Summary of estimates of exposure to steviol glycosides (as steviol)
 

ª WHO Global Environment Monitoring System — Food Contamination Monitoring and Assessment Programme
ь These estimates were prepared in parallel to those for the international estimates; it was assumed that all dietary sugars in diets in Japan and the USA would be replaced by steviol glycosides on a sweetness equivalent basis, at a ratio of 200 :1

Evaluation

The Committee noted that most of the data requested at its fifty-first meeting, e.g. data on the metabolism of stevioside in humans, and on the activity of steviol in suitable studies of genotoxicity in vivo, had
been made available. 

The Committee concluded that stevioside and rebaudioside A are not genotoxic in vitro or in vivo and that the genotoxicity of steviol and some of its oxidative derivatives in vitro is not expressed in vivo. The
NOEL for stevioside was 970mg/kgbw per day in a long-term study evaluated by the Committee at its fifty-first meeting.

The Committee noted that stevioside has shown some evidence of pharmacological effects in patients with hypertension or with type-2 diabetes at doses corresponding to about 12.5–25mg/kgbw per day
(equivalent to 5–10mg/kgbw per day expressed as steviol). The evidence available at present was inadequate to assess whether these pharmacological effects would also occur at lower levels of dietary
exposure, which could lead to adverse effects in some individuals (e.g. those with hypotension or diabetes). The Committee therefore decided to allocate a temporary ADI, pending submission of further
data on the pharmacological effects of steviol glycosides in humans.

A temporary ADI of 0–2mg/kgbw was established for steviol glycosides, expressed as steviol, on the basis of the NOEL for stevioside of 970mg/kgbw per day (or 383mg/kgbw per day, expressed as steviol)
in the 2-year study in rats and a safety factor of 200. This safety factor incorporates a factor of 100 for inter- and intra-species differences and an additional factor of 2 because of the need for further information.
The Committee noted that this temporary ADI only applies to products complying with the specifications.
The Committee required additional information, to be provided by 2007, on the pharmacological effects of steviol glycosides in humans.

These studies should involve repeated exposure to dietary and therapeutic doses, in normotensive and hypotensive individuals and in insulin-dependent and insulin-independent diabetics.

A toxicological monograph was prepared, incorporating summaries of the key toxicological data on the evaluation of stevioside conducted by the Committee at its fifty-first meeting.
New tentative specifications were prepared, accompanied by a Chemical and Technical Assessment. In order to be able to remove the tentative designation from the specifications, the following further information for commercially available products was required by 2007: