title: Respiratory sensitization: advances in assessing the risk of respiratory inflammation and irritation.
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.
authors.affiliation: National Institute of Public Health & Environment, Bilthoven, The Netherlands. rob.vandebriel@rivm.nl
authors.forename: Rob
authors.initials: R
authors.lastname: Vandebriel
authors.forename: Conchita
authors.initials: C
authors.lastname: Callant Cransveld
authors.forename: Daan
authors.initials: D
authors.lastname: Crommelin
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Diamant
authors.forename: Berend
authors.initials: B
authors.lastname: Glazenburg
authors.forename: Guy
authors.initials: G
authors.lastname: Joos
authors.forename: Frieke
authors.initials: F
authors.lastname: Kuper
authors.forename: Andreas
authors.initials: A
authors.lastname: Natsch
authors.forename: Frans
authors.initials: F
authors.lastname: Nijkamp
authors.forename: Hub
authors.initials: H
authors.lastname: Noteborn
authors.forename: Raymond
authors.initials: R
authors.lastname: Pieters
authors.forename: David
authors.initials: D
authors.lastname: Roberts
authors.forename: Erwin
authors.initials: E
authors.lastname: Roggen
authors.forename: Emiel
authors.initials: E
authors.lastname: Rorije
authors.forename: Martin
authors.initials: M
authors.lastname: Seed
authors.forename: Katharina
authors.initials: K
authors.lastname: Sewald
authors.forename: Rosette
authors.initials: R
authors.lastname: van den Heuvel
authors.forename: Jacqueline
authors.initials: J
authors.lastname: van Engelen
authors.forename: Sandra
authors.initials: S
authors.lastname: Verstraelen
authors.forename: Henk
authors.initials: H
authors.lastname: van Loveren
mesh_terms: D000826:Animal Testing Alternatives; D015386:Hazardous Substances / Q000276:immunology*; D006801:Humans; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology; D012140:Respiratory Tract Diseases / Q000139:chemically induced*; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards*
chemical_list: D015386:Hazardous Substances