Responses of an <i>In Vitro</i> Coculture Alveolar Model for the Prediction of Respiratory Sensitizers (ALIsens<sup>®</sup>) Following Exposure to Skin Sensitizers and Non-Sensitizers
In recent years, a global increase in allergy incidence following chemical exposure has been observed. While the process of skin sensitization is well characterized through the adverse outcome pathway (AOP) framework, the immunological mechanisms underlying respiratory sensitization remain less well...
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MDPI AG
2024-12-01
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| author | Sabina Burla Aline Chary Tommaso Serchi Sébastien Cambier Kristie Sullivan Elizabeth Baker Nikaeta Sadekar Arno C. Gutleb |
| author_facet | Sabina Burla Aline Chary Tommaso Serchi Sébastien Cambier Kristie Sullivan Elizabeth Baker Nikaeta Sadekar Arno C. Gutleb |
| author_sort | Sabina Burla |
| collection | DOAJ |
| description | In recent years, a global increase in allergy incidence following chemical exposure has been observed. While the process of skin sensitization is well characterized through the adverse outcome pathway (AOP) framework, the immunological mechanisms underlying respiratory sensitization remain less well understood. Respiratory sensitizers are classified as substances of very high concern (SVHC) under the European Union (EU) regulation for the registration, evaluation, authorization and restriction of chemicals (REACH), emphasizing the importance of evaluating respiratory tract sensitization as a critical hazard. However, the existing new approach methodologies (NAMs) for the identification of skin sensitizers lack the capacity to differentiate between skin and respiratory sensitizers. Thus, it is imperative to develop physiologically relevant test systems specifically tailored to assess respiratory sensitizers. This study aimed to evaluate the efficacy of ALIsens<sup>®</sup>, a three-dimensional (3D) <i>in vitro</i> alveolar model designed for the identification of respiratory sensitizers and to determine its ability to correctly identify sensitizers. In this study, we used a range of skin sensitizers and non-sensitizers to define the optimal exposure dose, identify biomarkers, and establish tentative thresholds for correct sensitizer classification. The results demonstrate that ALIsens<sup>®</sup> is a promising <i>in vitro</i> complex model that could successfully discriminate respiratory sensitizers from skin sensitizers and non-sensitizers. Furthermore, the thymic stromal lymphopoietin receptor (TSLPr) cell surface marker was confirmed as a reliable biomarker for predicting respiratory sensitization hazards. |
| format | Article |
| id | doaj-art-815220e3105b4617a7170297b92e9ce6 |
| institution | Kabale University |
| issn | 2305-6304 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj-art-815220e3105b4617a7170297b92e9ce62025-01-24T13:50:59ZengMDPI AGToxics2305-63042024-12-011312910.3390/toxics13010029Responses of an <i>In Vitro</i> Coculture Alveolar Model for the Prediction of Respiratory Sensitizers (ALIsens<sup>®</sup>) Following Exposure to Skin Sensitizers and Non-SensitizersSabina Burla0Aline Chary1Tommaso Serchi2Sébastien Cambier3Kristie Sullivan4Elizabeth Baker5Nikaeta Sadekar6Arno C. Gutleb7Luxembourg Institute of Science and Technology (LIST), 4422 Belvaux, LuxembourgLuxembourg Institute of Science and Technology (LIST), 4422 Belvaux, LuxembourgLuxembourg Institute of Science and Technology (LIST), 4422 Belvaux, LuxembourgLuxembourg Institute of Science and Technology (LIST), 4422 Belvaux, LuxembourgPhysicians Committee for Responsible Medicine (PCRM), Washington, DC 20016, USAPhysicians Committee for Responsible Medicine (PCRM), Washington, DC 20016, USAResearch Institute for Fragrance Materials (RIFM), Woodcliff Lake, NJ 07430, USALuxembourg Institute of Science and Technology (LIST), 4422 Belvaux, LuxembourgIn recent years, a global increase in allergy incidence following chemical exposure has been observed. While the process of skin sensitization is well characterized through the adverse outcome pathway (AOP) framework, the immunological mechanisms underlying respiratory sensitization remain less well understood. Respiratory sensitizers are classified as substances of very high concern (SVHC) under the European Union (EU) regulation for the registration, evaluation, authorization and restriction of chemicals (REACH), emphasizing the importance of evaluating respiratory tract sensitization as a critical hazard. However, the existing new approach methodologies (NAMs) for the identification of skin sensitizers lack the capacity to differentiate between skin and respiratory sensitizers. Thus, it is imperative to develop physiologically relevant test systems specifically tailored to assess respiratory sensitizers. This study aimed to evaluate the efficacy of ALIsens<sup>®</sup>, a three-dimensional (3D) <i>in vitro</i> alveolar model designed for the identification of respiratory sensitizers and to determine its ability to correctly identify sensitizers. In this study, we used a range of skin sensitizers and non-sensitizers to define the optimal exposure dose, identify biomarkers, and establish tentative thresholds for correct sensitizer classification. The results demonstrate that ALIsens<sup>®</sup> is a promising <i>in vitro</i> complex model that could successfully discriminate respiratory sensitizers from skin sensitizers and non-sensitizers. Furthermore, the thymic stromal lymphopoietin receptor (TSLPr) cell surface marker was confirmed as a reliable biomarker for predicting respiratory sensitization hazards.https://www.mdpi.com/2305-6304/13/1/29chemical allergynew approach methodologiesrespiratory sensitizationair-liquid-interface exposuredendritic cell activationcell surface markers |
| spellingShingle | Sabina Burla Aline Chary Tommaso Serchi Sébastien Cambier Kristie Sullivan Elizabeth Baker Nikaeta Sadekar Arno C. Gutleb Responses of an <i>In Vitro</i> Coculture Alveolar Model for the Prediction of Respiratory Sensitizers (ALIsens<sup>®</sup>) Following Exposure to Skin Sensitizers and Non-Sensitizers Toxics chemical allergy new approach methodologies respiratory sensitization air-liquid-interface exposure dendritic cell activation cell surface markers |
| title | Responses of an <i>In Vitro</i> Coculture Alveolar Model for the Prediction of Respiratory Sensitizers (ALIsens<sup>®</sup>) Following Exposure to Skin Sensitizers and Non-Sensitizers |
| title_full | Responses of an <i>In Vitro</i> Coculture Alveolar Model for the Prediction of Respiratory Sensitizers (ALIsens<sup>®</sup>) Following Exposure to Skin Sensitizers and Non-Sensitizers |
| title_fullStr | Responses of an <i>In Vitro</i> Coculture Alveolar Model for the Prediction of Respiratory Sensitizers (ALIsens<sup>®</sup>) Following Exposure to Skin Sensitizers and Non-Sensitizers |
| title_full_unstemmed | Responses of an <i>In Vitro</i> Coculture Alveolar Model for the Prediction of Respiratory Sensitizers (ALIsens<sup>®</sup>) Following Exposure to Skin Sensitizers and Non-Sensitizers |
| title_short | Responses of an <i>In Vitro</i> Coculture Alveolar Model for the Prediction of Respiratory Sensitizers (ALIsens<sup>®</sup>) Following Exposure to Skin Sensitizers and Non-Sensitizers |
| title_sort | responses of an i in vitro i coculture alveolar model for the prediction of respiratory sensitizers alisens sup r sup following exposure to skin sensitizers and non sensitizers |
| topic | chemical allergy new approach methodologies respiratory sensitization air-liquid-interface exposure dendritic cell activation cell surface markers |
| url | https://www.mdpi.com/2305-6304/13/1/29 |
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