Aerosol Physicochemical Determinants of Carbon Black and Ozone Inhalation Co-Exposure Induced Pulmonary Toxicity
Public Domain
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2023/01/01
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Details
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Personal Author:Amedro J ; Erdely A ; Goldsmith T ; Harkema JR ; Hussain S ; Kelley EE ; Khramtsov VV ; Kodali V ; Majumder N ; Nurkiewicz TR ; Velayutham M
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Description:Air pollution accounts for more than 7 million premature deaths worldwide. Using ultrafine carbon black (CB) and ozone (O3) as a model for an environmental co-exposure scenario, the dose response relationships in acute pulmonary injury and inflammation were determined by generating, characterizing, and comparing stable concentrations of CB aerosols (2.5, 5.0, 10.0 mg/m3), O3 (0.5, 1.0, 2.0 ppm) with mixture CB+O3 (2.5 + 0.5, 5.0 + 1.0, 10.0 + 2.0). C57BL6 male mice were exposed for 3 hours by whole body inhalation and acute toxicity determined after 24 h. CB itself did not cause any alteration, however, a dose response in pulmonary injury/inflammation was observed with O3 and CB+O3. This increase in response with mixtures was not dependent on the uptake but due to enhanced reactivity of the particles. Benchmark dose modeling showed several-fold increase in potency with CB+O3 compared to CB or O3 alone. Principal component analysis provided insight into response relationships between various doses and treatments. There was a significant correlation in lung responses with charge-based size distribution, total/alveolar deposition, oxidant generation and antioxidant depletion potential. Lung tissue gene/protein response demonstrated distinct patterns that are better predicted by either particle dose/aerosol responses (IL-1beta, KC, TGF-beta) or particle reactivity (TSLP, IL13, IL-6). Hierarchical clustering showed a distinct signature with high dose and a similarity in mRNA expression pattern of low and medium doses of CB+O3. In conclusion, we demonstrate that the biological outcomes from CB+O3 co-exposure are significantly greater than individual exposures over a range of aerosol concentrations and aerosol characteristics can predict biological outcome. [Description provided by NIOSH]
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ISSN:1096-6080
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Pages in Document:61-78
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Volume:191
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Issue:1
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NIOSHTIC Number:nn:20066392
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Citation:Toxicol Sci 2023 Jan; 191(1):61-78
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Contact Point Address:Salik Hussain, Department of Physiology and Pharmacology, Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University, Morgantown, WV 26506, USA
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Email:salik.hussain@hsc.wvu.edu
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Federal Fiscal Year:2023
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Peer Reviewed:True
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Source Full Name:Toxicological Sciences
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Main Document Checksum:urn:sha-512:22412dc19b1bf39ab0868dae8cf605a411bd80a555de10f56ec3556c0596360d6c33282eb4a42c3deb016a54b0bb6decd4b2c23a5ae03e786e1cbff5787eefd7
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