{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:40:26Z","timestamp":1790548826455,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PETA Science Consortium International e.V."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inhalation is a major route by which human exposure to substances can occur. Resources have therefore been dedicated to optimize human-relevant in vitro approaches that can accurately and efficiently predict the toxicity of inhaled chemicals for robust risk assessment and management. In this study\u2014the IN vitro Systems to PredIct REspiratory toxicity Initiative\u20142 cell-based systems were used to predict the ability of chemicals to cause portal-of-entry effects on the human respiratory tract. A human bronchial epithelial cell line (BEAS-2B) and a reconstructed human tissue model (MucilAir, Epithelix) were exposed to triethoxysilane (TES) and trimethoxysilane (TMS) as vapor (mixed with N2 gas) at the air-liquid interface. Cell viability, cytotoxicity, and secretion of inflammatory markers were assessed in both cell systems and, for MucilAir tissues, morphology, barrier integrity, cilia beating frequency, and recovery after 7\u2009days were also examined. The results show that both cell systems provide valuable information; the BEAS-2B cells were more sensitive in terms of cell viability and inflammatory markers, whereas MucilAir tissues allowed for the assessment of additional cellular effects and time points. As a proof of concept, the data were also used to calculate human equivalent concentrations. As expected, based on chemical properties and existing data, the silanes demonstrated toxicity in both systems with TMS being generally more toxic than TES. Overall, the results demonstrate that these in vitro test systems can provide valuable information relevant to predicting the likelihood of toxicity following inhalation exposure to chemicals in humans.<\/jats:p>","DOI":"10.1093\/toxsci\/kfad074","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T15:23:43Z","timestamp":1690471423000},"page":"213-230","source":"Crossref","is-referenced-by-count":18,"title":["Human cell-based <i>in vitro<\/i> systems to assess respiratory toxicity: a case study using silanes"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2859-2581","authenticated-orcid":false,"given":"Monita","family":"Sharma","sequence":"first","affiliation":[{"name":"PETA Science Consortium International e.V. , 70499 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0997-8502","authenticated-orcid":false,"given":"Andreas O","family":"Stucki","sequence":"additional","affiliation":[{"name":"PETA Science Consortium International e.V. , 70499 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Verstraelen","sequence":"additional","affiliation":[{"name":"Sustainable HEALTH Unit, Flemish Institute for Technological Research (VITO) , BE-2400 Mol, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd J","family":"Stedeford","sequence":"additional","affiliation":[{"name":"The Acta Group , Washington, District of Columbia 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Sustainable HEALTH Unit, Flemish Institute for Technological Research (VITO) , BE-2400 Mol, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Maes","sequence":"additional","affiliation":[{"name":"Sustainable HEALTH Unit, Flemish Institute for Technological Research (VITO) , BE-2400 Mol, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Poelmans","sequence":"additional","affiliation":[{"name":"Sustainable HEALTH Unit, Flemish Institute for Technological Research (VITO) , BE-2400 Mol, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Van Laer","sequence":"additional","affiliation":[{"name":"Sustainable HEALTH Unit, Flemish Institute for Technological Research (VITO) , BE-2400 Mol, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Remy","sequence":"additional","affiliation":[{"name":"Sustainable HEALTH Unit, Flemish Institute for Technological Research (VITO) , BE-2400 Mol, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien","family":"Frijns","sequence":"additional","affiliation":[{"name":"Sustainable HEALTH Unit, Flemish Institute for Technological Research (VITO) , BE-2400 Mol, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G","family":"Allen","sequence":"additional","affiliation":[{"name":"Inotiv, Research Triangle Park , North Carolina 27560, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3623-1196","authenticated-orcid":false,"given":"Amy J","family":"Clippinger","sequence":"additional","affiliation":[{"name":"PETA Science Consortium International e.V. , 70499 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"2023092810510599100_kfad074-B1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.tox.2007.11.001","article-title":"An in vitro approach to assess the toxicity of inhaled tobacco smoke components: Nicotine, cadmium, formaldehyde and urethane","volume":"244","author":"Balharry","year":"2008","journal-title":"Toxicology"},{"key":"2023092810510599100_kfad074-B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting linear mixed-effects models using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J. 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