Academic Journal
In vitro approaches to assess respiratory toxicity from volatile organic compounds: an in-depth review.
| Τίτλος: | In vitro approaches to assess respiratory toxicity from volatile organic compounds: an in-depth review. |
|---|---|
| Συγγραφείς: | Lampe OCG; Department of Environmental and Occupational Health, Interdisciplinary Program in Toxicology, Texas A&M University, College Station, TX 77843, United States., Vitucci ECM; Department of Environmental and Occupational Health, Interdisciplinary Program in Toxicology, Texas A&M University, College Station, TX 77843, United States., Cannon CL; Department of Microbial Pathogenesis and Immunology, Texas A&M University, College Station, TX 77843, United States., Holland K; Medical Sciences Library, Texas A&M University, College Station, TX 77843, United States., Foster MJ; Medical Sciences Library, Texas A&M University, College Station, TX 77843, United States., Johnson NM; Department of Environmental and Occupational Health, Interdisciplinary Program in Toxicology, Texas A&M University, College Station, TX 77843, United States. |
| Πηγή: | Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2026 Sep 02; Vol. 209 (9). |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 9805461 Publication Model: Print Cited Medium: Internet ISSN: 1096-0929 (Electronic) Linking ISSN: 10960929 NLM ISO Abbreviation: Toxicol Sci Subsets: MEDLINE |
| Imprint Name(s): | Publication: 1999- : Cary, NC : Oxford University Press Original Publication: Orlando, FL : Academic Press, c1998- |
| Ιατρικοί όροι (MeSH): | Volatile Organic Compounds*/toxicity , Air Pollutants*/toxicity , Toxicity Tests*/methods , Lung*/drug effects , Lung*/metabolism , Lung*/pathology , Epithelial Cells*/drug effects , Epithelial Cells*/metabolism , Epithelial Cells*/pathology, Oxidative Stress/drug effects ; Inhalation Exposure/adverse effects ; Humans ; Animals |
| Περίληψη: | Volatile organic compounds (VOCs) are ubiquitous inhaled pollutants. This review showcases current literature utilizing in vitro models of the human respiratory system to characterize the toxicity of VOCs. To map the existing evidence base, we conducted a scoping review following systematic search and screening procedures. Comprehensive searches of MEDLINE, Embase, Web of Science, CINAHL, PubMed, and CENTRAL identified 3,052 records. After screening, 144 original studies evaluating VOC exposures in human lung epithelial models met inclusion criteria. Overall, the current literature reflects substantial heterogeneity in cell models, exposure systems, and endpoints. Among 105 unique VOCs evaluated, acrolein, formaldehyde, toluene diisocyanate, and benzene were most frequently studied. Most investigations used submerged culture systems with liquid-phase VOC application, whereas fewer employed air-liquid interface (ALI) exposures that better mimic inhalation. Cytotoxicity, oxidative stress, proinflammatory signaling, and apoptosis were the most commonly measured endpoints, with oxidative stress frequently identified as an upstream driver of inflammatory and cytotoxic responses. However, mechanistic depth varied, and studies examining metabolism, barrier function, morphology, or transcriptomic regulation were relatively uncommon. Notably, chronic or repeated exposures were rarely conducted. Overall, this review highlights the variety of VOC exposure methods and commonly assessed biological endpoints, as well as the critical lack of more detailed mechanistic studies and somewhat limited VOC/mixture evaluation. The field is expansive but methodologically fragmented, underscoring the need for broader use of human respiratory cell models, more physiologically relevant exposure systems, improved dose characterization, and greater mechanistic resolution to advance understanding and throughput for VOC-induced pulmonary toxicity studies. (© The Author(s) 2026. Published by Oxford University Press on behalf of the Society of Toxicology.) |
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| Grant Information: | P30 ES029067 United States ES NIEHS NIH HHS; P42 ES027704 United States ES NIEHS NIH HHS |
| Contributed Indexing: | Keywords: air–liquid interface culture; dose characterization; human lung epithelial cells; oxidative stress; submerged cell culture |
| Substance Nomenclature: | 0 (Volatile Organic Compounds) 0 (Air Pollutants) |
| Entry Date(s): | Date Created: 20260820 Date Completed: 20260909 Latest Revision: 20260912 |
| Update Code: | 20260912 |
| PubMed Central ID: | PMC13557630 |
| DOI: | 10.1093/toxsci/kfag110 |
| PMID: | 42623132 |
| Βάση Δεδομένων: | MEDLINE |
| FullText | Links: – Type: other Url: https://resolver.ebsco.com:443/public/rma-ftfapi/ejs/direct?AccessToken=4FE3BCA6D8AC59B436A1&Show=Object Text: Availability: 0 |
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| Header | DbId: cmedm DbLabel: MEDLINE An: 42623132 AccessLevel: 3 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: In vitro approaches to assess respiratory toxicity from volatile organic compounds: an in-depth review. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AU" term="%22Lampe+OCG%22">Lampe OCG</searchLink>; Department of Environmental and Occupational Health, Interdisciplinary Program in Toxicology, Texas A&M University, College Station, TX 77843, United States.<br /><searchLink fieldCode="AU" term="%22Vitucci+ECM%22">Vitucci ECM</searchLink>; Department of Environmental and Occupational Health, Interdisciplinary Program in Toxicology, Texas A&M University, College Station, TX 77843, United States.<br /><searchLink fieldCode="AU" term="%22Cannon+CL%22">Cannon CL</searchLink>; Department of Microbial Pathogenesis and Immunology, Texas A&M University, College Station, TX 77843, United States.<br /><searchLink fieldCode="AU" term="%22Holland+K%22">Holland K</searchLink>; Medical Sciences Library, Texas A&M University, College Station, TX 77843, United States.<br /><searchLink fieldCode="AU" term="%22Foster+MJ%22">Foster MJ</searchLink>; Medical Sciences Library, Texas A&M University, College Station, TX 77843, United States.<br /><searchLink fieldCode="AU" term="%22Johnson+NM%22">Johnson NM</searchLink>; Department of Environmental and Occupational Health, Interdisciplinary Program in Toxicology, Texas A&M University, College Station, TX 77843, United States. – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%229805461%22">Toxicological sciences : an official journal of the Society of Toxicology</searchLink> [Toxicol Sci] 2026 Sep 02; Vol. 209 (9). – Name: TypePub Label: Publication Type Group: TypPub Data: Journal Article; Review – Name: Language Label: Language Group: Lang Data: English – Name: TitleSource Label: Journal Info Group: Src Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Oxford+University+Press%22">Oxford University Press </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>9805461 <i>Publication Model: </i>Print <i>Cited Medium: </i>Internet <i>ISSN: </i>1096-0929 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2210960929%22">10960929 </searchLink><i>NLM ISO Abbreviation: </i>Toxicol Sci <i>Subsets: </i>MEDLINE – Name: PublisherInfo Label: Imprint Name(s) Group: PubInfo Data: <i>Publication</i>: 1999- : Cary, NC : Oxford University Press<br /><i>Original Publication</i>: Orlando, FL : Academic Press, c1998- – Name: SubjectMESH Label: MeSH Terms Group: Su Data: <searchLink fieldCode="MM" term="%22Volatile+Organic+Compounds%22">Volatile Organic Compounds*</searchLink>/<searchLink fieldCode="MM" term="%22Volatile+Organic+Compounds+toxicity%22">toxicity</searchLink> <br /><searchLink fieldCode="MM" term="%22Air+Pollutants%22">Air Pollutants*</searchLink>/<searchLink fieldCode="MM" term="%22Air+Pollutants+toxicity%22">toxicity</searchLink> <br /><searchLink fieldCode="MM" term="%22Toxicity+Tests%22">Toxicity Tests*</searchLink>/<searchLink fieldCode="MM" term="%22Toxicity+Tests+methods%22">methods</searchLink> <br /><searchLink fieldCode="MM" term="%22Lung%22">Lung*</searchLink>/<searchLink fieldCode="MM" term="%22Lung+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Lung%22">Lung*</searchLink>/<searchLink fieldCode="MM" term="%22Lung+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Lung%22">Lung*</searchLink>/<searchLink fieldCode="MM" term="%22Lung+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Epithelial+Cells%22">Epithelial Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Epithelial+Cells+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Epithelial+Cells%22">Epithelial Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Epithelial+Cells+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Epithelial+Cells%22">Epithelial Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Epithelial+Cells+pathology%22">pathology</searchLink><br /><searchLink fieldCode="MH" term="%22Oxidative+Stress%22">Oxidative Stress</searchLink>/<searchLink fieldCode="MH" term="%22Oxidative+Stress+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Inhalation+Exposure%22">Inhalation Exposure</searchLink>/<searchLink fieldCode="MH" term="%22Inhalation+Exposure+adverse+effects%22">adverse effects</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Volatile organic compounds (VOCs) are ubiquitous inhaled pollutants. This review showcases current literature utilizing in vitro models of the human respiratory system to characterize the toxicity of VOCs. To map the existing evidence base, we conducted a scoping review following systematic search and screening procedures. Comprehensive searches of MEDLINE, Embase, Web of Science, CINAHL, PubMed, and CENTRAL identified 3,052 records. After screening, 144 original studies evaluating VOC exposures in human lung epithelial models met inclusion criteria. Overall, the current literature reflects substantial heterogeneity in cell models, exposure systems, and endpoints. Among 105 unique VOCs evaluated, acrolein, formaldehyde, toluene diisocyanate, and benzene were most frequently studied. Most investigations used submerged culture systems with liquid-phase VOC application, whereas fewer employed air-liquid interface (ALI) exposures that better mimic inhalation. Cytotoxicity, oxidative stress, proinflammatory signaling, and apoptosis were the most commonly measured endpoints, with oxidative stress frequently identified as an upstream driver of inflammatory and cytotoxic responses. However, mechanistic depth varied, and studies examining metabolism, barrier function, morphology, or transcriptomic regulation were relatively uncommon. Notably, chronic or repeated exposures were rarely conducted. Overall, this review highlights the variety of VOC exposure methods and commonly assessed biological endpoints, as well as the critical lack of more detailed mechanistic studies and somewhat limited VOC/mixture evaluation. The field is expansive but methodologically fragmented, underscoring the need for broader use of human respiratory cell models, more physiologically relevant exposure systems, improved dose characterization, and greater mechanistic resolution to advance understanding and throughput for VOC-induced pulmonary toxicity studies.<br /> (© The Author(s) 2026. Published by Oxford University Press on behalf of the Society of Toxicology.) – Name: Ref Label: References Group: RefInfo Data: Free Radic Biol Med. 2002 Aug 15;33(4):464-72. (PMID: <searchLink fieldCode="PM" term="%2212160929%22">12160929)</searchLink><br />Br J Ind Med. 1991 Jul;48(7):437-44. (PMID: <searchLink fieldCode="PM" term="%221854646%22">1854646)</searchLink><br />Chem Res Toxicol. 2008 Dec;21(12):2245-56. (PMID: <searchLink fieldCode="PM" term="%2219548348%22">19548348)</searchLink><br />J Toxicol Environ Health A. 2004 Mar 12;67(5):421-30. (PMID: <searchLink fieldCode="PM" term="%2214718178%22">14718178)</searchLink><br />Adv Exp Med Biol. 2021;1304:187-204. (PMID: <searchLink fieldCode="PM" term="%2234019270%22">34019270)</searchLink><br />Biosci Rep. 2020 Oct 30;40(10):. (PMID: <searchLink fieldCode="PM" term="%2232985670%22">32985670)</searchLink><br />Int J Environ Res Public Health. 2021 Feb 07;18(4):. (PMID: <searchLink fieldCode="PM" term="%2233562372%22">33562372)</searchLink><br />Front Public Health. 2023 Jul 05;11:1210136. (PMID: <searchLink fieldCode="PM" term="%2237475768%22">37475768)</searchLink><br />Tumour Biol. 2016 Jul;37(7):8471-86. (PMID: <searchLink fieldCode="PM" term="%2227059734%22">27059734)</searchLink><br />Am J Respir Cell Mol Biol. 2014 Sep;51(3):426-35. (PMID: <searchLink fieldCode="PM" term="%2224693990%22">24693990)</searchLink><br />Antioxid Redox Signal. 2010 Mar;12(3):323-5. (PMID: <searchLink fieldCode="PM" term="%2219743917%22">19743917)</searchLink><br />Am J Physiol Lung Cell Mol Physiol. 2015 Apr 15;308(8):L731-45. (PMID: <searchLink fieldCode="PM" term="%2225637609%22">25637609)</searchLink><br />Environ Res. 2025 Aug 15;279(Pt 2):121856. (PMID: <searchLink fieldCode="PM" term="%2240379004%22">40379004)</searchLink><br />PLoS One. 2016 Oct 25;11(10):e0165225. (PMID: <searchLink fieldCode="PM" term="%2227780255%22">27780255)</searchLink><br />Methods Mol Biol. 2024;2808:141-152. (PMID: <searchLink fieldCode="PM" term="%2238743368%22">38743368)</searchLink><br />Toxicol Sci. 1999 Jul;50(1):64-71. (PMID: <searchLink fieldCode="PM" term="%2210445754%22">10445754)</searchLink><br />Part Fibre Toxicol. 2024 Mar 11;21(1):15. (PMID: <searchLink fieldCode="PM" term="%2238468337%22">38468337)</searchLink><br />Ultrastruct Pathol. 2023 Nov 2;47(6):470-477. (PMID: <searchLink fieldCode="PM" term="%2237776320%22">37776320)</searchLink><br />Toxicol In Vitro. 2018 Feb;46:219-228. (PMID: <searchLink fieldCode="PM" term="%2228947239%22">28947239)</searchLink><br />Sci Rep. 2016 Dec 01;6:37842. (PMID: <searchLink fieldCode="PM" term="%2227905399%22">27905399)</searchLink><br />Proc Am Thorac Soc. 2008 Sep 15;5(7):763-6. (PMID: <searchLink fieldCode="PM" term="%2218757314%22">18757314)</searchLink><br />J Environ Monit. 2006 Jan;8(1):100-5. (PMID: <searchLink fieldCode="PM" term="%2216395465%22">16395465)</searchLink><br />Molecules. 2023 Feb 19;28(4):. (PMID: <searchLink fieldCode="PM" term="%2236838963%22">36838963)</searchLink><br />Toxicol In Vitro. 2013 Mar;27(2):721-30. (PMID: <searchLink fieldCode="PM" term="%2223220291%22">23220291)</searchLink><br />J Proteome Res. 2011 Feb 4;10(2):363-78. (PMID: <searchLink fieldCode="PM" term="%2221171652%22">21171652)</searchLink><br />Cytokine. 2022 Jun;154:155878. (PMID: <searchLink fieldCode="PM" term="%2235405483%22">35405483)</searchLink><br />Sci Rep. 2025 Nov 11;15(1):39488. (PMID: <searchLink fieldCode="PM" term="%2241219288%22">41219288)</searchLink><br />Int J Environ Res Public Health. 2021 Dec 13;18(24):. (PMID: <searchLink fieldCode="PM" term="%2234948756%22">34948756)</searchLink><br />J Clin Med. 2023 Mar 21;12(6):. (PMID: <searchLink fieldCode="PM" term="%2236983403%22">36983403)</searchLink><br />Toxicol Lett. 2011 Jan 15;200(1-2):109-16. (PMID: <searchLink fieldCode="PM" term="%2221087659%22">21087659)</searchLink><br />Eur J Pharm Sci. 2023 Nov 1;190:106567. (PMID: <searchLink fieldCode="PM" term="%2237633341%22">37633341)</searchLink><br />Cancer Res. 1985 Jun;45(6):2522-6. (PMID: <searchLink fieldCode="PM" term="%223986791%22">3986791)</searchLink><br />PLoS One. 2020 Jan 3;15(1):e0227174. (PMID: <searchLink fieldCode="PM" term="%2231900469%22">31900469)</searchLink><br />Toxicol Lett. 2011 Dec 15;207(3):278-85. (PMID: <searchLink fieldCode="PM" term="%2221983654%22">21983654)</searchLink><br />Eur J Pharm Biopharm. 2023 Mar;184:62-82. (PMID: <searchLink fieldCode="PM" term="%2236696943%22">36696943)</searchLink><br />Sci Rep. 2018 Jun 20;8(1):9398. (PMID: <searchLink fieldCode="PM" term="%2229925859%22">29925859)</searchLink><br />Life Sci. 2023 Dec 1;334:122208. (PMID: <searchLink fieldCode="PM" term="%2237884207%22">37884207)</searchLink><br />Pathol Res Pract. 2024 Feb;254:155122. (PMID: <searchLink fieldCode="PM" term="%2238246034%22">38246034)</searchLink><br />Toxicology. 2014 May 7;319:44-52. (PMID: <searchLink fieldCode="PM" term="%2224594012%22">24594012)</searchLink><br />Food Chem Toxicol. 2013 Dec;62:763-9. (PMID: <searchLink fieldCode="PM" term="%2224140967%22">24140967)</searchLink><br />Int J Environ Res Public Health. 2018 Jul 01;15(7):. (PMID: <searchLink fieldCode="PM" term="%2229966381%22">29966381)</searchLink><br />J Biochem Mol Toxicol. 2004;18(2):92-9. 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(PMID: <searchLink fieldCode="PM" term="%2212102499%22">12102499)</searchLink> – Name: GrantInfo Label: Grant Information Group: Grant Data: P30 ES029067 United States ES NIEHS NIH HHS; P42 ES027704 United States ES NIEHS NIH HHS – Name: SubjectMinor Label: Contributed Indexing Group: Data: <i>Keywords: </i>air–liquid interface culture; dose characterization; human lung epithelial cells; oxidative stress; submerged cell culture – Name: NumberCAS Label: Substance Nomenclature Group: ID Data: 0 (Volatile Organic Compounds)<br />0 (Air Pollutants) – Name: DateEntry Label: Entry Date(s) Group: Date Data: <i>Date Created: </i>20260820 <i>Date Completed: </i>20260909 <i>Latest Revision: </i>20260912 – Name: DateUpdate Label: Update Code Group: Date Data: 20260912 – Name: PubmedCentralID Label: PubMed Central ID Group: ID Data: PMC13557630 – Name: DOI Label: DOI Group: ID Data: 10.1093/toxsci/kfag110 – Name: AN Label: PMID Group: ID Data: 42623132 |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1093/toxsci/kfag110 Languages: – Code: eng Text: English Subjects: – SubjectFull: Oxidative Stress drug effects Type: general – SubjectFull: Inhalation Exposure adverse effects Type: general – SubjectFull: Humans Type: general – SubjectFull: Animals Type: general – SubjectFull: Volatile Organic Compounds toxicity Type: general – SubjectFull: Air Pollutants toxicity Type: general – SubjectFull: Toxicity Tests methods Type: general – SubjectFull: Lung drug effects Type: general – SubjectFull: Lung metabolism Type: general – SubjectFull: Lung pathology Type: general – SubjectFull: Epithelial Cells drug effects Type: general – SubjectFull: Epithelial Cells metabolism Type: general – SubjectFull: Epithelial Cells pathology Type: general Titles: – TitleFull: In vitro approaches to assess respiratory toxicity from volatile organic compounds: an in-depth review. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Lampe OCG – PersonEntity: Name: NameFull: Vitucci ECM – PersonEntity: Name: NameFull: Cannon CL – PersonEntity: Name: NameFull: Holland K – PersonEntity: Name: NameFull: Foster MJ – PersonEntity: Name: NameFull: Johnson NM IsPartOfRelationships: – BibEntity: Dates: – D: 02 M: 09 Text: 2026 Sep 02 Type: published Y: 2026 Identifiers: – Type: issn-electronic Value: 1096-0929 Numbering: – Type: volume Value: 209 – Type: issue Value: 9 Titles: – TitleFull: Toxicological sciences : an official journal of the Society of Toxicology Type: main |
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