{"doi":"10.1093/toxsci/kfac113","title":"Aerosol physicochemical determinants of carbon black and ozone inhalation co-exposure induced pulmonary toxicity","abstract":"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 h 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 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-1β, 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.","journal":"Toxicological Sciences","year":2022,"id":255828,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9449,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":368819,"name":"Vamsi Kodali","orcid":"0000-0001-6177-0568","position":1,"is_corresponding":false},{"id":313064,"name":"Murugesan Velayutham","orcid":null,"position":2,"is_corresponding":false},{"id":904639,"name":"Travis Goldsmith","orcid":null,"position":3,"is_corresponding":false},{"id":749853,"name":"Jessica Amedro","orcid":"0000-0001-5759-8910","position":4,"is_corresponding":false},{"id":430911,"name":"Valery V. Khramtsov","orcid":"0000-0001-6187-5546","position":5,"is_corresponding":false},{"id":368821,"name":"Aaron Erdely","orcid":"0000-0002-2557-1673","position":6,"is_corresponding":false},{"id":411603,"name":"Timothy R. Nurkiewicz","orcid":"0000-0001-9105-970X","position":7,"is_corresponding":false},{"id":313892,"name":"Jack R. Harkema","orcid":"0000-0003-4682-0824","position":8,"is_corresponding":false},{"id":247931,"name":"Eric E. Kelley","orcid":"0000-0002-0393-1498","position":9,"is_corresponding":false},{"id":292268,"name":"Salik Hussain","orcid":"0000-0003-0339-6226","position":10,"is_corresponding":false},{"id":667508,"name":"Nairrita Majumder","orcid":"0000-0002-7297-7019","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T00:25:17.224217Z","pmid":"36303316","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}