Relationship between chemical structure and airway sensitizing potential for organic acid anhydrides : an animal model

Sammanfattning: Oranic acid anhydrides (OAAs) are important reactive, low-molecular-weight industrial chemicals which induce allergic rhinitis and asthma in exposed subjects. Specific IgE has been demonstrated in a large proportion of OAA-exposed workers. The characteristics of the OAAs make them excellent model compounds for studies of quantitative structure-activity relationships (QSAR) of allergenicity. In the present work, guinea pigs (GPs) and rats were intradermally immunized with various OAAs, and induced IgE and IgG titers were analyzed by ELISA. GPs gave positive airway responses after sensitization to free OAAs and challenge with the corresponding GP serum albumin conjugates, and the airway responses were closely related to the IgG1 titers. Various OAAs showed a wide range in antibody titers. Ring structure, the position of double bonds, and methyl group substitution affected the immunogenicity of the OAAs. The hapten specificity of the antibodies and the QSAR were proved by in-vitro and in-vivo inhibition tests of cross-reactivity. There was a good agreement between the titers of induced GP IgG1 and rat IgE after sensitization to the various OAAs. Further, the results of the animal models were in good correspondence with findings in OAA-exposed workers. Thus, the models may be used to predict the sensitizing potential of OAAs, and possibly other low-molecular-weight compounds, and may also be valuable tools for the evaluation of QSAR.