TERATOLOGICAL ASSESSMENT OF STOBADINE AFTER SINGLE AND REPEATED ADMINISTRATION IN MICE

Teratological studies were performed with stobadine, a compound with a ntiarrhythmic and antihypoxic activity. Single i.v. injections of stob adine in the form of dihydrochloride (DH 1011) to ICR mice on days 3, 6, 9 or 12 of gestation at doses of 1 and 3 mg kg(-1) had no teratogen ic effect. Slight fetal toxicity was manifested by decreased fetal wei ght after treatment on days 3 and 6, increased incidence of rudimentar y ribs after treatment on days 9 and 12 of gestation and non-significa ntly increased postimplantation loss after injection on day 6 of gesta tion. The effect of repeated oral administration in the form of dipalm itate salt (DP 1031) was studied in doses; of 12.2, 61.0 and 122.0 mg kg(-1) on days 4-16 of gestation. Oral exposure to 61.0 mg kg(-1) DP 1 031 resulted in significant reduction of implantations, live fetuses a nd litter weight, and after 122.0 mg kg(-1) DP 1031 the fetal weight w as significantly decreased. External and skeletal examinations of the fetuses revealed no evidence of teratogenesis. The relevance of the tw o routes of stobadine administration for risk involvement is discussed .