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


CONCLUSIONS
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.
Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden.
X D
XD
Zhang
H
H
Welinder
B A
BA
Jönsson
S
S
Skerfving
D000812:Anhydrides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization; D007073:Immunoglobulin E / Q000032:analysis*; D007074:Immunoglobulin G / Q000032:analysis*; D007271:Injections, Intradermal; D008297:Male; D011237:Predictive Value of Tests; D051381:Rats; D011914:Rats, Inbred BN; D018709:Statistics, Nonparametric; D013329:Structure-Activity Relationship
D000812:Anhydrides; D007074:Immunoglobulin G; D007073:Immunoglobulin E