Dose-response and time course of specific IgE and IgG after single and repeated topical skin exposure to dry trimellitic anhydride powder in a Brown Norway rat model

Background: Trimellitic anhydride (TMA)-induced occupational asthma is thought to be associated with its ability to acylate proteins and to induce production of TMA-specific immunoglobulin (Ig)E. Though the respiratory tract is considered to be a major exposure route leading to airway sensitization, the potential role of dermal exposure producing asthmatic sensitization is not known. The present study examines the ability of dry TMA powder to sensitize Brown Norway rats when applied, topically, to the skin. Methods: A patch of hair was carefully clipped with scissors on the rat's back. Dry TMA powder (0.3, 1.25, 5 and 20 mg) was administered on days 0, 7, 14 and 21, and the area occluded with surgical tape overnight after each application. Residual powder recovered from the occluded skin was analyzed by proton nuclear magnetic resonance and was still predominantly TMA. Circulating anti-TMA IgE and IgG were measured by ELISA. Results: TMA elicited dose-dependent production of specific IgE and IgG. Specific antibodies were detectable 2 weeks after the first TMA exposure and peaked between 3 and 4 weeks. Conclusion: The data suggest that topical skin exposure to dry TMA powder can induce allergic/immunological sensitization as demonstrated by the production of specific antibodies.