The antibody response to methyl isocyanate: experimental and clinical findings

Abstract

As a result of the industrial accident in Bhopal, India (December 1984) in which thousands of people were exposed to methyl isocyanate (MIC), concern was raised for possible long-term health effects. The well-recognized immunologic consequences of exposure to other industrial isocyanates prompted investigation of an antibody response to MIC. Using procedures which had been developed in this laboratory to evaluate isocyanate immunotoxicity, animal studies were undertaken to develop and test reagents which could be used to detect antibodies to MIC in the exposed population. Guinea pigs were injected with MIC in its reactive isocyanate form. Three weeks later, blood was drawn and serum evaluated using ELISA. To detect antibodies, an antigen was prepared by reaction of MIC with guinea pig serum albumin. Antibodies were detected in each of the four animals injected with MIC. Titers achieved were 1:5120 to 1:10,240. Inhibition assays revealed antibody specificity directed toward the MIC hapten. Analogous antigens prepared by reaction of MIC with human serum albumin were used to evaluate sera from individuals exposed in Bhopal to MIC. Antibodies were detected in 12 of 144 exposed persons. Antibodies were specific for MIC, as evidenced by inhibition assays, and belonged to the IgG, IgM and IgE classes. However, titers were generally low and transient and were found in persons having had the highest MIC exposures. Total IgE values of sera were not significantly different from those of control sera obtained from Bombay residents. The results indicate that exposure to methyl isocyanate resulted in production of specific antibodies. However, the low titers observed and the transient nature of the response suggest little health consequence should result form the antibody response.