Chemical Respiratory Allergy: Opportunities for Hazard Identification and Characterisation

Kimber, Ian; Agius, Raymond; Basketter, David A.; Corsini, Emanuela; Cullinan, Paul; Dearman, Rebecca J.; Giménez‐Arnau, Elena; Greenwell, Leona L.; Hartung, Thomas; Kuper, Frieke; Maestrelli, Piero; Roggen, Erwin L.; Rovida, Costanza

doi:10.1177/026119290703500212

Cited by 64 publications

(53 citation statements)

References 180 publications

(193 reference statements)

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“…The list of methods and approaches provided is not, and is not intended to be, comprehensive or exhaustive, and for a more detailed consideration of the models that have been -or are beingdeveloped there are available [ 1 5 4 _ T D $ D I F F ] numerous relevant review articles (Holsapple et al, 2006;Kimber et al, 2007;Boverhof et al, 2008;Vandebriel et al, 2011;Rovida et al, 2013).…”

Section: Proposed Approaches For Hazard Identification and Characterimentioning

confidence: 99%

“…Nevertheless, there is a variety of cell/tissue culture methods that have been proposed (Kimber et al, 2007;Boverhof et al, 2008). One development is based on the Direct Peptide Reactivity Assay that was described initially as a method for the identification of contact allergens in which the interaction of chemicals with model peptides is measured (Gerberick et al, 2004).…”

Section: In Vitro Test Systemsmentioning

confidence: 99%

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Thresholds in chemical respiratory sensitisation

et al. 2015

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There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the acquisition of sensitisation to chemical respiratory allergens is a dose-related phenomenon, and that thresholds exist, it is frequently difficult to define accurate numerical values for threshold exposure levels. Nevertheless, based on occupational exposure data it may sometimes be possible to derive levels of exposure in the workplace, which are safe. An additional observation is the lack currently of suitable experimental methods for both routine hazard characterisation and the measurement of thresholds, and that such methods are still some way off. Given the current trajectory of toxicology, and the move towards the use of non-animal in vitro and/or in silico) methods, there is a need to consider the development of alternative approaches for the identification and characterisation of respiratory sensitisation hazards, and for risk assessment.

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Section: Proposed Approaches For Hazard Identification and Characterimentioning

confidence: 99%

Section: In Vitro Test Systemsmentioning

confidence: 99%

Thresholds in chemical respiratory sensitisation

et al. 2015

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“…Although there is evidence that chemical respiratory allergens differ from contact allergens in the quality of immune response-that is, the ability to provoke the preferential development of T H 2-type immune responses-the physicochemical properties of chemical allergens that dictate the type of sensitization they will cause remain largely unknown. 12,13 Intensity of exposure…”

Section: Role Of Exposure In Pathophysiologic Mechanisms Characteristmentioning

confidence: 99%

Mechanisms of occupational asthma

Maestrelli

Boschetto

Fabbri

et al. 2009

Journal of Allergy and Clinical Immunology

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“…There are available elsewhere reviews, including some recent reviews, of sensitisation of the respiratory tract by chemicals and occupational asthma, and of issues relating to toxicological evaluation (Holsapple et al, 2006;Kimber and Wilks, 1995;Kimber and Dearman, 2005;Kimber et al, 2007;Isola et al, 2008;Roggen et al, 2008;Boverhof et al, 2008). The key issue is that, despite considerable effort, we still do not have available a widely accepted or formally validated method for the identification and characterisation of chemical respiratory allergens.…”

Section: Sensitisation Of the Respiratory Tractmentioning

confidence: 99%

“…Of particular importance have been attempts to move away from traditional inhalation models in rats and guinea pigs that were often technically laborious and costly, and to embrace instead approaches based on the immunobiology of sensitisation Boverhof et al, 2008). There is interest also in establishing SAR relationships, and in exploiting for the purposes of respiratory sensitisation hazard identification progress that is being made in the design of in vitro approaches to skin sensitisation testing (Holsapple et al, 2006;Kimber et al, 2007). There is, however, some considerable way still to go.…”

Section: Sensitisation Of the Respiratory Tractmentioning

confidence: 99%