Respiratory allergy and pulmonary irritation to trimellitic anhydride in Brown Norway rats

Occupational exposure to low-molecular-weight (LMW) allergens such as acid anhydrides can result in occupational asthma, an allergic disease characterized by episodic airway obstruction, airways inflammation, and non specific airways hyperresponsiveness. Since LMW irritants can provoke rather simila...

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Published in:Toxicology and applied pharmacology 2003-02, Vol.187 (1), p.38-49
Main Authors: Arts, Josje H.E, Bloksma, Nanne, Leusink-Muis, Thea, Kuper, C.Frieke
Format: Article
Language:English
Subjects:
Airway irritation
Allergens - toxicity
Animals
Biological and medical sciences
Body Weight - drug effects
Bronchoalveolar Lavage Fluid - chemistry
Brown Norway rats
Chemical and industrial products toxicology. Toxic occupational diseases
Female
Immunization
Immunoglobulin E - blood
Lung - drug effects
Lung - pathology
Medical sciences
Nonspecific airway hyperresponsiveness
Organ Size - drug effects
Phthalic Anhydrides - toxicity
Rats
Rats, Inbred BN
Respiration - drug effects
Respiratory allergy
Respiratory Function Tests
Toxicology
Trimellitic anhydride
Various organic compounds
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Summary:Occupational exposure to low-molecular-weight (LMW) allergens such as acid anhydrides can result in occupational asthma, an allergic disease characterized by episodic airway obstruction, airways inflammation, and non specific airways hyperresponsiveness. Since LMW irritants can provoke rather similar effects and since most, if not all, LMW allergens have irritant properties, this study addressed the distinction between allergenic and irritant effects of the respiratory allergen trimellitic anhydride (TMA). BN rats were sensitized by dermal application of TMA or vehicle alone and 3 weeks later were challenged by inhalation of a slightly irritating concentration of TMA or the vehicle. Lung function was measured before, during, and shortly after challenge. One day after challenge, in vivo and in vitro nonspecific airways hyperresponsiveness to methacholine was measured, and bronchoalveolar lavage was performed to measure total protein, lactate dehydrogenase, N-acetyl-glucosaminidase, and total and differential leukocyte numbers in the fluid. In addition, IgE measurements and histopathological examinations of the respiratory tract were carried out. TMA challenge of sensitized, but not sham-sensitized, BN rats reduced breathing frequency during challenge, elevated total and TMA-specific serum IgE levels, and caused a typical allergic asthma-associated airway pathology, as observed earlier. Vehicle challenge did not cause these effects, irrespective of sensitization. Hyperresponsiveness to methacholine was only seen in TMA-sensitized and -challenged rats. These rats also showed increased levels of the biochemical parameters and increased numbers of eosinophils and neutrophils in the lung lavage fluid; TMA challenge of sham-sensitized rats caused similar but markedly less pronounced effects. During TMA challenge of sham-sensitized rats, a breathing pattern typical of irritation was noticed but a clearly distinct pattern was seen upon TMA challenge of sensitized rats. In conclusion, TMA challenge of sensitized rats caused sensitization-dependent asthma-like early changes in breathing pattern that clearly could be distinguished from irritant-induced changes and non-specific airways hyperresponsiveness 24 h after challenge. Sensitization-dependent functional changes were accompanied by inflammatory changes characteristic of asthma and biochemical evidence of airway damage.
ISSN:0041-008X
1096-0333
DOI:10.1016/S0041-008X(02)00023-6