The EFSA Journal (2007) 483, 1-6

Transcription

1 The EFSA Journal (2007) 483, 1-6 Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies on a request from the Commission related to a notification from CEPS on whey used in distillates for spirits pursuant to Article 6 paragraph 11 of Directive 2000/13/EC (Request Nº EFSA-Q ) (adopted on 3 May 2007) SUMMARY In addition to the information provided for temporary exemption, the applicant provided further information regarding distillates made from milk-derived whey which include gin, genever, pastis, ouzo, anis, aquavit, vodka, jagertee, advocaat, slivovice and similar spirit drinks. The beverages in question are widely consumed in the European Union. The literature survey that includes information up to April 2006 failed to reveal allergic reactions after consumption of distillates made from whey, although under-reporting cannot be excluded. Further evidence of the unlikelihood of distillates made from whey to elicit allergic reactions stems from additional analytical data on potential residual proteins and their allergenicity in the distillates and the distillation process. The analytical methodology did not address the allergenic activity of residual protein levels in the final products by using appropriate human sera. Neither epidemiological studies nor double-blind placebo-controlled food challenge studies in clinical settings have been carried out to address possible adverse allergic reactions to distilled spirit drinks due to whey allergens. Based on the data submitted by the applicant, the Panel notes that proteins, peptides and lactose are not carried over into the distillate during a properly controlled distillation process, at least not above 0.5 mg/l for proteins and 0.04 mg/l for lactose. The Panel considers that distillates made from whey are unlikely to trigger a severe allergic reaction in susceptible individuals. KEY WORDS Allergenicity, distillates, protein content, whey protein, milk allergy, lactose, betalactoglobulin. Page 1 of 6

2 BACKGROUND In November 2003, the European Parliament and the Council adopted Directive 2003/89/EC 1 amending Directive 2000/13/EC, as regards indication of the ingredients present in foodstuffs. Annex IIIa of the Directive specifies a list of food ingredients or substances that are known to trigger allergic reactions or intolerances in sensitive individuals for which no labelling exemptions are allowed. Whenever the listed ingredients/substances or their derivatives are used in the production of foodstuffs, they must be labelled. Article 1, paragraph 11, subparagraph 2 of the Directive establishes a procedure allowing for temporary labelling exemption of derivatives from ingredients listed in Annex IIIa for which it has been scientifically established that it is not possible for them to cause adverse reactions. In accordance with this provision, submissions of requests for temporary labelling exemption were notified to the Commission before 25 August The Commission, after consultation with the European Food Safety Authority, adopted a list (Directive 2005/26/EC 2 ) of those ingredients which are temporarily excluded from Annex IIIa until 25 November 2007, pending the final results of the notified studies. Consequently, applicants who submitted a dossier in 2004 on the basis of subparagraph 2, resulting in the inclusion of a product in the list of Directive 2005/26/EC, and who are seeking exclusion of that product from Annex IIIa beyond 25 November 2007 will have to submit a request enclosing the final results of the notified scientific studies. Therefore in the context of the permanent labelling exemption procedure, the European Food Safety Authority is asked to provide scientific opinions on the submissions in accordance with the present terms of reference. TERMS OF REFERENCE In accordance with Article 29 (1) (a) of Regulation (EC) N 178/2002, the European Commission requests the European Food Safety Authority to evaluate the scientific data submitted by the European Spirits Organisation (CEPS) in the framework of the procedure laid down in Article 6, paragraph 11 of Directive 2000/13/EC. On the basis of that evaluation, EFSA is requested to issue an opinion on the information provided, and particularly to consider the likelihood of adverse reactions triggered in susceptible individuals by the consumption of the following ingredients/substances used under the conditions specified by the applicant: whey used in distillates for spirits. ASSESSMENT Taking account of the potential allergen content and the well documented clinical allergic reaction in individuals sensitive to the stated material (whey/milk) (NDA, 2004a), it is 1 Directive 2003/89/EC of the European Parliament and of the Council amending Directive 2000/13/EC as regards indication of the ingredients present in foodstuffs. OJ L , p Commission Directive 2005/26/EC of 21 March 2005 establishing a list of food ingredients or substances provisionally excluded from Annex IIIa of Directive 2000/13/EC of the European Parliament and of the Council. OJ L 75, , p Page 2 of 6

3 appropriate for the Panel to assess the likelihood that the finished product may cause a reaction in a milk (whey) allergic consumer. In 2004, the Panel issued an Opinion on a notification submitted by the European Spirits Organisation (CEPS) to the European Commission pursuant to Article 6, paragraph 11 of Directive 2000/13/EC as amended by Directive 2003/89/EC, for temporary exemption from labelling (NDA, 2004b). Under the framework of permanent exemption from labelling, the present Opinion is based on the assessment of an updated dossier from CEPS, which contains additional information or data mainly with regard to literature review and laboratory-based in vitro tests. 1. Manufacturing process Distillates made from whey include gin, genever, pastis, ouzo, anis, aquavit, vodka, jagertee, advocaat, slivovice and similar spirit drinks. The steps involved in production of whey-based distillates comprise whey processing (i.e. extraction of whey proteins from cheese whey by ultrafiltration, leaving the lactose containing permeate suitable for fermentation), fermentation (conversion of lactose to alcohol by action of yeast), distillation (concentration of alcohol, removal of non-volatiles, control of flavour) and post-distillation processes (flavouring, maturation). A continuous distillation process employing multiple column stills is used. A properly controlled process should make it unlikely that significant levels of non-volatile, high boiling point compounds are carried over into the distillate. In relation to alcoholic distillate production, this would include proteins, peptides, amino acids, and saccharides. No studies presented in the open literature provided evidence that proteins and lactose do have a vapour pressure and there is general agreement in the scientific community that they do not distil. To support the distillation concepts, model distillations of proteins (bovine serum albumin (BSA) and bovine beta-lactoglobulin (BLG)) and lactose were conducted by the applicant. No BSA, nor BLG, nor lactose were detected in the distillates collected above the limit of detection (LOD) of 0.5 mg/l, 0.5mg/L and 0.01mg/L, respectively. However, the distillation of pure protein solutions in the laboratory, without the presence of additional components typically found in industrial distillation matrices, can result in different foaming, boiling homogeneity, steam carry over, and do not necessarily represent the industrial conditions. 2. Evidence of non-allergenicity 2.1 History of non-allergenicity of the product The applicant performed a literature survey that includes information up to April 2006, to find links between milk (whey) allergy or lactose intolerance and the consumption of spirit drinks. This review was undertaken using the PubMed database of the US National Library of Medicine. Titles and abstracts were searched for MILK or WHEY ALLERGY and this gave a number of literature reports (1384 and 65 respectively). Linking of these search terms with specific alcoholic beverages (GIN or VODKA) and with DISTILLED SPIRITS identified no reported literature. Use of the more general term ALCOHOL with MILK ALLERGY yielded four literature reports, three of which referred to papers on general food allergies and one to the preparation of an alcohol soluble extract. Combination of ALCOHOL with WHEY ALLERGY yielded no published reports. Replacing MILK or WHEY ALLERGY in the above searches Page 3 of 6

4 with LACTOSE INTOLERANCE produced only three results, for the combination with ALCOHOL. None of the three reports specifically deal with lactose intolerance or make any connection with alcohol based products. Combination of ALLERG* and DISTILLED SPIRITS identified one reference which was a review of allergic and asthmatic reactions to alcoholic drinks (Vally and Thompson, 2003). From this review sensitivities to alcoholic drinks do not appear to be immune mediated, but are more frequently pharmacological intolerances to specific chemicals in these drinks. Where allergic and asthmatic reactions to specific non-alcohol components have been reported, these are almost wholly concerned with non-distilled drinks. Only one reported investigation of spirit consumption triggering asthmatic attacks could be found, however the substance causing the reaction was not identified (Breslin et al., 1973). Patients reacted to specific drinks but not to the equivalent amount of ethanol. Skin prick tests for routine common allergens gave no reaction to milk. The applicant s literature search did not reveal allergic or lactose intolerance reactions after consumption of distillates made from whey used before distillation. It remains possible that adverse effects due to drinking of distillates made from whey used before distillation may not be perceived as due to whey derived proteins but rather be attributed to alcohol, and underreporting may thus have occurred. The Panel notes that sales of spirit drinks in the European Union totalled over 260 million cases of 12 bottles of 700 ml each Laboratory-based tests In vitro studies The applicant asserts that the physico-chemical properties of the allergenic materials of whey (proteins, polypeptides) and lactose will result in their complete lack of volatility, and hence their absence from products obtained by distillation. The applicant supports this assertion with information from the scientific literature. The analytical study submitted by the applicant includes 24 samples of neutral spirits produced by two companies, covering three distillery sites. The applicant used an improved method for total protein detection: the Bradford Analysis Microassay. The method was calibrated with BSA down to a concentration of 0.6 mg/l. As it was seen that the presence of alcohol interfered with the analysis, samples were evaporated to dryness and reconstituted in water. Appropriate calibration curves were constructed with BSA as a protein standard. The limit of detection (LOD) was 0.5 mg/l taking into account a good recovery ratio. No protein was detected in any of the industrial distillate samples analysed in the extended survey above 0.5 mg/l. The method utilised is highly influenced by colour and therefore can be applied only to uncoloured spirits. In order to determine the presence of BLG in the distillates, a specific commercial whey protein (beta-lactoglobulin) enzyme-linked immunosorbent assay (ELISA) was used following a previous concentration step. The method was validated for a LOD of 0.5 mg/l with native BLG. No BLG was detected in any of the 24 whey derived alcohol distillates by the ELISA assay above 0.5 mg/l. However, although, according to the assay kit instructions the assay Page 4 of 6

5 detects native and processed proteins and fragments thereof, no evidence is provided that the kit is able to detect denatured BLG. A specific lactose determination was carried out by ion chromatography HPLC/amperometric detection with a LOD of 0.01mg/L. Out of the 24 industrial samples analysed, lactose was not detected in 20 of the samples. Four samples produced positive results in the range of 0.02 mg/l to mg/l. If considering the proper dilution to adjust the alcoholic strength (about 40% alcohol by volume), the result would equate to mg/l-0.04mg/l lactose. At the request of EFSA, the applicant has further addressed these findings, and identified a possible route of contamination of the samples, comprising the use of four samples that were not specifically taken for the purpose of their study, but from routinely stored samples using bottles of unknown provenance. The analytical data presented indicate that whey proteins, peptides and lactose are not transported into the products of distillation during spirit manufacturing, at least not above 0.5 mg/l for proteins and 0.04 mg/l for lactose. The analytical methodology did not address the allergenic activity of residual protein levels in the final products by using appropriate human sera Animal studies No animal studies were provided or referred to in the data submitted. 2.3 Clinical studies Skin tests No systematic skin prick testing studies in allergic individuals exposed to distillates have been reported. Only one case report of spirit consumption triggering asthmatic attacks could be found. However, the substance causing the reaction was not identified (Breslin et al., 1973). Skin prick tests for routine common allergens gave no reaction to whey. Hence, this case report does not indicate involvement of whey allergens in the responses noted Double blind placebo controlled food challenge (DBPCFC) No DBPCFC data in whey allergic individuals exposed to distillates made from whey used before distillation have been reported Epidemiological studies The applicant has not carried out epidemiological studies in order to investigate possible adverse reactions to distilled spirit drinks due to whey. CONCLUSIONS Based on the data submitted by the applicant, the Panel notes that proteins, peptides and lactose are not carried over into the distillate during a properly controlled distillation process, at least not above 0.5 mg/l for proteins and 0.04 mg/l for lactose. The Panel considers that distillates made from whey are unlikely to trigger a severe allergic reaction in susceptible individuals. Page 5 of 6

6 DOCUMENTATION PROVIDED TO EFSA Dossier submitted by the European Spirits Organisation (CEPS) to the European Commission pursuant to Article 6, paragraph 11 of Directive 2000/13/EC on 25 August REFERENCES Breslin ABX, Hendrick DJ, Pepys J (1973). Effect of disodium cromoglycate on asthmatic reactions to alcoholic beverages. Clin Allergy 3: NDA (Scientific Panel on Dietetic Products, Nutrition and Allergies) (2004a). Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies on a request from the Commission relating to the evaluation of allergenic foods for labelling purposes. The EFSA Journal 32, NDA (Scientific Panel on Dietetic Products, Nutrition and Allergies) (2004b). Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies related to a notification from CEPS on distillates made from whey pursuant to Article 6, paragraph 11 of Directive 2000/13/EC. The EFSA Journal 131, Vally H and Thompson PJ (2003). Invited Review: Allergic and asthmatic reactions to alcoholic drinks. Addiction Biology 8: PANEL MEMBERS Jean-Louis Bresson, Albert Flynn, Marina Heinonen, Karin Hulshof, Hannu Korhonen, Pagona Lagiou, Martinus Løvik, Rosangela Marchelli, Ambroise Martin, Bevan Moseley, Andreu Palou, Hildegard Przyrembel, Seppo Salminen, John (Sean) J Strain, Stephan Strobel, Inge Tetens, Henk van den Berg, Hendrik van Loveren and Hans Verhagen. ACKNOWLEDGEMENT The Scientific Panel on Dietetic Products, Nutrition and Allergies wishes to thank Taraneh Dean, Martin Stern and Jean-Michel Wal for their contributions to the draft opinion. Page 6 of 6