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 escu lenta), was studied in rat. Groups of pregnant Sprague-Dawley rats rec eived 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 pre gnancy, 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 mug MMH/ml (lowest dose) to 0.60 mug MMH/ml (highest dose). The avera ge serum levels measured 45 min after the intragastric application (pe ak levels) were 0.28 mug MMH/ml and 1.6 mug MMH/ml, respectively. Seru m concentrations of MMH corresponding to those measured in the lower d ose groups in this study were seen in pilot studies after a single mus hroom meal in human volunteers. A dose-dependent, statistically signif icant increase in the number of resorptions was seen in all but the lo west dose group after the infusion of MMH. In addition, except for the two lowest doses, there was a dramatic, dose-dependent decrease in th e pregnancy rate as compared to controls, with no pregnancies occurrin g at the two highest dose level groups. The decreased pregnancy rate w as probably due to preimplantation loss which was shown to occur after a single intragastric bolus dose of MMH (5 mg/kg bw). No significant differences in the incidences of external and skeletal malformations a nd in fetal body weights were seen between the treated groups and cont rols in the two experiments. The results of the present study seem to warrant caution concerning the consumption of the false morel in women desiring pregnancy.