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Pre-exposure to sulfur dioxide attenuates most allergic reactions upon trimellitic anhydride challenge in sensitized Brown Norway rats

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Author: Arts, J.H.E. · Jacobs, E.J. · Kuper, C.F.
Institution: TNO Kwaliteit van Leven
Source:Inhalation Toxicology, 3, 22, 179-191
Identifier: 290658
doi: doi:10.3109/08958370902828468
Keywords: Biology · Toxicology and Applied Pharmacology · Brown Norway rats · Respiratory allergy · Respiratory irritation · Sulfur dioxide · Trimellitic anhydride · Organisation · MSG - Modelling Simulation & Gaming · BSS - Behavioural and Societal Sciences


Irritant-induced inflammation of the airways may aggravate respiratory allergy induced by chemical respiratory allergens. Therefore, it was studied whether airway irritation by sulfur dioxide (SO<sub>2</sub>) would enhance respiratory allergic reactions to trimellitic anhydride (TMA), using a rat model. Brown Norway (BN) rats were topically sensitized, subsequently exposed for a single time or repeatedly to 300ppm SO<sub>2</sub>, and challenged by inhalation to a distinctly irritating or minimally irritating concentration of TMA after the (last) SO<sub>2</sub> exposure. Repeated exposure to SO <sub>2</sub> alone reduced breathing frequency during exposure, and caused epithelial alterations including hyperplasia and squamous metaplasia, and infiltration of polymorphonuclear inflammatory cells into nasal tissues, larynx, trachea, and bronchi/bronchioli. Histopathological changes were less prominent after 1 day of SO<sub>2</sub> exposure. Repeated pre-exposure to SO<sub>2</sub> reduced the number of TMA-induced apnoeas, in an SO<sub>2</sub> exposure duration-dependent manner. This effect of SO<sub>2</sub> on TMA-induced functional allergic reactions (apnoeas) was distinct only when the TMA challenge concentration was not too irritating itself. Repeated pre-exposure to SO <sub>2</sub> reduced TMA-induced laryngeal ulceration, goblet-cell hyperplasia, and inflammation in the lungs in most animals, regardless of the TMA challenge concentration. The SO<sub>2</sub>-induced replacement of normal respiratory epithelium by less sensitive, squamous epithelium may offer an explanation for the, unexpected, reduced allergic manifestation. However in a few animals, SO<sub>2</sub> appeared to facilitate TMA-induced irritation, probably due to incomplete protection. Overall, SO<sub>2</sub> exposure of TMA-sensitized rats reduced TMA-related allergic respiratory responses in most animals.