Safety evaluation of certain food additives - ipcs inchem

STEVIOL GLYCOSIDES (addendum) 195
Table 2 (contd)
Test system Test object Substance Concentration Results Reference
Micronucleus Mouse bone
marrow cells
Comet Wistar rat liver,
brain, blood
and spleen
cells
One other study was available on steviol-related material of unspecified
composition, for which the administered dose of steviol could not be identified (Oh
et al., 1999).
2.2.5 Reproductive toxicity
Steviol (90%
purity)
Stevioside
(88.62%
purity)
S9, 9000 × g supernatant from rat liver.
(a) Multigeneration reproductive toxicity
8 g/kg bw Negative Temcharoen et
al. (2000)
4 mg/ml, oral
route
Positive Nunes et al.
(2007)
Stevioside (purity 93–95%) was used to study the effects on reproduction
in groups of 10 female and 5 male Sprague-Dawley rats. The stevioside material
was administered in the diet at a concentration of 0.15%, providing doses equal to
33 mg/kg bw per day for males and 40 mg/kg bw per day for females expressed
as steviol. After 21 days, the animals were allowed to mate. Pregnancy was confirmed
by vaginal plug. During pregnancy, all the animals were fed control diet.
Throughout treatment and pregnancy, animals were observed and weighed regularly,
and their food consumption was measured. Twenty days after the confirmation
of pregnancy, a laparotomy was performed in half of the animals, and the remainder
were allowed to give birth naturally. Animals given a laparotomy were examined for
fetal absorption, death, dimensions and weight. For animals allowed to give birth
naturally, the number of pups and their weight and condition were recorded. The
adults and offspring of all groups showed no adverse effects, no variations in weight
or food consumption, and no difference in pregnancy ratio between the test and
control groups (Akashi & Yokoyama, 1975).
In a preliminary dose-finding study, three groups of six lactating female
HsdRcc Han Wistar rats housed with their litters received a diet containing 0,
25 000, 37 500 or 50 000 mg rebaudioside A (97% purity)/kg from day 14 to day 21
of lactation (with mean doses on days 14–17 of lactation equal to 0, 4711, 8021 and
9484 mg/kg bw per day and on days 18–20 of lactation equal to 0, 6291, 10 045
and 11 386 mg/kg bw per day). The mean doses expressed as steviol in each of
the groups for days 14–17 of lactation were 0, 1551, 2641 and 3123 mg/kg bw per
day and on days 18–20 of lactation were 0, 2072, 3308 and 3749 mg/kg bw per day.
This study was carried out in compliance with GLP and OECD guidelines. Animals
were observed for evidence of ill health twice daily, with a more detailed examination
being carried out weekly on all F0 and selected F1 juvenile rats. Dams were weighed