Following the release of methyl isocyanate (MIC) from the Union Carbide plant in Bhopal, India, and the subsequent deaths of between 2 and 4,000 people, the Department of State, and the World Health Organization requested that the NTP examine the long term health effects of short exposures to MIC. In response, the NTP and NIEHS assembled staff with expertise in inhalation, reproductive, immuno-, genetic and general toxicology, along with staff experienced in pulmonary and general pathology, to design and implement studies which would provide a data base on this chemical. Animal studies were initiated in March of 1985 with exposure to MIC vapors accomplished in the Building 14 inhalation facility by personnel employed by Northrop. Rats and mice of both sexes were exposed to various concentrations of MIC for either two hours on one occasion, or for six hours on four consecutive days. Studies of complete animal histopathology were performed immediately following the exposures and at periodic intervals during the subsequent 90 days. Pulmonary effects were examined by light and electron microscopy, and were correlated with results of pulmonary function tests performed by the Pulmonary Physiology Testing Laboratory at EPA. Reproductive effects were examined by mating trials, and by evaluaton of offspring from late term pregnant mice exposed on gestation days 14-17. Evaluation of immunotoxicity included tests of humoral and cell mediated immunity. Genetic toxicity evaluations included a variety of in vitro assays, cytogenetic assays in vivo, and determinations of micronuclei, and dominant lethal assays in exposed mice.
