Methyl Isocyanate and Carcinogenesis: Bridgeable Gaps in Scientific Knowledge

Abstract

Methyl isocyanate may have a role in cancer etiology, although the link is unclear. There is evidence in the literature that it can induce cancer in animals but the carcinogenic potency is weak. Pheochromocytoma of adrenal medulla and acinar cell tumors of pancreas have been observed in methyl isocyanate exposed animals. Conversely, emerging data from population-based epidemiological studies are contradictory since there is no evidence of such cancers in methyl isocyanate exposed humans. Recently, we reported a high prevalence of breast and lung cancers in such a population in Bhopal. In vitro findings appearing in the latest scientific literature suggest that genomic instability is caused by methyl isocyanate analogs in lung, colon, kidney, ovary epithelial cells, and that hepatocytes may undergo oncogenic transformation, have obvious implications. The conflicting information prompted us to present this update over the last three decades on methyl isocyanate-induced cancers after an extensive literature search using PubMed. While the pertinent literature remains limited, with a scarcity of strong laboratory analyses and field-epidemiological investigations, our succinct review of animal and human epidemiological data including in vitro evidences, should hopefully provide more insight to researchers, toxicologists, and public health professionals concerned with validation of the carcinogenicity of methyl isocyanate in humans.

In silico docking of methyl isocyanate (MIC) and its hydrolytic product (1, 3-dimethylurea) shows significant interaction with DNA Methyltransferase 1 suggests cancer risk in Bhopal-Gas-Tragedy survivors

“…Besides, the immunotoxic (Karol et al, 1987), genotoxic (Conner et al, 1987;Tice et al, 1987), reproductive and developmental toxic effects (Schwetz et al, 1987) are well-documented in humans and animals. However, the etiology of MIC in carcinogenesis is far from completely understood (Senthilkumar et al, 2012;Senthilkumar, 2012). Data from animal studies have shown that the carcinogenic potency of MIC is low and weak (Gassert et al, 1986;Ennever and Rosenkranz, 1987;Bucher and Uraih, 1989).…”

“…Evidence from in vitro studies suggest MIC-induced oncogenic transformation in human cells (Mishra et al, 2009abc;Raghuram et al, 2010;Hariom and Mishra, 2011;. But still, toxic chemical substances analyzing agencies are categorizing MIC as a non-carcinogenic substance (Senthilkumar et al, 2012).…”

Susceptibility of the Bhopal–methyl isocyanate (MIC)–gas–tragedy survivors and their offspring to COVID-19: What we know, what we don’t and what we should?

“…Undoubtedly, another group who should be in the debate is the life-threatening chemical exposed people surviving with chronic respiratory disorders. Here, we emphasize one such population who faced the World's worst chemical disaster in 1984 in Bhopal (Figure 1), survived the deadly methyl isocyanate (MIC) exposure with multiple complications including cancers [5][6][7] , pulmonary function abnormalities 8 , and obstructive lung function 9 . Almost thirty-five years over, the MIC-exposed long-term survivors and their offspring born post-exposure (also referred to as the Bhopal MIC-affected population) and their health status remain controversial.…”

Determination of methyl isopropyl hydantoin from rat erythrocytes by gas-chromatography mass-spectrometry to determine methyl isocyanate dose following inhalation exposure

“…Methyl isocyanate (MIC) is used for carbamylation of amines as an important precursor for the synthesis of carbamate pesticides and diisocyanates (i.e., intermediates in synthesis of plastics) (1–3). Although industrially important, MIC is also highly toxic, as tragically demonstrated by Bhopal disaster in 1984, where it is estimated that 8000 or more people died within minutes of exposure to MIC (4–6).…”