Cross-reactivity of acid anhydrides assessed by airway challenge in rats sensitized with trimellitic anhydride (TMA).
Zhang-X; Fedan-JS; Lewis-DM; Siegel-PD
Toxicologist 2004 Mar; 78(S-1):49
Previous studies using inhaled organic acid anhydride (OAA)-protein conjugates in studies of airway hyperreactivity have revealed immunologic cross-reactivity among OAAs. The present investigation evaluated cross reactivity between phthalic anhydride, (PA), tetrachlorophthalic anhydride (TCPA) and TMA with respect to their ability to induce asthma-like airway responses in TMA-hapten-sensitized Brown Norway rats. Four to 40 mg of dry TMA powder was applied to anesthetized rats' backs (hair removed with scissors) on days 0, 7, 14 and 21 and washed off with water 4 hours after each application. Inhalation challenge with TMA aerosol (40 mg/m 3, 10 min) was performed on day 35 and Penh, an index of airway resistance, was measured. The sensitized rats developed early (EAR)- and late(LAR)-phase obstructive responses. One week after TMA inhalation exposure, rats were challenged with TMA, PA or TCPA aerosol (40mg/m 3, 10 min; n = 8 in each group). EAR developed in all rats challenged with TMA, 3 rats challenged with PA, and 7 rats challenged with TCPA. The LAR developed in all TMA-challenged, sensitized rats, but none of the TMA sensitized rats challenged with PA or TCPA developed the LAR. We have previously reported that low dose TMA airway challenge results in EAR-only similar to the airway responses observed in the present cross-reactivity studies. It is concluded that cross-reactivity exists between TMA and both PA and TCPA. These airway responses are most likely immune mediated and the reason why this cross-reactivity was manifested only by EAR may be related to lower relative antigenic potency of PA and TCPA to that of TMA in TMA-sensitized rats.
Acids; Anhydrides; Airway-obstruction; Airway-resistance; Laboratory-animals; Animals; Animal-studies; Organic-acids; Aerosols
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland