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Respiratory irritation by trimellitic anhydride in Brown Norway and Wistar rats

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Author: Arts, J.H.E. · Koning, · Bloksma, N. · Kuper, C.F.
Institution: TNO Voeding
Source:Inhalation Toxicology, 8, 13, 719-728
Identifier: 236225
Keywords: trimellitic anhydride · animal experiment · article · breathing pattern · concentration response · controlled study · female · lung function · lung weight · nonhuman · priority journal · rat · rat strain · respiratory tract allergy · statistical analysis · Administration, Inhalation · Algorithms · Anhydrides · Animals · Female · Immunoglobulin E · Irritants · Lung · Metals · Organ Size · Particle Size · Rats · Rats, Inbred BN · Rats, Wistar · Respiratory Function Tests · Respiratory Tract Diseases · Animalia · Rattus norvegicus


Several acid anhydrides are known for their sensitizing and irritative properties. Since both irritation and respiratory allergy can cause changes of lung function, proper testing of allergen-dependent effects on the respiratory tract requires knowledge of the respiratory irritant effects. To study the latter effects, groups of female Brown Norway (BN) and Wistar rats were exposed for 30 min to a range of concentrations (10 to 300 mg/m3) of the well-known respiratory allergen trimellitic anhydride (TMA). Breathing pattern and frequency were monitored before, during, and after exposure. Animals were necropsied and lung weights were determined 1 day after exposure. In BN rats, changes in breathing pattern were seen at levels of 29 mg/m3 and higher and decreases in frequency at 60 mg/m3 and higher, whereas in Wistar rats changes in both pattern and frequency (increases followed by decreases) were seen at levels of 34 mg/m3 and higher. Changes in breathing pattern consisted of a spiked form instead of a wave form of the respiratory cycle, with a pause between breaths at the end of expiration. The length of the pause increased with increasing concentrations of TMA while the duration of the respiratory cycle decreased slightly, implying that breathing frequency was mainly determined by the magnitude of the increase in pause. These reversible changes in breathing pattern and frequency were considered to be suggestive of lower airway irritation, rather than upper airway irritation. No concentration-related changes in lung weights were observed. The highest level at which no acute airway irritation as based on both breathing pattern and frequency was observed in both rat strains was 14 mg/m3.