment
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6807-1524
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 15 Jul, 2020
Published
On 08 Aug, 2020
No community comments so far
Editorial decision: Accept
On 20 Jul, 2020
Review #3 received
Received 17 Jul, 2020
Review #2 received
Received 17 Jul, 2020
Reviewer #2 agreed
On 14 Jul, 2020
Reviewer #3 agreed
On 14 Jul, 2020
Editor assigned
On 14 Jul, 2020
Reviewers invited
Invitations sent on 14 Jul, 2020
Reviewer #1 agreed
On 14 Jul, 2020
Review #1 received
Received 14 Jul, 2020
Submission checks complete
On 13 Jul, 2020
Editor invited
On 13 Jul, 2020
No comments provided
Review #3 received
Received 18 Jun, 2020
Editorial decision: Major Revision
On 18 Jun, 2020
Review #2 received
Received 01 Jun, 2020
Reviewer #3 agreed
On 22 May, 2020
Reviewer #2 agreed
On 11 May, 2020
Review #1 received
Received 16 Apr, 2020
Reviewers invited
Invitations sent on 01 Apr, 2020
Reviewer #1 agreed
On 01 Apr, 2020
Editor assigned
On 24 Mar, 2020
Submission checks complete
On 23 Mar, 2020
Editor invited
On 23 Mar, 2020
First submitted
On 20 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Toxicology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Particle and Fibre Toxicology.
Background Diesel exhaust is carcinogenic and exposure to diesel particles cause health effects. We investigated the toxicity of diesel exhaust particles designed to have varying physicochemical properties in order to attribute health effects to specific particle characteristics. Particles from three fuel types were compared at 13% engine intake O 2 concentration: MK1 ultra low sulfur diesel (DEP13) and the two renewable diesel fuels hydrotreated vegetable oil (HVO13) and rapeseed methyl ester (RME13). Additionally, diesel particles from MK1 ultra low sulfur diesel were generated at 9.7% (DEP9.7) and 17% (DEP17) intake O 2 concentration. We evaluated physicochemical properties and histopathological, inflammatory and genotoxic responses on day 1, 28, and 90 after single intratracheal instillation in mice compared to reference diesel particles and carbon black.
Results Moderate variations were seen in physical properties for the five particles: primary particle diameter: 15-22 nm, specific surface area: 152-222 m 2 /g, and count median mobility diameter: 55-103 nm. Larger differences were found in chemical composition: organic carbon/total carbon ratio (0.12-0.60), polycyclic aromatic hydrocarbon content (1-27 mg/mg) and acid-extractable metal content (0.9-16 mg/mg). Intratracheal exposure to all five particles induced similar toxicological responses, with different potency. Lung particle retention was observed in DEP13 and HVO13 exposed mice on day 28 post-exposure, with less retention for the other fuel types. RME exposure induced limited response whereas the remaining particles induced dose-dependent inflammation and acute phase response on day 1. DEP13 induced acute phase response on day 28 and inflammation on day 90. DNA strand break levels were not increased as compared to vehicle, but were increased in lung and liver compared to blank filter extraction control. Neutrophil influx on day 1 correlated best with estimated deposited surface area, but also with elemental carbon, organic carbon and PAHs. DNA strand break levels in lung on day 28 and in liver on day 90 correlated with acellular particle-induced ROS.
Conclusions We studied diesel exhaust particles designed to differ in physicochemical properties. Our study highlights specific surface area, elemental carbon content, PAHs and ROS-generating potential as physicochemical predictors of diesel particle toxicity.
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