Joint Expert Committee on Food Additives safety evaluation report on stevioside  Chinese translation (English text extracted from the WHO Technical Report Series 891) Stevia (stevioside) is a two-derivative steviol (steviol: ent-13-hydroxykaur-16-en- 18-oic acid) of sugar, is a composite plant stevia (Stevia rebaudiana Bertoni) natural ingredients. Prior to this, FAO / WHO Joint Expert Committee on Food Additives (the Commission) did not assess the stevioside.

       After feeding rats, stevioside, and will not immediately be absorbed in the small intestine, but the first ligand hydrolysis (aglycone) - steviol, was the intestinal absorption. Steviol was completely absorbed into conjugates excreted in the juice, only a very slight amount detected in the urine. The juice, after discharge, steviol conjugates are hydrolyzed and participate in enterohepatic circulation, its half-discharge period of 24 hours. So far, the only steviol can be detected in the fecal metabolite of stevioside, the discharge of manure is a major way. After intravenous injection, stevioside distributed throughout the body quickly, in part through the tubular secretion, the urine excreted.

Conducted using rat tissues in vitro testing has shown that high concentrations of stevioside to change a number of biochemical parameters. Slight inhibition of oxidative phosphorylation stevioside; and the ability to inhibit steviol is about three times stronger. This inhibitory effect, most likely suppress the mitochondrial adenine nucleotide translocation caused. In addition, steviol also reduce the intestinal mucosa by ATP content, inhibited the ability of intestinal absorption of glucose. Stevioside is the calcium antagonists, can cause low blood pressure, urine and urinary sodium excretion, and reduces the ability of tubular re-absorption of glucose. However, stevioside is not necessarily able to penetrate cell membranes. Although the above findings, mostly based on intravenous injection into mice after the stevioside obtained, but the extract of stevia to rats fed, they could see a similar effect (increase in blood pressure and urine).

Very low acute oral toxicity of stevioside. Rats daily oral concentration in the diet containing 25 grams per kilogram (2.5%) of stevioside  two years later (which is equivalent to body weight per day and men taking taking 970 mg per kilogram of body weight; women taking 1 100 mg), and no significant effect. When the concentration of oral diet containing 50 grams per kilogram (5%), the rats weight gain and survival rate will be reduced. There is no long-term studies show stevia can cause cancer; and the other biometric there is no evidence of tumor Stevia may promote the bladder.

Reproductive toxicity study of stevioside, hamsters daily doses of up to 2 500 mg per kilogram of body weight or per kilogram of body weight in rats daily doses of 3000 mg of stevioside, on their reproductive capabilities are not affected. Studies have shown that female rats given oral administration of stevia instilled agent, can lead to a serious decline in reproductive capacity and long lasting, however, the contraceptive effect is likely nothing to do with stevioside. The tube feeding method of feeding the rats a daily amount of up to 1 000 mg per kilogram of body weight of stevioside, is not teratogenic or embryo poisoning.

Stevioside in vitro a number of animal genetic toxicity tests, the results always showed negative reaction.
In hamsters, with the base - the toxicity of steviol, stevioside more intense, but this phenomenon did not occur in the rat body. After metabolic activation of steviol, the gene was toxic, can cause bacteria to produce forward mutation, and to Chinese hamster lung fibroblast cells to produce gene mutations and chromosomal aberrations. A number of physiological function studies have shown that the characteristics of the structure revealed mutations in the location of steviol hydroxyl group of C13, C16 and C17 as well as links to the unsaturated chain of carbon atoms. Stevioside in the C13 position was glycosylated, there is no reason for causing mutations. Currently, there is no ability to identify mutations caused by the active metabolite of steviol. Some data indicate that the metabolic activation of steviol in the process, the epoxidation may be involved, but other data show that the active metabolite of steviol epoxide is not. Preliminary data showed that steviol may be by activation of human liver microsomes into metabolites cause mutations.

The Committee found that the data on stevioside has many deficiencies. In several studies, the use of laboratory materials (stevioside or steviol) lack of norms or the quality varies, and laboratory materials contain information on other components or contaminants are lacking. In addition, there is no study of stevioside or steviol in the human body's metabolism. Furthermore, the Committee  stevioside in hamsters only long-term toxicity and carcinogenicity data. Steviol teratogenic capacity of in vitro only in animals made fully tested.

The lack of detailed specification information on stevia, but also a number of the existing lack of toxicity data, the Commission can not be used to study the toxicity of commercial products, they can not determine the allowable daily intake of stevioside (ADI).

Re-assessment of stevioside, the Commission considers it necessary for the formulation of the nature of stevioside standard, to ensure that the material tested to represent the relevant goods. In addition, the Commission also need to test things on the nature of the data, the metabolism of stevioside in the body of data, and steviol in the appropriate genetic toxicity in vivo studies.

The Committee prepared a special report on toxicity. Because information is not available and therefore can not write a description of the nature of stevioside . (Food and Environmental Hygiene Department has been the World Health Organization to allow translation of the English text of the report in Chinese and published in the department's website, the Food and Environmental Hygiene Department would like to thank the World Health Organization.)