The acute toxicity of stevioside and steviol (a product of enzymatic hydrolysis of stevioside) was investigated in three animal species including rat, mouse and hamster. The susceptibility to stevioside and steviol acute toxicity in both sexes of these animal species was compared. The animals were treated intragastrically with stevioside or steviol and general signs and symptoms were observed. The numbers of dead animals were recorded within a period of 14 days after administration for estimation of LD50. Stevioside at a dose as high as 15 g/kg BW was not lethal to either mice, rats or hamsters. Hamsters were found to be more susceptible to steviol than rats or mice. LD50 values of steviol in hamsters were 5.20 and 6.10 g/kg BW for males and females, respectively. In rats and mice, LD50 values of steviol were higher than 15 g/kg BW in both sexes. Histopathological examination in the kidney of hamsters induced by steviol revealed severe degeneration of the proximal tubular cells. These structural alterations were correlated with the increases in serum blood urea nitrogen (BUN) and creatinine. Therefore, the possible cause of death induced by steviol might be due to acute renal failure.

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).

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The toxic and mutagenic effects of gamma‐irradiated peanut meal contaminated with aflatoxin B1 were studied in Salmonella typhimu‐rium strain TM 677, using forward mutation to 8‐azaguanine resistance. After treatment with 5 to 10 M‐rad gamma radiation, the contaminated peanut meal lost its toxic and mutagenic properties. Irradiation at 0.1 to 1.0 M‐rad removed 75–100% of the toxicity but not mutagenicity.