Az alábbiakban az EFSA (European Food Safety Authority, azaz Európai Élelmiszer-biztonsági Hivatalatóság) néhány stevia növényekkel, illetve azok hatóanyagával kapcsolatos vizsgálatának összefoglalóját olvashatják.

 

Az eredeti cikkek a szervezet honlapján elérhetők: www.efsa.europa.eu.

 

 

Scientific Opinion on the safety of steviol glycosides for the proposed uses as a food additive

 

Summary

Following a request from the European Commission, the Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on the safety of steviol glycosides as a sweetener for use in the food categories specified in the dossiers from the three petitioners.

The steviol glycosides produced by the three petitioners are chemically defined mixtures that comprise not less than 95% stevioside and/or rebaudioside A. Stevioside and/or rebaudioside A are more than 95% of the mixture in two of the products. In the third product, rebaudioside A is the major component of the mixture (? 95%) together with other glycosides. In addition, smaller amounts of rebaudiosides B, C, D, E and F, steviolbioside, rubusoside and dulcoside A are present in the final mixtures, as indicated by the petitioners.

The three petitioners proposed that the specifications for the steviol glycosides should comply with the specifications adopted by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) at the 69th meeting.

The petitioners indicated that all manufacturers use the same basic steps to extract steviol glycosides from the leaves of the Stevia rebaudiana Bertoni plant, although there is some variation in the later stages of purification and separation of the glycosides. Steviol glycosides can be identified in foods and beverages by High Performance Liquid Chromatography (HPLC) methods.

Different studies assessed the bulk stability of dry steviol glycosides under various storage conditions and in food matrices over a range of pH values, processing conditions, at both room temperature and elevated temperatures. The photostability of the preparation was examined under dry and aqueous conditions. The Panel notes that in these experiments the extent of degradation of the tested steviol glycoside (rebaudioside A) that occurred ranged from a few percent up to 63% under different storage (pH and temperature) and food production conditions. The Panel notes that in presence of high temperatures (e.g. heating, baking) substantial degradation of steviol glycosides might take place.

Stevioside as a sweetener was evaluated by the Scientific Committee for Food (SCF) in 1984, 1989 and 1999. The SCF concluded that the use of stevioside was “toxicologically not acceptable” due to insufficient available data to assess its safety.

JECFA reviewed the safety of steviol glycosides (in 2000, 2005, 2006, 2007, and 2009) and established an ADI for steviol glycosides (expressed as steviol equivalents) of 4 mg/kg bw/day.

The Panel evaluated oral animal studies of metabolism and toxicokinetics, laboratory animal toxicity studies, in vitro and in vivo genotoxicity studies, and human studies with single or repeated administration of steviol glycosides.

Metabolic studies with steviol glycosides in animasl and humans demonstrated that intact steviol glycosides are poorly absorbed after oral exposure but that they are hydrolysed by the microflora in the colon to steviol. A large amount of steviol is absorbed; the rest is excreted in the faeces. In the liver, steviol undergoes conjugation with glucuronic acid to form steviol glucuronide. The only inter-species difference is that the glucuronide is excreted primarily via the urine in humans and via the bile in rats. No accumulation of steviol glycoside derivatives occurs in the body. Besides steviol glucuronide, no other derivatives could be detected in the urine of humans exposed orally to steviol glycosides.

Rebaudioside A and stevioside both show similar pharmacokinetics in the rat. In humans, rebaudioside A and stevioside are also metabolised and excreted by similar pathways. Therefore, the Panel considers the results of toxicological studies on either stevioside or rebaudioside A applicable for the safety assessment of steviol glycosides in general.

In some subchronic and carcinogenicity studies, and also in the 2-generation reproductive toxicity study body weight gains were lower in the treated groups compared to the controls. In these studies decreases in feed consumption and in feed conversion efficiency were recorded. The Panel considers the effects on body weight as not adverse or indicative of toxicity but related to lower palatability and lower nutritional value of feed containing the steviol glycosides. Therefore body weight parameters are not considered to be appropriate endpoints for setting No-Observed-Adverse-Effect Levels (NOAELs) for these studies.

Overall, stevioside and rebaudioside A do not show evidence of genotoxicity in vitro or in vivo. Although a single Comet assay was reported to show effects indicative of DNA damage, the Panel considers that this study does not provide substantive evidence of a genotoxic potential for stevioside, given methodological concerns and also the fact that similar findings were not seen in earlier studies in mice using steviosides of higher or lower purities. The Panel notes that steviol and some of its oxidative derivates show clear evidence of genotoxicity in vitro, particularly in the presence of a metabolic activation system. However, studies of DNA damage and micronucleus formation in rats, mice and hamsters have shown that the genotoxicity of steviol is not expressed in vivo at doses of up to 8000 mg/kg bw. Given that the available toxicokinetic data indicate that free steviol is absent from the systemic circulation in humans or, at worst, present at very low (negligible) levels, any concern raised by the in vitro genotoxicity profile of steviol is fully addressed by the fact that the genotoxic potential of steviol is not expressed in vivo, and by the negative genotoxicity findings for steviol glycosides in vitro and in vivo.

The results of toxicological testing indicated that steviol glycosides are not genotoxic, carcinogenic, nor associated with any reproductive/developmental toxicity. The NOAEL in the 2-year carcinogenicity study in the rat was 2.5% stevioside (95.6% purity) equal to 967 mg stevioside/kg bw/day (corresponding to approximately 388 mg steviol equivalents/kg bw/day).

Single doses of 1000 mg steviol glycosides/person/day (97% rebaudioside A) (corresponding to approximately 330 mg steviol equivalents/day) did not affect glucose homeostasis and did not affect blood pressure in individuals with normal glucose tolerance or type-2 diabetes mellitus. Also repeated use for 16 weeks of 1000 mg rebaudioside A/person/day did not alter glucose homeostasis in individuals with type-2 diabetes mellitus. Blood pressure parameters were not significantly affected by oral intake of 1000 mg rebaudioside A/person/day for 4 weeks in individuals with normal and low systolic blood pressure. This daily dose corresponds to 16.6 mg of rebaudioside A/kg bw for a person weighing 60 kg and to approximately 5.5 mg steviol equivalents/kg bw/day.

Available data concerning anaphylaxis-like reactions by stevioside in children with atopic eczema do not, according to the Panel, raise concern regarding the potential for oral exposure to steviol glycosides to trigger anaphylactic reactions. Sparse in vitro and in vivo data indicate that stevioside may have immunostimulating effects and modulatory activities on inflammation. The Panel considered that immunostimulating and immunomodulating effects of steviol glycosides in cell lines and rodent models have not been demonstrated in a robust and reproducible way, which could enable them to be used as pivotal studies for risk assessment. However, these observations deserve more in-depth examination as, if they are confirmed, they may raise concern regarding the use of steviosides in some sub-groups of the population, particularly for individuals suffering from auto-immune diseases or inflammation of the gastrointestinal tract.

When considering the proposed maximum use levels (Tier 2), the mean dietary exposure to steviol glycosides expressed as steviol equivalents in European children (aged 1-14 years) ranged from 0.7 to 7.2 mg/kg bw/day, and from 3.3 to 17.2 mg/kg bw/day at the 95th percentile. The main contributors (>10% in all countries) to the total anticipated exposure to steviol glycosides, expressed as steviol equivalents, are soft drinks (11 to 58%) and desserts, including flavoured milk products (14 to 71%). Confectionery accounted for 11% of exposure in two countries. Dried potato granules and flakes and candied fruits and vegetables, mostardo di frutta accounted for 17 and 18% of exposure in one country.

Estimates reported for the UK adult population give a mean dietary exposure to steviol glycosides, expressed as steviol equivalents of 2.2-2.7 mg/kg bw/day and of 8.0-9.7 mg/kg bw/day for high level exposures (97.5th percentile). The main contributors to the total anticipated exposure to steviol glycosides expressed as steviol equivalents (>10 %) are soft drinks (37%) and beer, cider and perry (33%).

After considering all the data on stability, degradation products, metabolism and toxicology, the Panel establishes an Acceptable Daily Intake (ADI) for steviol glycosides, expressed as steviol equivalents, of 4 mg/kg bw/day based on application of a 100-fold uncertainty factor to the NOAEL for stevioside of 967 mg stevioside/kg bw/day (corresponding to approximately 388 mg steviol equivalents/kg bw/day) from a 2-year carcinogenicity study in the rat.

Conservative estimates of steviol glycosides exposures both in adults and in children suggest that it is likely that the ADI would be exceeded at the maximum use levels proposed by the petitioners.

 

Published: 14 April 2010



 

 

EFSA revises assessment of consumer exposure to steviol glycosides

 

News Story, 26 January 2011

 

The European Food Safety Authority (EFSA) has reviewed its previous assessment of consumer exposure to the sweeteners steviol glycosides[1] based on the revised levels of use proposed by the applicants. More commonly referred to as stevia, these sweeteners are proposed for use in sugar-free or reduced energy foods such as certain flavoured drinks and confectionary. Although the revised exposure estimates are slightly lower than those in the opinion adopted by EFSA’s ANS Panel in April 2010, adults and children who are high consumers of foods containing these sweeteners, could still exceed the Acceptable Daily Intake (ADI) established by the Panel if the sweeteners are used at maximum levels[2].

In April 2010, EFSA’s evaluation of the safety and consumer exposure indicated that some adults and children could exceed the ADI of 4 mg per kg body weight per day (mg/kg bw/day) if the sweeteners were used at the maximum use levels proposed by the applicants. The European Commission therefore asked industry to revise the uses proposed for the substances. In order to ensure that the use of such sweeteners would be safe for consumers, the European Commission subsequently requested that EFSA carry out a new exposure assessment on the basis of the revised uses proposed.

Taking into account the revised proposed uses and use levels submitted by industry, EFSA calculated the exposure to steviol glycosides from various food categories including non-alcoholic flavoured drinks which, given food consumption habits, would be among the main sources of exposure to steviol glycosides for both adults and children. In estimating the exposure, EFSA used data from several food consumption databases, including EFSA’s Comprehensive Food Consumption Database.

For high consumers, revised exposure estimates to steviol glycosides remain above the established ADI of 4 mg per kg body weight. For European children (aged 1-14) exposure ranges from 1.7 to 16.3 mg/kg bw/day; and for adults, revised exposure estimates range from 5.6 to 6.8 mg/kg bw/day.

 


 

Scientific Opinion on Flavouring Group Evaluation 310 (FGE.310): Rebaudioside A from chemical group 30

 

Summary


The European Food Safety Authority (EFSA) asked the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (the Panel) to provide scientific advice to the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Panel was requested to evaluate one flavouring substance in the Flavouring Group Evaluation 310, using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. This flavouring substance belongs to chemical group 30, Annex I of the Commission Regulation (EC) No 1565/2000.

The present Flavouring Group Evaluation deals with the steviol glycoside rebaudioside A [FL-no: 16.113].

It has been reported that the flavouring substance occurs naturally in Stevia rebaudiana, up to 16200 – 72700 mg/kg, depending on plant species.

The flavouring substance is included in the specifications for the food additive (sweetener) steviol glycosides which has recently been evaluated by both the JECFA (JECFA, 2009a) and EFSA (EFSA, 2010k). The flavouring substance rebaudioside A [FL-no: 16.113] is closely related structurally to stevioside. Both compounds contain the same aglycon steviol, the only difference being that rebaudioside A contains an extra glucose molecule in the glycoside moiety. Steviol glycosides are chemically defined mixtures that comprise not less than 95 % stevioside and/or rebaudioside A. Both the JECFA and EFSA established an ADI for steviol glycosides (including rebaudioside A), expressed as steviol equivalents, of 4 mg/kg bw/day.

In its evaluation, the Panel as a default used the “Maximised Survey-derived Daily Intake” (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavouring Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the Industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach.

In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a “modified Theoretical Added Maximum Daily Intake” (mTAMDI) approach based on the normal use levels reported by Industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Panel requires more precise data on use and use levels.

Overall, stevioside and rebaudioside A do not show evidence of genotoxicity in vitro or in vivo.

Because a comprehensive and adequate toxicological database, including human studies, is available for steviol glycosides the candidate substance rebaudioside A [FL-no: 16.113] should not be evaluated using the Procedure as referred to in the Commission Regulation EC No 1565/2000 (EC, 2000a). Instead the Panel based its evaluation on a comparison of the ADI of 4 mg/kg bw, expressed as steviol, established by EFSA (EFSA, 2010k) with the estimated MSDI and mTAMDI values.

According to the default MSDI approach, the substance has a daily per capita intake as a flavouring of 1200 microgram/capita/day. The MSDI of 1200 microgram rebaudioside A/capita/day, equivalent to 20 microgram rebaudioside A/kg bw/day, for a person weighing 60 kg, corresponding to a daily intake of 6.6 microgram steviol/kg bw/day, using a conversion factor of 0.33 (EFSA, 2010k) for converting the amount of rebaudioside A into steviol equivalents. This intake, as a flavouring substance, amounts to 0.17 % of the ADI of 4 mg/kg bw, expressed as steviol, established by EFSA (EFSA, 2010k). The Panel concluded that rebaudioside A [FL-no: 16.113] does not pose a safety concern when used as flavouring substance at the estimated level of intake, based on the MSDI approach.

The estimated intake of the candidate substance rebaudioside A [FL-no: 16.113] based on the mTAMDI is 10888 microgram/person/day, is equivalent to 181 microgram rebaudioside A/kg bw/day, for a person weighing 60 kg. This correspond to a daily intake of 60 microgram steviol/kg bw/day, using a conversion factor of 0.33 (EFSA, 2010k) for converting the amount of rebaudioside A into steviol equivalents. This intake amounts to 1.5 % of the ADI of 4 mg/kg bw, expressed as steviol, established by EFSA (EFSA, 2010k). The Panel concluded that rebaudioside A [FL-no: 16.113] does not pose a safety concern when used as flavouring substance at the estimated level of intake, based on the mTAMDI approach.

Steviol glycosides are (expected to be) authorised as food additives in the EU. The Panel noted that in its recent evaluation the EFSA ANS Panel estimated the potential exposure to steviol glycosides from use as food additives. When considering the proposed maximum use levels as food additive, the mean dietary exposure to steviol glycosides expressed as steviol equivalents in European children might exceed the ADI of 4 mg/kg bw/day. Thus, the estimated intake of rebaudioside A [FL-no: 16.113] from its use as a flavouring substance contributes to the total intake of steviol glycosides.

In order to determine whether the conclusion for the flavouring substance can be applied to the materials of commerce, it is necessary to consider the available specifications. Adequate specifications including complete purity criteria and identity for the materials of commerce have been provided for the flavouring substance rebaudioside A [FL-no: 16.113].

The Panel concluded that on the basis of the default MSDI approach and the mTAMDI approach, rebaudioside A [FL-no: 16.113] would not give rise to safety concerns at the estimated level of intake arising from its use as flavouring substance.

 

Published: 25 May 2011



 

 

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