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Animal models to test respiratory allergy of low molecular weight chemicals: A guidance

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Author: Arts, J.H.E. · Kuper, C.F.
Type:article
Date:2007
Institution: TNO Kwaliteit van Leven
Source:Methods, 1, 41, 61-71
Identifier: 239784
doi: doi:10.1016/j.ymeth.2006.07.005
Keywords: Health · Toxicology and Applied Pharmacology · Animal model · Challenge · LMW chemical · Respiratory allergy · Sensitisation · Test method · allergen · chemical compound · allergic asthma · animal experiment · animal model · article · controlled study · dose response · maximum allowable concentration · mouse · nonhuman · priority journal · rat · respiratory tract allergy · risk assessment · sensitivity analysis · sensitization · Allergens · Animals · Asthma · Disease Models, Animal · Guidelines · Hypersensitivity · Irritants · Molecular Weight · Toxicity Tests · Animalia

Abstract

At present, there are no widely applied or fully validated test methods to identify respiratory LMW allergens, i.e. compounds that are considered capable of inducing allergic asthma. Most tests have been investigated using strong respiratory allergens. Moreover, they are meant to detect the potential of a chemical to induce respiratory sensitisation at relatively high doses. Consequently, the sensitivity of the tests is not well-known, and they do not provide information on low doses such as generally found in occupational situations, and on threshold levels to be used in risk assessment. In addition, the various test methods use different application routes, i.e. intradermal, topical or inhalation exposure, and different parameters. Therefore standardised and validated dose-response test methods are urgently required in order to be able to identify respiratory allergens and to recommend safe exposure levels for consumers and workers. In the present paper, methods or testing strategies are described to detect respiratory sensitisation and/or allergy. Overall, assays that utilize only an induction phase may serve as indicators of respiratory sensitisation potential whereas assays that use both an induction and an elicitation or challenge phase may provide information on potency and presence of thresholds. The dermal route as sensitisation route has the advantage of the respiratory tract not being exposed to the allergen prior to challenge which facilitates the distinction between irritant and allergic effects. © 2006 Elsevier Inc. All rights reserved.