Developmental Toxicity of Steviol, a Metabolite of Stevioside, in the Hamster

Abstract

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).

Occurrence, Biological Activities and Synthesis of Kaurane Diterpenes and their Glycosides

“…Although some work has failed to demonstrate carcinogenic, teratogenic, mutagenic or toxic actions of stevioside (78), after oral administration to rats [108][109][110][111], at doses up to 1.2 % of the diet, and considering, therefore, a maximum ingestion recommendable of 7.94 mg·kg -1 ·d -1 for the human organism [112], others have demonstrated that steviol (24), an aglycone obtained from complete hydrolysis of stevioside, showed a high toxicity in pregnant females and embryos of hamsters, at doses of 0.75 and 1.00 mg·kg -1 ·d -1 , administered from 6 th to 10 th day of gestation [112][113][114]. The animals treated with these doses showed acute renal failure, embryotoxic effects such as weight loss and retardation of the process of fetal ossification, and death.…”

Stevia : A True Glycoside Used as a Sweetener and Not Affecting Behavior

“…A metabolite of steviosides is steviol. Working on pregnant hamsters intubated with steviol, Wasuntarawat et al 34 found that doses of 0.75 g and 1.0 g/kg/day were toxic for dams and fetuses, while a dose of 0.25 gr/kg/day of steviol was not. Such a dose correspond to 625 mg/kg/day of stevioside, what is about 80 times more than the dose usually recommended for humans (7.9 mg x 80 = 632 mg).…”

Stevia rebaudianaBertoni. Un potencial adyuvante en el tratamiento de la diabetes mellitus

“…Un estudio publicó disminución en el ritmo de nacimiento de ratas tratadas con esteviósido (Planas & Kucacute, 1968) lo que aumentó la preocupación sobre los posibles efectos sobre la fertilidad y teratogénesis; sin embargo estos resultados no pudieron ser reproducidos (Shiotsu, 1996), y por el contrario varios estudios en animales han demostrado que el esteviósido vía oral no tiene efecto sobre la fertilidad en roedores (Akashi & Yokoyama, 1975;Wasuntarawat et al, 1998;Yodyingyuad & Bunyawong, 1991).…”