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Respiratory sensitization : Advances in assessing the risk of respiratory inflammation and irritation

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Author: Vandebriel, R. · Callant Cransveld, C. · Crommelin, D. · Diamant, Z. · Glazenburg, B. · Joos, G. · Kuper, F. · Natsch, A. · Nijkamp, F. · Noteborn, H. · Pieters, R. · Roberts, D. · Roggen, E. · Rorije, E. · Seed, M. · Sewald, K. · Heuvel, R. van den · Engelen, J. van · Verstraelen, S. · Loveren, H. van
Source:Toxicology in Vitro, 7, 25, 1251-1258
Identifier: 460484
doi: doi:10.1016/j.tiv.2011.04.027
Keywords: Toxicology · ASAT · Asthma · In vitro · In vivo · Integrated testing · QSAR · Respiratory tract · Rhinitis · Risk assessment · Sensitization · contact allergen · immunoglobulin E · airway remodeling · animal testing alternative · biosafety · bronchus hyperreactivity · cell assay · cellular immunity · dendritic cell · disease predisposition · functional genomics · human · immunopathology · immunoreactivity · in vitro study · mathematical model · mucosal immunity · nonhuman · occupational asthma · predictive value · process development · process model · quantitative analysis · quantitative structure activity relation · reaction analysis · respiratory sensitization · respiratory tract inflammation · respiratory tract injury · review · risk assessment · risk factor · sensitization · Animal Testing Alternatives · Hazardous Substances · Humans · Respiratory Hypersensitivity · Respiratory Tract Diseases · Toxicity Tests · Animalia · Healthy for Life · Healthy Living · Life · QS - Quality & Safety · EELS - Earth, Environmental and Life Sciences


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. © 2011 Elsevier Ltd.