Original article

Scand J Work Environ Health 1998;24(3):220-227    pdf


Antibody responses of rats after immunization with organic acid anhydrides as a model of predictive testing

by Zhang X-D, Welinder H, Jönsson BAG, Skerfving S

Objectives The sensitizing properties of organic acid anhydrides (OAA) were evaluated in a rat model.

Methods The development of specific immunoglobulin (Ig) E and Ig G in serum was investigated after immunization with 14 OAA and 3 OAA conjugates. Brown Norway rats were injected intradermally with 0.1 ml of 0.2 M OAA in liquid paraffin or 1.4 mg of rat serum albumin conjugate in saline. Serum samples were collected after 4 weeks. Antibodies were analyzed with enzyme-linked immunosorbent assay.

Results The serum titers of specific Ig E after immunization with the different free OAA varied from <50 to 6400. The rats immunized with 4-methylphthalic anhydride exhibited the highest titers. The specificity of Ig E was demonstrated by enzyme-linked immunosorbent assay inhibition tests. A good correlation was observed between the Ig E and Ig G titers. Immunization with OAA conjugates showed results parallel to the findings for the free compounds. Importantly, the Ig E titers for the OAA agreed well with findings from guinea pigs and with literature data from epidemiologic studies of exposed workers.

Conclusion The present animal model may be a valuable tool for predicting the sensitizing potential of OAA and possibly the sensitizing potential of low-molecular-weight compounds in general. Furthermore, the antibody specificity of the haptens and the variations in the magnitude of the antibody titers indicate a valuable approach for studies of quantitative structure-activity relationships.

The following articles refer to this text: 2001;27(2):133-139; 2001;27(5):327-334