Reproductive toxicity of methyl isocyanate in mice

The effects of methyl isocyanate (MIC) vapor on pregnancy and fertility were studied in mice in view of the reported increase in reproductive complications in Bhopal following the December 3, 1984, accident. The whole-body exposure of mice to 9 and 15 ppm MIC for 3 h on d 8 of gestation led to resorption of greater than 80% of implants. In more than 75% of MIC-exposed animals, all implants were lost. At these concentrations, MIC did not cause external malformations. However, there was evidence of an increase in visceral abnormalities and a decrease in fetal and placental weights and in fetal skeleton sizes. MIC disturbed the estrus cycle and decreased the mating and pregnancy rate of female mice. The mating performance of MIC-exposed male mice was also decreased. Exposure to MIC increased serum corticosterone levels of male and nonpregnant female mice. MIC exerted no significant effects on serum corticosterone and progesterone levels of pregnant mice if the pregnancy was retained but caused a significant decrease in the serum levels of these two hormones in animals that lost all the implants. These studies show that the effects of MIC in mice mimic many of the reproductive complications in Bhopal. The mechanism of the reproductive toxicity of MIC remains to be identified.