Dissociation between maternal and fetal toxicity of methyl isocyanate in mice and rats.

  title={Dissociation between maternal and fetal toxicity of methyl isocyanate in mice and rats.},
  author={Daya R. Varma and I Guest and S. Smith and Shree Mulay},
  journal={Journal of toxicology and environmental health},
  volume={30 1},
  • D. Varma, I. Guest, S. Mulay
  • Published 1 May 1990
  • Medicine, Biology, Chemistry
  • Journal of toxicology and environmental health
The contribution of maternal hormonal changes and pulmonary damage on the fetal toxicity of methyl isocyanate (MIC) was studied in mice and rats. Exposure to MIC decreased maternal plasma progesterone levels in mice that lost but not in mice that retained pregnancy. Fetal toxicity of MIC was not related to changes in maternal plasma corticosterone levels. Neither chronic administration of progesterone nor the suppression of pulmonary edema with dexamethasone decreased fetal toxicity of MIC… 
Developmental toxicity of methylamines in mice.
  • I. GuestD. Varma
  • Chemistry, Biology
    Journal of toxicology and environmental health
  • 1991
The ability of methylamines to adversely affect fetal development suggests that these amines, especially trimethylamine, may act as endogenous teratogens under certain conditions.
Teratogenic and macromolecular synthesis inhibitory effects of trimethylamine on mouse embryos in culture.
It is concluded that TMA exerts teratogenic effects on mouse embryos in culture and inhibits their growth by reducing macromolecular synthesis; these effects may not involve glutathione depletion or generation of free radicals.
Toxicity of the methyl isocyanate metabolite S-(N-methylcarbamoyl)GSH on mouse embryos in culture.
It is concluded that SMG exerts embryotoxic and dysmorphogenic effects and may contribute to systemic toxicity of methyl isocyanate.
Embryotoxicity study of monomeric 4,4'-methylenediphenyl diisocyanate (MDI) aerosol after inhalation exposure in Wistar rats.
A substance-induced effect in the high-dose group cannot be excluded with certainty, although the relevance of an increase of this minor anomaly in doses which cause toxic effects in dams is limited and the number observed is within the limits of biological variability.
Embryotoxic and teratogenic effects of intraperitoneally administered metavanadate in mice.
Maternal toxicity was observed at 2, 4, and 8 mg/kg/d as evidenced by decreased weight gain during treatment, while the lowest-observed-adverse-effect level (LOAEL) for maternal toxicity was 2 mg NaVO3/kg/.
The Bhopal accident and methyl isocyanate toxicity.
MIC may be the most toxic of all isocyanates because of its very high vapor pressure relative to other isocianates andBecause of its ability to exert toxic effects on numerous organ systems, which may explain some of the systemic effects of MIC.
Effects of Cocaine on Rat Embryo Development in Vivo and in Cultures
It is concluded that cocaine possesses teratogenic potential that may be partly independent of maternal toxicity and was more toxic than procaine.
Scientific Basis for Swedish Occupational Standards XXII
In studies in which pregnant pigs and rats were fed on cassava containing up to 1250 mg KCN/kg, the only observed toxic effects on reproduction were minor metabolic differences and lower relative organ weights in fetuses at doses affecting the mothers.
Pregnancy complications in Bhopal women exposed to methyl isocyanate vapor
Pregnancy loss was higher in women who were in their first (58.8%) than in those who are in their second or third trimester of pregnancy during the MIC spill, and the 1–30‐day mortality rate was significantly greater than that recorded for the two years preceding the accident.


Reproductive toxicity of methyl isocyanate in mice.
The studies show that the effects of MIC in mice mimic many of the reproductive complications in Bhopal, with evidence of an increase in visceral abnormalities and a decrease in fetal and placental weights and in fetal skeleton sizes.
Methyl isocyanate: reproductive and developmental toxicology studies in Swiss mice.
Exposure of male and female mice to 1 or 3 ppm given 6 hr per day for 4 consecutive days had no effect on reproduction during mating trials conducted 1, 8, and 17 weeks after the exposure period, and there was no evidence of a dominant lethal effect in exposed male mice.
Inhibition of methyl isocyanate toxicity in mice by starvation and dexamethasone but not by sodium thiosulfate, atropine, and ethanol.
Effects of starvation (24 and 48 h), dexamethasone, sodium thiosulfate, atropine, and ethanol on the toxicity of methyl isocyanate (MIC) vapor, which escaped during the Bhopal accident of December 3,
Epidemiological and experimental studies on the effects of methyl isocyanate on the course of pregnancy.
  • D. Varma
  • Medicine
    Environmental health perspectives
  • 1987
It was found that 43% of pregnancies in women residing near the Union Carbide pesticide plant did not result in the birth of a live child and experimental studies on the effects of MIC in pregnant mice corroborate the epidemiological data from Bhopal.
Myelotoxicity induced in female B6C3F1 mice by inhalation of methyl isocyanate.
The effects of a 4-day inhalation exposure to 0, 1, and 3 ppm methyl isocyanate on bone marrow parameters in female mice were examined at 5, 8, and 21 days following exposure, suggesting that the bone marrow may be a sensitive endpoint for MIC exposure in mice.
Influence of protein deficiency in rats on hormonal status and cytoplasmic glucocorticoid receptors in maternal and fetal tissues.
It is suggested that lower levels of plasma corticosterone and progesterone and high levels of liver glucocorticoid receptors in protein-deficient rats might be related to some of the adverse consequences of maternal malnutrition on fetal development.
Methyl isocyanate: an evaluation of in vivo cytogenetic activity.
The results demonstrate that exposure to MIC by inhalation results in bone marrow damage, indicating the systemic genotoxic/cytotoxic activity of MIC and/or reactive metabolites.
Cardiopulmonary effects in awake rats four and six months after exposure to methyl isocyanate.
Decreased dynamic compliance and changes in two new measures of lung function (volume and time at zero expiratory intrapleural pressure) suggest that MIC-induced lung dysfunction also exhibited elements of a restrictive disease.