Teratogenic effects of methamphetamine in mice

Eight-day pregnant Jcl:ICR mice were administered methamphetamine hydrochloride i.p. at doses of 11, 13, 14, 15, 17, 19 and 21 mg/kg. The number of animals that died after the treatment increased dose-dependently. The highest maternal mortality rate (50%) was observed in the 21 mg/kg group. On day 18 of gestation, the animals were killed and fetuses were examined for external and skeletal malformations. The mortality and malformation rates of fetuses increased with the increase in dose, but both rates reached their highest levels at a dose of 19 mg/kg. Exencephaly, open eyelids, cleft palate and rib anomaly were frequently observed malformations. The single teratogenic dose was estimated to be 19 mg/kg for both external and skeletal malformations. This amount was about ten times the daily intake of many Japanese abusers. The risk of malformed infants being born to female abusers was considered to be high. More crowded conditions have been reported to increase the fetal malformation rate. The higher malformation rate in the 19 mg/kg group than in the 21 mg/kg group was considered to be due to fewer surviving mice in the 21 mg/kg group, because of a higher mortality rate.