Document Detail

Respiratory hypersensitivity to trimellitic anhydride in Brown Norway rats: a comparison of endpoints.
MedLine Citation:
PMID:  11920932     Owner:  NLM     Status:  MEDLINE    
A rat bioassay has been developed to provide an objective approach for the identification and classification of respiratory allergy using trimellitic anhydride (TMA), which is a known respiratory tract irritant and asthmagen. Particular emphasis was placed on the study of route-of-induction-dependent effects and their progression upon inhalation challenge with TMA (approximately 23 mg m(-3) for a duration of 30 min), which included analysis of specific and non-specific airway hyperreactivity and pulmonary inflammation initiated and sustained by immunological processes. Refinement of the bioassay focused on procedures to probe changes occurring upon challenge with TMA or methacholine aerosols using physiological, biochemical and immunological procedures. Following challenge with TMA, the rats sensitized to TMA showed marked changes in peak inspiratory and expiratory air flows and respiratory minute volume. In these animals, a sustained pulmonary inflammation occurred, characterized by specific endpoints determined in bronchoalveolar lavage (lactate dehydrogenase, protein, nitrite, eosinophil peroxidase, myeloperoxidase). When compared with the naive controls, lung weights were increased significantly, as were the weights of lung-associated lymph nodes following inhalation induction and auricular lymph nodes following topical induction. The extent of changes observed was equal or more pronounced in animals sensitized epicutaneously (day 0:150 microl vehicle/50% TMA on each flank, day 7; booster administration to the skin of the dorsum of both ears using half the concentration and volume used on day 0) when compared with rats sensitized by 5 x 3 h day(-1) inhalation exposures (low dose: 25 mg TMA m(-3), high dose: 120 mg TMA m(-3)). In summary, the findings support the conclusion that the Brown Norway rat model is suitable for identifying TMA as an agent that causes both an immediate-type change of breathing patterns and a delayed-type sustained pulmonary inflammatory response. However, it remains unresolved whether the marked effects observed in the topically sensitized rats are more related to a route-of-induction or dose-dependent phenomenon.
Jürgen Pauluhn; Petra Eidmann; Alexius Freyberger; Grazyna Wasinska-Kempka; Hans-Werner Vohr
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of applied toxicology : JAT     Volume:  22     ISSN:  0260-437X     ISO Abbreviation:  J Appl Toxicol     Publication Date:    2002 Mar-Apr
Date Detail:
Created Date:  2002-03-28     Completed Date:  2002-08-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8109495     Medline TA:  J Appl Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  89-97     Citation Subset:  IM    
Copyright Information:
Copyright 2002 John Wiley & Sons, Ltd.
Institute of Toxicology, Bayer AG, Building 514, 42096 Wuppertal, Germany.
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MeSH Terms
Administration, Cutaneous
Administration, Inhalation
Allergens / administration & dosage,  toxicity*
Bronchoalveolar Lavage Fluid / chemistry*,  cytology*
Bronchoconstrictor Agents / toxicity
Drug Administration Schedule
Hypersensitivity, Delayed / chemically induced
Hypersensitivity, Immediate / chemically induced
Lung / immunology,  pathology
Methacholine Chloride / toxicity
Organ Size
Phthalic Anhydrides / toxicity*
Rats, Inbred BN
Respiratory Function Tests
Respiratory Hypersensitivity / chemically induced*,  physiopathology
Respiratory Mechanics / drug effects,  physiology
Time Factors
Reg. No./Substance:
0/Aerosols; 0/Allergens; 0/Bronchoconstrictor Agents; 0/Phthalic Anhydrides; 552-30-7/trimellitic anhydride; 62-51-1/Methacholine Chloride

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