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.

Bhopal Gas Tragedy: review of clinical and experimental findings after 25 years

“…Though titres were low and transient (declining after several months), these findings indicate that the single large exposure to MIC elicited a definite immunologic response. This was concomitant with chronic respiratory effects following MIC exposure [32].…”

Genotoxic and Carcinogenic Effects of Methyl Isocyanate (MIC) Reviewed on Exposed Bhopal Population and Future Perspectives for Assessment of Long-Term MIC-Effect

“…Reduced response to T and B cell mitogens was reported in 71% of the exposed population. Low titers of IgG, IgM and IgE class of antibodies were noticed in 11% of the exposed cases [52]. MIC-specific antibodies were correlated with severity of lung damage [53]; though MIC didn't reveal any synergistic effect on humoral immunity in MIC-exposed protein deficient people [54].…”

“…MIC was negative in the male mouse dominant lethal assay [19]. Altogether, lowtiter and transient antibody response was noticed in exposed human and animals [21].…”

“…The reactions of MIC with non-essential functional groups and the highly exothermic hydrolysis reaction would both act to compete with an interaction with specific enzymes or proteins during inhalation exposures. However, the modification of functional groups can apparently lead to antibody-formation as shown by Karol and coworkers in experimental animals and in survivors of the Bhopal accident [21]. However, the significance of these findings in relation to the overall health effects of MIC exposure will require further study.…”

Methyl Isocyanate

“…Reversible conjugation of isocyanates with glutathione , which occurs both spontaneously and enzymatically, may have been the mechanism of distributing MIC molecules to different parts of the body and the reason behind its diffuse toxicity profile (Baillie and Slatter, 1991;Pearson et al, 1991). MIC can act as a hapten, which leads to the generation of antibodies in both animals and humans (Karol et al, 1987). MIC can carbamylate macromolecules (Segal et al, 1989).…”