P25-19 Unravelling Respiratory Toxicity of PFAS: One Cell at a Time [* Cross-Reference *]

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Emma Arnesdotter; Luca Mannino; Patricia A. Weber; Antonio Federico; Alessia Rocchi; Chiara Leo; Arno C. Gutleb; Dario Greco; Tommaso Serchi, 2026, "P25-19 Unravelling Respiratory Toxicity of PFAS: One Cell at a Time [* Cross-Reference *]", https://lore.list.lu/citation?persistentId=perma:LIST.CCEVVS, LIST Open Repository, V1

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Description	Per- and polyfluoroalkyl substances (PFAS) represent a critical group of persistent environmental contaminants, widely recognised for their bioaccumulation potential and adverse effects on human health. Their interaction with the respiratory system, particularly through inhalation exposure, remains understudied. Here, we aim to elucidate the respiratory toxicity and cellular responses induced by selected PFAS compounds using ALIsens, an advanced human-relevant in vitro model. The ALIsens model is a sophisticated 3-dimensional co-culture model cultivated at the air-liquid interface, combining epithelial cells (A549), PMA-differentiated macrophages (THP-1), endothelial cells (EA.hy926), and naïve THP-1 cells. This configuration accurately replicates key anatomical and functional features of the human respiratory tract, facilitating physiologically relevant exposure scenarios. We exposed the ALIsens model to seven environmentally relevant PFAS. Single-cell transcriptomics (scRNA-seq) was applied to dissect cell-type specific molecular responses and identify sensitive biomarkers of PFAS-induced cellular stress, inflammation, and barrier dysfunction. Additional functional endpoints were assessed to link transcriptional changes with altered tissue-level outcomes. Initial results are expected to shed light on critical mechanistic pathways influenced by PFAS exposure in human respiratory tissues, including immune modulation and inflammatory responses. Ultimately, this research will enhance our understanding of PFAS toxicity at the respiratory interface, guiding the development of predictive assays and regulatory strategies to safeguard human health. This work highlights the importance of advanced in vitro methodologies, such as ALIsens, as valuable tools within next-generation toxicological assessments, aligning with the ongoing transition towards human-relevant and animal-free research models. The results are expected to inform on potential apical effects that can be measured in high throughput assays, and so contributing to a testing toolbox to improve and address the hazard of PFAS exposure to human health and ultimately, facilitate read-across actions between legacy and poor-data congeners. (2025-09-01) *This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1016/j.toxlet.2025.07.750 for the original and latest version of the publication* (2026-07-01)
Subject	Medicine, Health and Life Sciences
Keyword	Toxicity, Adverse Outcome Pathway, Respiratory system, Transcriptome, In vitro, In vivo, Mechanism (biology), In vitro toxicology
License/Data Use Agreement	Custom Dataset Terms


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Persistent Identifier	perma:LIST.CCEVVS
Publication Date	2026-07-06
Title	P25-19 Unravelling Respiratory Toxicity of PFAS: One Cell at a Time [* Cross-Reference *]
Other Identifier	https://doi.org/10.1016/j.toxlet.2025.07.750 OpenAlex ID: https://openalex.org/W4414076589
Author	Emma Arnesdotter (Luxembourg Institute of Science and Technology) - ORCID: https://orcid.org/0000-0002-5891-5479 Luca Mannino (Tampere University of Applied Sciences, Tampere University) Patricia A. Weber (Luxembourg Institute of Science and Technology) - ORCID: https://orcid.org/0000-0003-4562-1276 Antonio Federico (Tampere University of Applied Sciences, Tampere University) - ORCID: https://orcid.org/0000-0003-2554-9879 Alessia Rocchi (Polo d’Innovazione di Genomica) Chiara Leo (Polo d’Innovazione di Genomica) - ORCID: https://orcid.org/0000-0003-0510-2535 Arno C. Gutleb (Luxembourg Institute of Science and Technology) - ORCID: https://orcid.org/0000-0001-9725-9112 Dario Greco (University of Helsinki, Tampere University of Applied Sciences, Tampere University) - ORCID: https://orcid.org/0000-0001-9195-9003 Tommaso Serchi (Luxembourg Institute of Science and Technology) - ORCID: https://orcid.org/0000-0003-2386-3514
Point of Contact	Use email button above to contact. LIST QDKM (LIST)
Description	Per- and polyfluoroalkyl substances (PFAS) represent a critical group of persistent environmental contaminants, widely recognised for their bioaccumulation potential and adverse effects on human health. Their interaction with the respiratory system, particularly through inhalation exposure, remains understudied. Here, we aim to elucidate the respiratory toxicity and cellular responses induced by selected PFAS compounds using ALIsens, an advanced human-relevant in vitro model. The ALIsens model is a sophisticated 3-dimensional co-culture model cultivated at the air-liquid interface, combining epithelial cells (A549), PMA-differentiated macrophages (THP-1), endothelial cells (EA.hy926), and naïve THP-1 cells. This configuration accurately replicates key anatomical and functional features of the human respiratory tract, facilitating physiologically relevant exposure scenarios. We exposed the ALIsens model to seven environmentally relevant PFAS. Single-cell transcriptomics (scRNA-seq) was applied to dissect cell-type specific molecular responses and identify sensitive biomarkers of PFAS-induced cellular stress, inflammation, and barrier dysfunction. Additional functional endpoints were assessed to link transcriptional changes with altered tissue-level outcomes. Initial results are expected to shed light on critical mechanistic pathways influenced by PFAS exposure in human respiratory tissues, including immune modulation and inflammatory responses. Ultimately, this research will enhance our understanding of PFAS toxicity at the respiratory interface, guiding the development of predictive assays and regulatory strategies to safeguard human health. This work highlights the importance of advanced in vitro methodologies, such as ALIsens, as valuable tools within next-generation toxicological assessments, aligning with the ongoing transition towards human-relevant and animal-free research models. The results are expected to inform on potential apical effects that can be measured in high throughput assays, and so contributing to a testing toolbox to improve and address the hazard of PFAS exposure to human health and ultimately, facilitate read-across actions between legacy and poor-data congeners. (2025-09-01) *This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1016/j.toxlet.2025.07.750 for the original and latest version of the publication* (2026-07-01)
Subject	Medicine, Health and Life Sciences
Keyword	Toxicity Adverse Outcome Pathway Respiratory system Transcriptome In vitro In vivo Mechanism (biology) In vitro toxicology
Topic Classification	Radiopharmaceutical Chemistry and Applications Medical Imaging Techniques and Applications
Deposit Date	2025-09-01
Data Type	Article
Data Source	Toxicology Letters

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