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NURA NAMs Spotlight: Advancing Respiratory Sensitization Research with ALIsens® In Vitro Model
Thursday, January 30, 2025, 10:00 AM - 11:00 AM EST
Category: Partner Webinar

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Thursday, January 30, 2025
10:00 am ET / 15:00 UTC

Featuring:
Sabina Burlă, MSC, Chief Scientific Officer at Invitrolize
Arno Gutleb, PhDFounder and Managing Director of Invitrolize

ABSTRACT
The development of in vitro models for the respiratory tract is crucial as an alternative to animal testing, addressing significant limitations in the predictive accuracy of animal models. Traditional animal models often fail to accurately replicate the anatomical and physiological characteristics of the human respiratory system, leading to challenges in hazard assessment [1]. Additionally, advancing NAMs aligns with the Replacement principle postulated by Russel and Burch, promoting ethical research practices while enhancing relevance and reliability of safety evaluation for human health. Specifically, filling the gaps of knowledge in the respiratory sensitization mechanism following the golden standard of the skin sensitization adverse outcome pathway (AOP) currently represents a research focus [2].
An in vitro model for the identification of respiratory sensitizers, ALIsens®, was developed at the Luxembourg Institute of Science and Technology (LIST) [3]. ALIsens®, a complex three-dimensional (3D) model, is built using human cell lines: alveolar type II epithelial (A549), endothelial (EA.hy926) and monocytes (THP-1). The cellular architecture within the test system favors the development of a tissue-like microenvironment by cell-to-cell direct communication and indirectly through the secreted messenger molecules. Additionally, it facilitates the exposure of respiratory sensitizers in a more realistic approach, at the air-liquid-interface (ALI). The model has been shown to correctly identify respiratory sensitizers belonging to acid anhydrides chemical class [3] and differentiate them from skin sensitizers and non-sensitizers based on the increased expression of markers of the surface of dendritic-like cells, thymic stromal lymphopoietin receptor (TSLPr), cluster or differentiation (CD)86 and CD54 [4], the profile of secreted messenger molecules (cytokines and chemokines) and gene expression [3].
To establish accurate sensitizer classification, a threshold for TSLPr cell surface marker must be defined. The model’s accuracy, sensitivity and specificity of the model will be evaluated within a broader context, utilizing data from exposures to respiratory and skin sensitizers as well as non-sensitizers. This comprehensive approach aims to enhance the predictive power and reliability of ALIsens® for distinguishing respiratory from skin sensitizers and from non-sensitizers across different exposure types.
[1] Stucki, A.O. Differences in The Anatomy and Physiology of the Human and Rat Respiratory Tracts and Impact on Toxicological Assessments. Regulatory Toxicology and Pharmacology. 2024. DOI: 10.1016/j.yrtph.2024.105648
[2] Hargitai, R. Chemical Respiratory Sensitization—Current Status of Mechanistic Understanding, Knowledge Gaps and Possible Identification Methods of Sensitizers. Frontiers in Toxicology. 2024. DOI: 10.3389/ftox.2024.1331803
[3] Chary, A. An In Vitro Coculture System for the Detection of Sensitization Following Aerosol Exposure. ALTEX. 2019. DOI: 10.14573/altex.1901241
[4] Burla, S. Responses of an In Vitro Coculture Alveolar Model for the Prediction of Respiratory Sensitizers (ALIsens®) Following Exposure to Skin Sensitizers and Non-Sensitizers. Toxics. 2025. DOI: 10.3390/toxics13010029.

ABOUT THE PRESENTERS
Sabina Burlă is a scientist specializing in toxicology and in vitro modelling. She earned her master’s degrees in Pharmacy and Drug and Environmental Toxicology from “Iuliu Hatieganu” University of Medicine and Pharmacy in Cluj-Napoca, Romania. Her activities in the field of inhalation toxicology focused in developing innovative 3D alveolar in vitro models to predict respiratory sensitization and irritation, contributing significantly to reducing animal testing in research. Her work has been recognized with awards from the European Society of Toxicology In Vitro (ESTIV) and the Society of Toxicology (SOT). Currently, she serves as the Chief Scientific Officer at Invitrolize, a spin-off from the Luxembourg Institute of Science and Technology (LIST), where she continues to advance in vitro methodologies for respiratory toxicology. Sabina actively participates in international conferences and workshops, sharing her expertise on new approach methodologies in toxicology.

Dr. Arno Gutleb graduated from the University of Veterinary Medicine Vienna, Austria and holds a PhD in Environmental Sciences with specialization in toxicology from Wageningen University, The Netherlands and is a European Registered Toxicologist (ERT). He is Distinguished Professor at the University Iuliu Hatieganu, Cluj, Romania and Visiting Professor at the Universidad Andrés Bello, Santiago de Chile. He is Founder and Managing Director of INVITROLIZE, a company focusing on in vitro methods to identify respiratory sensitizers.

For your convenience, the materials and resources from this webinar will also be posted to https://PCRM.org/NAMSpotlight.

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