stevioside and Abnormalities--Drug-Induced

The developmental toxicity of steviol, a metabolite of stevioside, was studied in hamsters. Pregnant hamsters were intubated with steviol at dose levels of 0, 0.25, 0.5, 0.75 and 1.0 g/kg BW/day on days 6-10 of gestation. Steviol at doses of 0.75 and 1.0 g/kg BW/day were highly toxic to both dams and fetuses. Significant decrease of maternal body-weight gain during the experimental period (days 6-14) and high percentage of maternal mortality indicated the general toxicity of these two high doses. The number of live fetuses per litter and mean fetal weight also significantly decreased in the steviol-treated animals at doses of 0.75 and 1.0 g/kg BW day. The animals treated with an intermediate dose (0.50 g/kg BW/day) exhibited less signs of maternal and developmental toxicity than the two high doses (0.75 and 1.0 g/kg BW/day). One craniomeningocele was found in a fetus under the maternal toxic condition in steviol-treated at a dose of 0.75 g/kg BW/day. Neither the skeleton nor visceral development of the offspring was affected by steviol treatment except delayed ossification of the xiphoid (bifid) and long bones of the limbs and supernumerary thoracic ribs (14th ribs) tended to be increased at doses of 0.5 to 1.0 g/kg BW/day steviol. No dose-related teratogenesis was detected. From the result of the present study concerning maternal toxic condition and embryotoxicity, an oral dose of 0.25 g steviol/kg BW/day is regarded as having no observable effect. This steviol-treated dose is derived from stevioside 625 mg/kg BW/day which is approximately 80 times higher than the suggested acceptable daily intake of stevioside for humans (7.938 mg/kg BW/day).

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Cricetinae; Diterpenes; Diterpenes, Kaurane; Dose-Response Relationship, Drug; Embryonic and Fetal Development; Female; Fetal Viability; Gestational Age; Glucosides; Pregnancy; Sweetening Agents; Terpenes; Weight Gain

Teratogenicity of stevioside was examined in rats. Stevioside dissolved in distilled water was given to pregnant Wistar rats by gavage once a day from day 6 through 15 of pregnancy at doses of 0, 250, 500 and 1000 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined for malformation. Stevioside caused no increased incidences of fetal malformation, and no toxic signs in the pregnant rats and the fetuses. It was concluded that stevioside has no teratogenicity in rats when given by gavage. The no observable adverse effect level was estimated to be over 1000 mg/kg/day for both pregnant rats and rat fetuses.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Diterpenes; Diterpenes, Kaurane; Female; Fetus; Glucosides; Male; Pregnancy; Rats; Rats, Wistar; Sweetening Agents; Terpenes