Toxicological studies of the false morel (Gyromitra esculenta): embryotoxicity of monomethylhydrazine in the rat.

The embryotoxic and teratogenic potential of monomethylhydrazine (MMH), a toxic component of the widely consumed false morel (Gyromitra esculenta), was studied in rat. Groups of pregnant Sprague-Dawley rats received MMH as a constant i.v. infusion via implanted osmotic minipumps (1.2, 3.0, 4.2, 6.0, 9.0 or 13.2 mg MMH/kg bw/day) on days 6-13 of pregnancy, or as a single intragastric bolus (1 mg MMH/kg/bw or 5 mg MMH/kg/bw) on day 6 of pregnancy. Controls received corresponding amounts of saline. The average maternal serum concentrations, measured during the infusion treatment with a sensitive HPLC method, ranged from 0.072 micrograms MMH/ml (lowest dose) to 0.60 microgram MMH/ml (highest dose). The average serum levels measured 45 min after the intragastric application (peak levels) were 0.28 microgram MMH/ml and 1.6 microgram MMH/ml, respectively. Serum concentrations of MMH corresponding to those measured in the lower dose groups in this study were seen in pilot studies after a single mushroom meal in human volunteers. A dose-dependent, statistically significant increase in the number of resorptions was seen in all but the lowest dose group after the infusion of MMH. In addition, except for the two lowest doses, there was a dramatic, dose-dependent decrease in the pregnancy rate as compared to controls, with no pregnancies occurring at the two highest dose level groups. The decreased pregnancy rate was probably due to preimplantation loss which was shown to occur after a single intragastric bolus dose of MMH (5 mg/kg bw).(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution characteristics of methyl-hydrazine in the plasma and cerebrospinal fluid of monkeys.

A Lumped parameter mathmatical model including extracellular fluid, intracellular fluid, and cerebrospinal fluid compartments has been applied to describe methylhydrazine (MMH) distribution kinetics in the blood and cerebrospinal fluid of Rhesus monkeys. Ten monkeys average weight 5.5 kg, were given intravenous infusions of MMH while blood and cerebrospinal fluid samples were periodically collected and analyzed for MMH. The mathematical model was used to simulate the infusions and the simulations were compared with experimental data to validate the model and to evaluate the mass transfer parameters required by the model.