The Bhopal accident and methyl isocyanate toxicity

Abstract

The Bhopal accident, the world's worst industrial disaster, in which nearly 40 metric tons of methyl isocyanate (MIC) was released from the Union Carbide pesticide plant, occurred nearly 10 yr ago during the night of December 2 and 3, 1984. Over 3000 people residing in areas adjacent to the plant died of pulmonary edema within 3 d of the accident. Follow-up studies revealed pulmonary, ophthalmic, reproductive, immunologic, neurological, and hematologic toxicity among the survivors. Despite high reactivity, MIC can traverse cell membranes and reach distant organs, perhaps as a reversible conjugate with glutathione, which may explain some of the systemic effects of MIC. MIC can be degraded as a result of pyrolysis and interaction with water, but none of the breakdown products can duplicate the toxicity observed in Bhopal and in animal models. MIC may be the most toxic of all isocyanates because of its very high vapor pressure relative to other isocyanates and because of its ability to exert toxic effects on numerous organ systems.

Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases

“…Activation of TRPA1 by industrial isocyanates may have contributed to the acute and chronic health effects experienced by victims of the Bhopal incident and by agricultural and industrial laborers (1,6). We show that industrial isocyanates strongly activate human TRPA1 channels and, in mice, have effects very similar to those of tear gases, activating trigeminal nerve endings in the eyes and facial area to elicit nocifensive responses.…”

“…In these accidents, metam sodium reacted with soil components and water to produce MIC and other reactive agents (3)(4)(5). MIC exposure caused immediate unbearable irritation of eyes, nose, and throat (6). The airways are especially sensitive to MIC and other isocyanates.…”

Effects of exposure of parents to toxic gases in Bhopal on the offspring

“…because of its high chemical reactivity [Varma, 1986;Varma and Mulay, 2006]. The controversies were the following: first, given the high chemical reactivity of MIC, can it produce systemic effect or will its effects be limited to exposed surface such as the eye [Andersson et al, 1984]?…”

“…Cherry-red venous blood was more probably caused by hemoconcentration rather than as a result of MIC-hemoglobin interaction [Jeevaratnam and Vaidyanathan, 1992]. Furthermore, MIC can cause ocular, pulmonary and other effects notwithstanding its high chemical reactivity [Varma, 1986;Bucher, 1987;Kamat et al, 1992;Vijayan and Sankaran, 1996;Dhara and Dhara, 2002;Varma and Mulay, 2006]. As well, MIC can interact with proteins [Brown et al, 1987], act as a hapten [Karol et al, 1987] and rapidly cross the placenta [Ferguson et al, 1988].…”

“…Just past the midnight of December 2-3, 1984, approximately 40 metric tons of methyl isocyanate (MIC) and other toxic gases escaped from the Union Carbide Pesticide Plant in Bhopal, India, within a period of 45-60 min resulting in over 5,000 acute deaths and long-term effects in thousands of survivors [Varma, 1986;Bucher, 1987;Kamat et al, 1992;Vijayan and Sankaran, 1996;Dhara and Dhara, 2002;Varma and Mulay, 2006]. At the time of the Bhopal disaster, it was conjectured that the high chemical reactivity of MIC would result in its destruction upon contact with body surface and no systemic toxicity would follow [Varma, 1986]; this speculation and anecdotal reports of cyanide rather than MIC poisoning greatly influenced both clinical and experimental studies [Varma, 1986;Varma and Mulay, 2006].…”