{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T07:51:43Z","timestamp":1782546703992,"version":"3.54.5"},"reference-count":106,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T00:00:00Z","timestamp":1712966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P42 ES016465"],"award-info":[{"award-number":["P42 ES016465"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P30 ES030287"],"award-info":[{"award-number":["P30 ES030287"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["T32 ES07060"],"award-info":[{"award-number":["T32 ES07060"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>One of the most significant challenges in human health risk assessment is to evaluate hazards from exposure to environmental chemical mixtures. Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous contaminants typically found as mixtures in gaseous and particulate phases in ambient air pollution associated with petrochemicals from Superfund sites and the burning of fossil fuels. However, little is understood about how PAHs in mixtures contribute to toxicity in lung cells. To investigate mixture interactions and component additivity from environmentally relevant PAHs, two synthetic mixtures were created from PAHs identified in passive air samplers at a legacy creosote site impacted by wildfires. The primary human bronchial epithelial cells differentiated at the air\u2013liquid interface were treated with PAH mixtures at environmentally relevant proportions and evaluated for the differential expression of transcriptional biomarkers related to xenobiotic metabolism, oxidative stress response, barrier integrity, and DNA damage response. Component additivity was evaluated across all endpoints using two independent action (IA) models with and without the scaling of components by toxic equivalence factors. Both IA models exhibited trends that were unlike the observed mixture response and generally underestimated the toxicity across dose suggesting the potential for non-additive interactions of components. Overall, this study provides an example of the usefulness of mixture toxicity assessment with the currently available methods while demonstrating the need for more complex yet interpretable mixture response evaluation methods for environmental samples.<\/jats:p>","DOI":"10.3390\/ijms25084326","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T10:24:26Z","timestamp":1713176666000},"page":"4326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Modeling PAH Mixture Interactions in a Human In Vitro Organotypic Respiratory Model"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9656-4801","authenticated-orcid":false,"given":"Victoria C.","family":"Colvin","sequence":"first","affiliation":[{"name":"Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA"},{"name":"OSU\/PNNL Superfund Research Program, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8384-1926","authenticated-orcid":false,"given":"Lisa M.","family":"Bramer","sequence":"additional","affiliation":[{"name":"OSU\/PNNL Superfund Research Program, Oregon State University, Corvallis, OR 97331, USA"},{"name":"Pacific Northwest National Laboratory, Richland, WA 99352, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna N.","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA"},{"name":"OSU\/PNNL Superfund Research Program, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie M.","family":"Pennington","sequence":"additional","affiliation":[{"name":"Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina M.","family":"Waters","sequence":"additional","affiliation":[{"name":"OSU\/PNNL Superfund Research Program, Oregon State University, Corvallis, OR 97331, USA"},{"name":"Pacific Northwest National Laboratory, Richland, WA 99352, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5427-6462","authenticated-orcid":false,"given":"Susan C.","family":"Tilton","sequence":"additional","affiliation":[{"name":"Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA"},{"name":"OSU\/PNNL Superfund Research Program, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47844","DOI":"10.1039\/C6RA05406D","article-title":"Risk assessment of environmental mixture effects","volume":"6","author":"Heys","year":"2016","journal-title":"RSC Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s12302-021-00565-0","article-title":"Options for an environmental risk assessment of intentional and unintentional chemical mixtures under REACH: The status and ways forward","volume":"33","author":"Hassold","year":"2021","journal-title":"Environ. 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