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Oxazolone (OXA) is a respiratory allergen in Brown Norway rats

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Author: Kuper, C.F. · Radonjic, M. · Triel, J. van · Stierum, R. · Groot, R.J. de · Arts, J.H.E.
Type:article
Date:2011
Source:Toxicology, 1, 290, 59-68
Identifier: 441350
doi: doi:10.1016/j.tox.2011.08.017
Keywords: Toxicology · 4-Ethoxymethylene-2-phenyl-2-oxazoline-5-one · Allergic laryngitis · Gene expression · GZMB · Neutrophils · SELP · Life Triskelion BV · QS - Quality & Safety TAP - Toxicology and Applied Pharmacology · EELS - Earth, Environmental and Life Sciences TNO Bedrijven

Abstract

Oxazolone (OXA) is a potent contact allergen in man, and it is used as a model Th1-allergen to test (Q)SAR's and screening assays for allergenic potential of chemicals. However, it elevates serum IgE levels and Thelper2 cytokines at relatively low doses in test animals, suggesting that it has also respiratory allergenic potential. The lack of human data on respiratory allergenic potential of OXA may be due to lack of significant inhalation exposure. Here, female Brown Norway rats (BN) were sensitized by two or five dermal applications of OXA at the same total dose of 3.75mg. Controls received vehicle. All animals were challenged by inhalation to 45mg/m3 OXA on day 21 and necropsy was performed on day 22. All sensitized animals had increased serum IgE. OXA challenge decreased breathing frequency, and induced apnoeic breathing in the sensitized animals - a hallmark of respiratory allergy in our model. An exudative, granulocytic inflammation was observed primarily in the larynx of the sensitized and challenged rats. Microarray analysis of lung tissue, sampled 24h after challenge, revealed upregulation of several genes and activation of Gene Ontology (GO) pathways, which resembled more closely those found previously in lung tissue of rats sensitized and challenged by the respiratory allergen trimellitic anhydride than by the contact allergen dinitrochlorobenzene. The results indicate that the contact allergen OXA can also be a respiratory allergen, provided that it is inhaled. Its use as a model contact sensitizer must be reconsidered. © 2011 Elsevier Ireland Ltd.