Respiratory irritation by trimellitic anhydride in Brown Norway and Wistarrats

Several acid anhydrides are known for their sensitizing and irritative prop erties. Since both irritation and respiratory allergy can cause changes of lung function, proper testing of allergen-dependent effects on the respirat ory 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/m(3)) of the well-known respiratory allergen trimellitic anhydride (TMA). Breathing pat tern and frequency were monitored before, during, and after exposure. Anima ls were necropsied and lung weights were determined 1 day after exposure. I n BN rats, changes in breathing pattern were seen at levels of 29 mg/m(3) a nd higher and decreases in frequency at 60 mg/m(3) and higher, whereas in W istar rats changes in both pattern and frequency (increases followed by dec reases) were seen at levels of 34 mg/m(3) and higher. Changes in breathing pattern consisted of a spiked form instead of a wave form of the respirator y cycle, with a pause between breaths at the end of expiration. The length of the pause increased with increasing concentrations of TMA while the dura tion of the respiratory cycle decreased slightly, implying that breathing f requency was mainly determined by the magnitude of the increase in pause. T hese reversible changes in breathing pattern and frequency were considered to be suggestive of lower airway irritation, rather than upper airway irrit ation. No concentration-related changes in lung weights were observed. The highest level at which no acute airway irritation as based on both breathin g pattern and frequency was observed in both rat strains was 14 mg/m(3).