title: Developing a framework for assessing chemical respiratory sensitization: A workshop report.
abstract: Respiratory tract sensitization can have significant acute and chronic health implications. While induction of respiratory sensitization is widely recognized for some chemicals, validated standard methods or frameworks for identifying and characterizing the hazard are not available. A workshop on assessment of respiratory sensitization was held to discuss the current state of science for identification and characterization of respiratory sensitizer hazard, identify information facilitating development of validated standard methods and frameworks, and consider the regulatory and practical risk management needs. Participants agreed on a predominant Th2 immunological mechanism and several steps in respiratory sensitization. Some overlapping cellular events in respiratory and skin sensitization are well understood, but full mechanism(s) remain unavailable. Progress on non-animal approaches to skin sensitization testing, ranging from in vitro systems, -omics, in silico profiling, and structural profiling were acknowledged. Addressing both induction and elicitation phases remains challenging. Participants identified lack of a unifying dose metric as increasing the difficulty of interpreting dosimetry across exposures. A number of research needs were identified, including an agreed list of respiratory sensitizers and other asthmagens, distinguishing between adverse effects from immune-mediated versus non-immunological mechanisms. A number of themes emerged from the discussion regarding future testing strategies, particularly the need for a tiered framework respiratory sensitizer assessment. These workshop present a basis for moving towards a weight-of-evidence assessment.
authors.affiliation: ExxonMobil Biomedical Sciences, Inc., Annandale, NJ, USA. Electronic address: colin.m.north@exxonmobil.com.
authors.forename: Colin M
authors.initials: CM
authors.lastname: North
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Janine
authors.initials: J
authors.lastname: Ezendam
authors.affiliation: Dow Chemical Company - Toxicology and Environmental Research and Consulting, Midland, MI, USA.
authors.forename: Jon A
authors.initials: JA
authors.lastname: Hotchkiss
authors.affiliation: GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Maier
authors.affiliation: Kagoshima University, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Aoyama
authors.affiliation: Liverpool John Moores University, Liverpool, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Enoch
authors.affiliation: Syngenta, Greensboro, NC, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Goetz
authors.affiliation: Hunstman LLC, The Woodlands, TX, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Graham
authors.affiliation: Faculty of Life Sciences, University of Manchester, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
authors.affiliation: European Chemicals Agency, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Karjalainen
authors.affiliation: Bayer Pharma, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Pauluhn
authors.affiliation: 3Rs Management and Consulting ApS, Lyngby, Denmark.
authors.forename: Erwin L
authors.initials: EL
authors.lastname: Roggen
authors.affiliation: ICF International, USA.
authors.forename: MaryJane
authors.initials: M
authors.lastname: Selgrade
authors.affiliation: University of Toronto, Toronto, Ontario, Canada.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Tarlo
authors.affiliation: ILSI - Health and Environmental Sciences Institute, Washington, DC, USA.
authors.forename: Connie L
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D059366:Asthma, Occupational / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D017449:Dermatitis, Allergic Contact / Q000209:etiology; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D012137:Respiratory System / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D018570:Risk Assessment; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D018675:Toxicity Tests / Q000379:methods*; D043922:Toxicogenetics
keywords: Framework; Hazard identification; Inhalation; In vitro; In vivo; Respiratory sensitization; Sensitization; Skin; Tiered approach; Workshop report