Respiratory sensitization: Advances in assessing the risk of respiratory inflammation and irritation |
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| Authors: | Rob Vandebriel Conchita Callant Cransveld Daan Crommelin Zuzana Diamant Berend Glazenburg Guy Joos Frieke Kuper Andreas Natsch Frans Nijkamp Hub Noteborn Raymond Pieters David Roberts Erwin Roggen Emiel Rorije Martin Seed Katharina Sewald Rosette van den Heuvel Jacqueline van Engelen Sandra Verstraelen Henk van Loveren |
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| Affiliation: | aNational Institute of Public Health & the Environment, Bilthoven, The Netherlands;bSenterNovem, The Hague, The Netherlands;cTop Institute Pharma, Leiden, The Netherlands;dCenter for Human Drug Research, Leiden, The Netherlands;eBronovo Hospital, The Hague, The Netherlands;fGhent University, Ghent, Belgium;gTNO, Zeist, The Netherlands;hGivaudan, Duebendorf, Switzerland;iUtrecht University, Utrecht, The Netherlands;jFood and Consumer Product Safety Authority, The Hague, The Netherlands;kLiverpool University, Liverpool, United Kingdom;lNovozymes, Bagsvaerd, Denmark;mManchester University, Manchester, United Kingdom;nFraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany;oVITO, Mol, Belgium |
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| Abstract: | Respiratory sensitization provides a case study for a new approach to chemical safety evaluation, as the prevalence of respiratory sensitization has increased considerably over the last decades, but animal and/or human experimental/predictive models are not currently available. Therefore, the goal of a working group was to design a road map to develop an ASAT approach for respiratory sensitisers. This approach should aim at (i) creating a database on respiratory functional biology and toxicology, (ii) applying data analyses to understand the multi-dimensional sensitization response, and how this predisposes to respiratory inflammation and irritation, and (iii) building a systems model out of these analyses, adding pharmacokinetic–pharmacodynamic modeling to predict respiratory responses to low levels of sensitisers. To this end, the best way forward would be to follow an integrated testing approach. Experimental research should be targeted to (i) QSAR-type approaches to relate potential as a respiratory sensitizer to its chemical structure, (ii) in vitro models and (iii) in vitro–in vivo extrapolation/validation. |
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| Keywords: | ASAT Respiratory tract Sensitization Rhinitis Asthma Integrated testing Risk assessment QSAR In vitro In vivo |
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