Safety evaluation of certain food additives - ipcs inchem

STEVIOL GLYCOSIDES (addendum) 189
al., 2004a, 2006). Stevioside was found to stimulate secretion of insulin in pancreatic
islets isolated from NMRI mice with no evidence of desensitization of the -cells
observed over time; in combination with glucagon-like peptide-1, stevioside was
found to counteract the desensitization of pancreatic cells induced by the diabetes
drug glyburide (Chen et al., 2006a, 2006b).
In a study in which isosteviol (99.8% purity) was incubated with rat aortic
smooth muscle cells (0.01–10 μmol/l) and a range of cardioactive drugs
(vasopressin, phenylaphrine, apamin, glibenclamide, 4-aminopyridine and
charybdotoxin), the intracellular calcium concentration was lowered by isosteviol,
which was mediated through the small-conductance calcium-activated potassium
channels and voltage-gated channels as well as the adenosine triphosphate (ATP)–
sensitive potassium channels. Large-conductance calcium-activated potassium
channels did not mediate the action of steviol (Wong et al., 2004b).
Stevioside has the potential to regulate acetyl-coenzyme A carboxylase
(ACC) and subsequently may have a role in protecting the function of pancreatic
-cells when exposed to high levels of glucose (Chen et al., 2007).
Stevioside was found to inhibit absorption of glucose by up to 40% in rat
duodenum at levels of 0.8 mg/ml (Maier et al., 2003).
Stevioside (98% purity) increased the production of proinflammatory
cytokines tumour necrosis factor-alpha (TNF-) and interleukin-1beta (IL-1) at a
concentration of 1 mmol/l and induced nitric oxide production at 0.1 and 1.0 mmol/l
in unstimulated THP-1 cells. In lipopolysaccharide-stimulated THP-1 cells,
stevioside (1 mmol/l) reduced the release of TNF- and IL-1 and had no effect on
nitric oxide production. The authors concluded that stevioside could have an antiinflammatory
role and that its TNF- and nitric oxide stimulatory properties may form
a basis to reports of anti-tumour-promoting effects (Boonkaewwan et al., 2006).
A number of other studies were available on steviol-related material of
unspecified composition, for which the administered dose of steviol could not be
identified (Pezzuto, 1986; Chatsudthipong & Thongouppakarn, 1995;
Chatsudthipong & Jutabha, 2001; Chatsudthipong et al., 2003; Nakamura et al.,
2003; Srimaroeng et al., 2005a, 2005b; Chen et al., 2006c; Hong et al., 2006;
Ghanta et al., 2007).
2.2 Toxicological studies
2.2.1 Acute toxicity
Studies on the acute toxicity of steviol glycosides and related substances are
summarized in Table 1.
A number of other studies were available on steviol-related material of
unspecified composition, for which the administered dose of steviol could not be
identified (Pomaret & Lavieille, 1931; Lee et al., 1979).