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REVIEW article

Front. Toxicol.
Sec. Immunotoxicology
Volume 6 - 2024 | doi: 10.3389/ftox.2024.1331803
This article is part of the Research Topic European Partnership on the Assessment of Risks from Chemicals (PARC): Focus on New Approach Methodologies (NAMs) in Risk Assessment View all 9 articles

Chemical respiratory sensitizationcurrent status of mechanistic understanding, knowledge gaps and possible identification methods of sensitizers

Provisionally accepted
Rita Hargitai Rita Hargitai 1*Lucia Parráková Lucia Parráková 2Tünde Szatmári Tünde Szatmári 1*Pablo Monfort-Lanzas Pablo Monfort-Lanzas 2*Valentina Galbiati Valentina Galbiati 3Karine Audouze Karine Audouze 4Florence Jornod Florence Jornod 4Yvonne Staal Yvonne Staal 5Sabina Burla Sabina Burla 6Aline Chary Aline Chary 6Arno Gutleb Arno Gutleb 6Katalin Lumniczky Katalin Lumniczky 1*Rob Vandebriel Rob Vandebriel 5*Johanna M. Gostner Johanna M. Gostner 2*
  • 1 Unit of Radiation Medicine, Department of Radiobiology and Radiohygiene, National Centre for Public Health and Pharmacy (NCPHP), Budapest,, Hungary
  • 2 Biochemical Immunotoxicology Group, Institute of Medical Biochemistry, Medical University of Innsbruck (MUI), Innsbruck, Tyrol, Austria
  • 3 Laboratory of Toxicology, Department of Pharmacological and Biomolecular Sciences ‘Rodolfo Paoletti', Università degli Studi di Milano (UNIMI), Milano, Italy
  • 4 Université Paris Cité, Inserm UMR-S 1124, 45 rue des Saints-Pères- 75006, Paris, France
  • 5 Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
  • 6 Department of Environmental Research and Innovation, Luxembourg Institute of Science and Technology (LIST), Belval, Luxembourg

The final, formatted version of the article will be published soon.

    Respiratory sensitization is a complex immunological process eventually leading to hypersensitivity following re-exposure to the chemical. A frequent consequence is occupational asthma, which may occur after long latency periods. Although chemical-induced respiratory hypersensitivity has been known for decades, there are currently no comprehensive and validated approaches available for the prospective identification of chemicals that induce respiratory sensitization, while the expectations of new approach methodologies (NAMs) are high. A great hope is that due to a better understanding of the molecular key events, new methods can be developed now. However, this is a big challenge due to the different chemical classes to which respiratory sensitizers belong, as well as because of the complexity of the response and the late manifestation of symptoms. In this review article, the current information on respiratory sensitization related processes is summarized by introducing it in the available adverse outcome pathway (AOP) concept. Potentially useful models for prediction are discussed. Knowledge gaps and gaps of regulatory concern are identified.Literature-identified respiratory sensitizers (

    Keywords: Adverse outcome pathway (AOP), chemical respiratory allergy, chemical sensitizer, Chemical-induced hypersensitivity, Key event, New approach methodology (NAM), occupational, Respiratory sensitization

    Received: 01 Nov 2023; Accepted: 27 May 2024.

    Copyright: © 2024 Hargitai, Parráková, Szatmári, Monfort-Lanzas, Galbiati, Audouze, Jornod, Staal, Burla, Chary, Gutleb, Lumniczky, Vandebriel and Gostner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Rita Hargitai, Unit of Radiation Medicine, Department of Radiobiology and Radiohygiene, National Centre for Public Health and Pharmacy (NCPHP), Budapest,, Hungary
    Tünde Szatmári, Unit of Radiation Medicine, Department of Radiobiology and Radiohygiene, National Centre for Public Health and Pharmacy (NCPHP), Budapest,, Hungary
    Pablo Monfort-Lanzas, Biochemical Immunotoxicology Group, Institute of Medical Biochemistry, Medical University of Innsbruck (MUI), Innsbruck, Tyrol, Austria
    Katalin Lumniczky, Unit of Radiation Medicine, Department of Radiobiology and Radiohygiene, National Centre for Public Health and Pharmacy (NCPHP), Budapest,, Hungary
    Rob Vandebriel, Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
    Johanna M. Gostner, Biochemical Immunotoxicology Group, Institute of Medical Biochemistry, Medical University of Innsbruck (MUI), Innsbruck, Tyrol, Austria

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.