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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\u2009mg\/m3), O3 (0.5, 1.0, 2.0\u2009ppm) with mixture CB + O3 (2.5\u2009+\u20090.5, 5.0\u2009+\u20091.0, 10.0\u2009+\u20092.0). C57BL6 male mice were exposed for 3\u2009h by whole body inhalation and acute toxicity determined after 24\u2009h. 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 was due to enhanced reactivity of the particles. Benchmark dose modeling showed several-fold increase in potency with CB + O3 compared with 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 (interleukin-1\u03b2, keratinocyte chemoattractant, transforming growth factor beta) or particle reactivity (thymic stromal lymphopoietin, interleukin-13, interleukin-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.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac113","type":"journal-article","created":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T04:54:17Z","timestamp":1666932857000},"page":"61-78","source":"Crossref","is-referenced-by-count":21,"title":["Aerosol physicochemical determinants of carbon black and ozone inhalation co-exposure induced pulmonary toxicity"],"prefix":"10.1093","volume":"191","author":[{"given":"Nairrita","family":"Majumder","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, School of Medicine, West Virginia University , Morgantown, West Virginia 26506, USA"},{"name":"Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University , Morgantown, West Virginia 26506, 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University , Morgantown, West Virginia 26506, USA"},{"name":"Department of Biochemistry and Molecular Medicine, School of Medicine, West Virginia University , Morgantown, West Virginia 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, School of Medicine, West Virginia University , Morgantown, West Virginia 26506, USA"},{"name":"Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University , Morgantown, West Virginia 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Amedro","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, School of Medicine, West Virginia University , Morgantown, West Virginia 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery V","family":"Khramtsov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, School of Medicine, West Virginia University , Morgantown, West Virginia 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Erdely","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, School of Medicine, West Virginia University , Morgantown, West Virginia 26506, USA"},{"name":"Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University , Morgantown, West Virginia 26506, USA"},{"name":"Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH) , Morgantown, West Virginia 26508, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R","family":"Nurkiewicz","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, School of Medicine, West Virginia University , Morgantown, West Virginia 26506, USA"},{"name":"Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University , Morgantown, West Virginia 26506, USA"},{"name":"Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH) , Morgantown, West Virginia 26508, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack R","family":"Harkema","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University , East Lansing, Michigan 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric E","family":"Kelley","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, School of Medicine, West Virginia University , Morgantown, West Virginia 26506, USA"},{"name":"Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University , Morgantown, West 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