Respiratory Irritation by Trimellitic Anhydride in Brown Norway and Wistar Rats

Abstract

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/m(3)) 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/m(3) and higher and decreases in frequency at 60 mg/m(3) and higher, whereas in Wistar rats changes in both pattern and frequency (increases followed by decreases) 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 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/m(3).

Trimellitic anhydride (TMA) dust induces airway obstruction and eosinophilia in non-sensitized guinea pigs

“…Because the TMA-induced changes in respiratory cycle timing were similar to those caused by the known bronchoconstrictors histamine and acetylcholine, Schaper and Brost (1991) suggested that changes induced by TMA aerosol in non-sensitized mice were indicative of airway constriction. Arts et al (2001) challenged non-sensitized rats with aerosols of TMA in acetone and noted changes in respiratory frequency and pattern that were similar to those observed by Schaper and Brost (1991) in mice. Neither study in non-sensitized mice nor rats measured changes in pulmonary resistance or lung compliance after TMA challenge.…”

“…Peptides released by stimulation of neurons in the respiratory tract can cause bronchoconstriction and inflammation (Ricciardolo, 2001). Schaper and Brost (1991) using non-sensitized mice, and similarly Arts et al (2001) using non-sensitized rats, suggested that observed changes in respiratory cycle timing following TMA challenge were indicative of reflex bronchoconstriction in the lower respiratory tract. However, Arts et al (2001) noted that TMA was not like typical pulmonary irritants in that there was a rapid onset of response, increased respiratory frequency at low TMA concentrations, rapid recovery following exposure, no change in tidal volume and no change in lung weights due to edema.…”

“…Schaper and Brost (1991) using non-sensitized mice, and similarly Arts et al (2001) using non-sensitized rats, suggested that observed changes in respiratory cycle timing following TMA challenge were indicative of reflex bronchoconstriction in the lower respiratory tract. However, Arts et al (2001) noted that TMA was not like typical pulmonary irritants in that there was a rapid onset of response, increased respiratory frequency at low TMA concentrations, rapid recovery following exposure, no change in tidal volume and no change in lung weights due to edema. Regardless of the mechanism, this study demonstrates that TMA dust causes airway obstruction and eosinophilia in the absence of a latent period of sensitization.…”

“…In addition, studies monitoring respiratory patterns in nonsensitized mice and rats have suggested TMA causes airway obstruction (Schaper and Brost, 1991;Arts et al, 2001). However, in non-sensitized guinea pigs following inhalation of TMA dust, pulmonary resistance did not significantly increase relative to pre-challenge values (Obata et al, 1992).…”

Inhaled Multiwalled Carbon Nanotubes Modulate the Immune Response of Trimellitic Anhydride–induced Chemical Respiratory Allergy in Brown Norway Rats

“…Breathing pattern, respiratory frequency, and tidal volume were monitored every minute for 20 sec/min at 1 day before the first challenge, during, and directly after the challenge, and again 24 hr after the challenge with 15-mg/m 3 TMA (a nonirritating concentration; Arts et al 2001). 1132 STAAL ET AL.…”