Statement on the safety assessment of the exposure to lutein preparations based on new data on the use levels of lutein 1

EFSA Journal 2012;10(3):2589 SCIENTIFIC OPINION Statement on the safety assessment of the exposure to lutein preparations based on new data on the use levels of lutein 1 EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) 2, 3 European Food Safety Authority (EFSA), Parma, Italy ABSTRACT Following a request by EFSA, the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) carried out a new exposure assessment of lutein (E 161b) as a food colour, based on corrected data provided by the food industry. In 2010 the ANS Panel estimated at Tier 3 the exposure to lutein as food colour to exceed the ADI of 1 mg/kg bw/day at the upper end of the range. In 2011, industry provided EFSA with corrected use levels of lutein. The Panel considered that the new use levels are significantly lower than the ones provided previously and thus would have an important impact on Tier 3 exposure estimates. The new Tier 3 estimates result in an exposure to lutein of European adults of 0.1 mg/kg bw/day at the mean and of 0.3 mg/kg bw/day at the 97.5 th percentile. These values are lower than the previously reported exposure estimates at Tier 3. The corresponding reduction of refined exposure estimates at Tier 3 for European children, range from 0.1-0.4 mg/kg bw/day at the mean and from 0.1-1.0 mg/kg bw/day at the 95 th /97.5 th percentile. In 2010 the estimated exposure at Tier 2 for adults was 0.8 mg/kg bw/day (mean) and 3.2 mg/kg bw/day (95 th percentile) and, for children between 0.5 to 3.4 mg/kg bw/day (mean) and 1.2 to 7.2 mg/kg bw/day (95 th percentile). Combining the estimated intakes of lutein from the diet and from its use as food colour leads to an overall exposure of adults not exceeding the ADI of 1 mg/kg bw/day at the mean and 95 th percentile, which is in contrast to the previous exposure assessment. For children, the ADI would also not be exceeded at the mean, but would be exceeded at the 95 th /97.5 th percentile in The Netherlands and, UK. European Food Safety Authority, 2012 KEY WORDS Lutein, E 161b. 1 On request from EFSA, Question No EFSA-Q-2011-00807, adopted on 14 February 2012. 2 Panel members: F. Aguilar, R. Crebelli, B. Dusemund, P. Galtier, J. Gilbert, D.M. Gott, U. Gundert-Remy, J. König, C. Lambré, J-C. Leblanc, A. Mortensen, P. Mosesso, D. Parent-Massin, I.M.C.M. Rietjens, I. Stankovic, P. Tobback, D. H. Waalkens-Berendsen, R.A. Woutersen, M.C. Wright. Correspondence: ans@efsa.europa.eu Suggested citation: EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS); Scientific Opinion on the safety assessment of the exposure to lutein preparations based on new data on the use levels of lutein. EFSA Journal 2012;10(3):2589. [10 pp.] doi:10.2903/j.efsa.2012.2589. Available online: www.efsa.europa.eu/efsajournal European Food Safety Authority, 2012

SUMMARY Following a request by the European Food Safety Authority (EFSA) (self-task), the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) carried out a new exposure assessment of lutein (E 161b) from its use as a food colour based on corrected data provided by the food industry on the actual use levels. In its opinion of 7 July 2010, the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) established an Acceptable Daily Intake (ADI) for lutein (E 161b) of 1 mg/kg bw/day. This ADI is based on the No Observed Adverse Effect Level (NOAEL) of 200 mg/kg bw/day (the highest dose level tested) in a 90-day rat study, the absence of developmental toxicity at dose levels up to 1000 mg/kg bw/day (the highest dose level tested), the fact that lutein is not genotoxic, the fact that in 90-day studies no effects on reproductive organs were observed, and the fact that lutein is a normal constituent of the diet, and by applying an uncertainty factor of 200 given the absence of a multigeneration reproductive toxicity study and of chronic toxicity/carcinogenicity studies. In its previous opinion (EFSA, 2010), the Panel estimated the exposure to lutein at Tier 2 (from its use as a food colour) for adults at 0.8 mg/kg bw/day at the mean and 3.2 mg/kg bw/day at 95 th percentile. For children, the Tier 2 estimates ranged from 0.5 to 3.4 mg/kg bw/day at the mean and from 1.2 to 7.2 mg/kg bw/day at 95 th percentile. Refined exposure estimates based on data on actual use (Tier 3) initially provided by the food industry resulted in exceedance of the ADI of 1 mg/kg bw/day at the upper end of the range due to the use of lutein as a food colour. On 11 April 2011, the CIAA provided EFSA with corrected use levels of lutein preparations. During its twenty-third plenary meeting in April 2011, the ANS Panel discussed the new corrected data provided by the industry. The Panel has considered that the new corrected use levels of lutein are significantly lower than the ones provided previously and has anticipated that they would have an important impact on Tier 3 exposure estimates. The new exposure estimates on Tier 3 taking into account the updated use levels for lutein are resulting in an exposure to lutein of European adults of 0.1 mg/kg bw/day at the mean and of 0.3 mg/kg bw/day at the 97.5 th percentile, which are considerably lower compared to the previously reported exposure estimates at Tier 3. A corresponding reduction of refined exposure estimates at Tier 3 was calculated by the Panel for European children, ranging from 0.1-0.4 mg/kg bw/day at the mean and from 0.1-1.0 mg/kg bw/day at the 95 th /97.5 th percentile. Combining the estimated intakes of lutein from its natural occurrence in the diet with the exposure from its use as food colour would lead to an overall exposure of adults which does not exceed the ADI of 1 mg/kg bw/day at the mean (0.14 mg/kg bw/day) and at the 95 th /97.5 th percentile (0.39 mg/kg bw/day), which is in contrast to the previous exposure assessment. For children, this ADI would also not be exceeded at the mean (0.16-0.53 mg/kg bw/day), but would still be exceeded at the 95 th /97.5 th percentile (0.42-1.32 mg/kg bw/day) in some European countries (The Netherlands, UK). EFSA Journal 2012;10(3):2589 2

TABLE OF CONTENTS Abstract... 1 Summary... 2 Table of contents... 3 Background as provided by EFSA... 4 Terms of reference as provided by EFSA... 4 Evaluation... 5 1. Introduction... 5 2. New exposure estimates... 6 3. Discussion... 8 Conclusions... 8 Documentation provided to EFSA... 9 References... 9 Glossary/abbreviations... 10 EFSA Journal 2012;10(3):2589 3

BACKGROUND AS PROVIDED BY EFSA Statement on exposure to lutein preparations based on new use levels According to the framework Directive 89/107/EEC on food additives, the Scientific Committee for Food (SCF) should be consulted before the adoption of provisions likely to affect public health, such as the drawing up of lists of additives and the conditions for their use. Accordingly, all food additives, prior to their authorization, have been evaluated for their safety by the SCF or its successor the European Food Safety Authority (EFSA). Directive 89/1077EEC as well as Regulation (EC) No 1333/2008 of the European Parliament and of the Council of 16 December 2008 on food additives which will apply as from January 2010, require that food additives must be kept under continuous observation and must be re-evaluated whenever necessary in the light of changing conditions of use and new scientific information. In addition Regulation (EC) No 1333/2008 requires that all food additives which were permitted before 20 January 2009 shall be subject to a new risk assessment carried out by EFSA. Regulation (EC) No 257/2010 of 25 March 2010 sets up a programme for the re-evaluation of approved food additives in accordance with Regulation (EC) No 1333/2008. On 7 July 2010, the Scientific Panel of Food Additives and Nutrient Sources added to Food (ANS) adopted a scientific opinion on the re-evaluation of lutein (E161b) as a food additive. On 11 April 2011, the CIAA provided EFSA with corrected use levels of lutein preparations. During its twenty-third plenary meeting in April 2011, the ANS Panel discussed the new corrected data provided by the industry. The Panel has considered that the new corrected use levels of lutein are significantly lower than the ones provided previously and has anticipated that they would have an important impact on Tier 3 exposure estimates. Therefore, the Panel has proposed a self-task mandate for the re-evaluation of the exposure estimates and their comparison to the ADI. TERMS OF REFERENCE AS PROVIDED BY EFSA The European Food Safety Authority asks it s Scientific Panel on Food Additives and Nutrient Sources added to Food to re-evaluate the exposure to lutein preparations based on new data on the use levels of lutein and to compare the exposure estimates to the ADI. EFSA Journal 2012;10(3):2589 4

EVALUATION 1. INTRODUCTION Following a request by the European Food Safety Authority (EFSA) (self-task), the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) carried out a new exposure assessment of lutein (E 161b) from its use as a food colour based on corrected data provided by the food industry on the actual use levels. In its opinion of 7 July 2010, the ANS Panel established an Acceptable Daily Intake (ADI) for lutein (E 161b) of 1 mg/kg bw/day. This ADI was based on the No Observed Adverse Effect Level (NOAEL) of 200 mg/kg bw/day (the highest dose level tested) in a 90-day rat study, the absence of developmental toxicity at dose levels up to 1000 mg/kg bw/day (the highest dose level tested), the fact that lutein is not genotoxic, the fact that in 90-day studies no effects on reproductive organs were observed, and the fact that lutein is a normal constituent of the diet, and by applying an uncertainty factor of 200 given the absence of a multigeneration reproductive toxicity study and of chronic toxicity/carcinogenicity studies. Refined exposure estimates for children based on data on actual use (Tier 3) provided by the food industry ranged from 0.2-2.2 mg/kg bw/day. High level intakes ranged from 0.7-5.7 mg/kg bw/day. Therefore, at the reported use levels, the ADI of 1 mg/kg bw/day will be exceeded at the upper end of the range due to the use of lutein as a food colour. Including an estimated dietary intake of lutein between 0.8 and 2.5 mg/day, equivalent to 0.01-0.04 mg/kg bw/day for a 60 kg person, results in a worst case scenario for combined exposure to lutein from its use as a food colour and its mean intake from other dietary sources that does exceed the ADI of 1 mg/kg bw/day. On 11 April 2011, the CIAA (Confederation of the Food and Drink Industries of the EU, since June 2011 FoodDrinkEurope) provided EFSA with corrected use levels of lutein preparations. During its twenty-third plenary meeting in April 2011, the ANS Panel discussed the new corrected data provided by the industry. The Panel considered that the new corrected use levels of lutein are significantly lower than the ones provided previously and has anticipated that they would have an important impact on Tier 3 exposure estimates. Therefore, the Panel made new exposure estimate calculations. Table 1 lists the data used for the previous exposure estimates at Tier 3 for lutein and the new data made available to the Panel. Table 1: Data on use levels for lutein used in the previous exposure estimate (EFSA, 2010) at Tier 3 and new data made available to the Panel Range Maximum reported use New maximum reported use Beverages level* level* (mg pigment**/l) (EFSA, 2010) (mg pigment/l) (mg pigment/l) Non-alcoholic flavoured drinks 1-85 85 15 Foodstuffs Range (mg pigment/kg) Maximum reported use level* (mg pigment/kg) New maximum reported use level* (mg pigment/kg) Confectionery 3-300 300 45*** Decorations & coatings 2-500 500 60*** Fine bakery wares (egg, Viennoiserie, biscuits, cakes, wafers) 2-100 100 10*** EFSA Journal 2012;10(3):2589 5

Edible ices 5-100 100 20 Desserts including flavoured milk products 1-15 15 15*** Sauces, seasonings (e.g. curry powder, 10-500 500 20 tandoori), pickles, relished, chutney, piccalilli Snacks: dry, savoury potato, cereal or starchbased 15-60 60 60*** snack products: extruded or expanded savoury snack products Savoury snack products and savoury coated 15-60 60 60*** nuts Edible cheese rind and edible chasings 60-120 120 120*** Soups 50 50 10 Meat and fish analogues based on vegetable protein 1.4-4.2 5 2.9 *All dosages ready-to-eat. ** pigment refers to the colouring principle (i.e. lutein) and not to the food colour preparation that is specified as E 161b. *** No new level was reported by CIAA; instead CIAA has stated that the use levels reported by NATCOL should be used. 2. NEW EXPOSURE ESTIMATES In its previous evaluation, the Panel calculated exposure estimates at Tier 2 (i.e. using the maximum permitted levels MPLs as described in the legislation 4 ) and Tier 3 (using maximum reported use levels as listed in Table 1). The Panel recalculated these Tier 3 exposure estimates by taking into account the new data on actual use levels provided to the Panel by the food industry using the same approach. Refined exposure estimates have been performed for Tier 3 using the maximum reported use levels presented in Table 1, both combined with national consumption data for children and the adult population. The Panel noted that its estimates could be considered as being conservative as it is assumed that all processed foods and beverages contain lutein added at maximum reported use levels. For adults, the Panel calculated the exposure based on the UK consumption survey, as the UK population is considered to be one of the highest consumers of soft drinks in Europe, and also because detailed individual food consumption data (UK NDNS, 2000-2001) were available from the UNESDA report (Tennant et al., 2006) and the Natural Food Colours Association (NATCOL) report (Tennant, 2007). Exposure estimates for children (1-14 years old, weighting 16-54 kg) have been performed by the Panel with the use of detailed individual food consumption data from 11 European countries (Belgium, France, the Netherlands, Spain, Italy, Finland, Greece, Cyprus, Czech Republic, Sweden and Germany) provided by the EXPOCHI ( Individual food consumption data and exposure assessment studies for children ) consortium (Huybrechts et al., 2010). As the UK is not part of the EXPOCHI consortium, estimates for UK children (1.5-4.5 years old) were made by the Panel with the use of detailed individual food consumption data (UK NDNS, 1992-1993) available from the UNESDA report (Tennant et al., 2006) and the NATCOL report (Tennant, 2007). Data from the EXPOCHI countries and UK data were used by the Panel to calculate from summary statistics (average all population and 95 th /97.5 th percentile for consumers only) the average and high level exposure to lutein based on the food categorisation of EU food colours and using maximum 4 European Parliament and Council Directive 94/36/EC of 30 June 1994 on colours for use in foodstuffs. OJ L 273, 10.9.94, p.13 EFSA Journal 2012;10(3):2589 6

permitted levels and maximum reported use levels. High level exposure (95 th /97.5 th percentile of consumers only) was based on the assumption that an individual might be a high level consumer of one food category 5 and would be an average consumer of the others. This approach has been tested several times by the Panel in the re-evaluation of food colours and has shown reasonable correlation with high level total intakes when using the raw individual food consumption data. Therefore, this approach was preferred for the calculations in order to avoid excessively conservative estimates. When considering the maximum reported use levels from Table 1, estimates reported for the UK adult population give a dietary exposure to lutein of 0.1 mg/kg bw/day at the mean and 0.3 mg/kg bw/day for high level consumers (97.5 th percentile). The main contributor (>10%) to the total anticipated mean exposure to lutein was non-alcoholic beverages (62%) (confectionary: 9%, desserts (incl. flavoured milk products): 7%). When considering the maximum reported use levels from Table 1, the dietary exposure of European children, ranged from 0.1 to 0.4 mg/kg bw/day at the mean, and from 0.1 to 1.0 mg/kg bw/day at the 95 th /97.5 th percentile. The main contributors to the total anticipated mean exposure to lutein (>10% in all countries, these contributions differed per country), were non-alcoholic beverages (22-64%). Desserts (incl. flavoured milk products) accounted for 13-47% in 11 countries, fine bakery wares for 12 to 29% in 4 countries, snacks for 11 to 18% in 3 countries, confectionary for 13-14% in 2 countries and sauces and seasonings for 21% in one country. Table 2: Summary of the anticipated exposure to lutein using a tiered approach (EC, 2001) in children and the adult population Tier 2. Maximum Permitted Levels (EFSA, 2010) Mean exposure Exposure 95 th or 97.5 th * percentile Tier 3. Maximum reported use levels (EFSA, 2010) Mean exposure Adult UK population (>18 years old) 0.8 3.2 0.6 1.6 Exposure 95 th or 97.5 th * percentile Tier 3. Maximum reported use levels (new data on actual use levels) Mean exposure Exposure 95 th or 97.5 th * percentile 0.1 0.3 Pre-school UK children (1.5-4.5 years old, 15 kg body weight) mg/kg bw/day 3.0 7.2 2.2 5.7 0.4 1.0 Children EXPOCHI population (1-10 years old, 25-30 kg body weight) 0.5-3.4 1.2-7.2 0.2-2.2 0.7-5.7 0.1-0.4 0.1-1.0 * For the UK population, estimates are based on the UNESDA report which gives the 97.5 th percentile intake (Tennant et al., 2006). 5 High consumption values of fruit wines (still or sparkling), cider, (except cidre bouché) and perry, aromatized fruit wines, cider and perry from UK adult data is not taken into account for the calculation of high percentile exposure when this food category appeared to be the highest p97.5 exposure. In this case, the second highest contributor is taken in the calculation. EFSA Journal 2012;10(3):2589 7

3. DISCUSSION The new data provided to the Panel by the food industry on actual use levels were lower than the data previously reported. The new exposure estimated at Tier 3 taking into account the updated use levels for lutein in the food categories listed in Table 1 are resulting in an exposure to lutein of European adults of 0.1 mg/kg bw/day at the mean and of 0.4 mg/kg bw/day at the 97.5 th percentile. These values are also considerably lower compared to the previously reported exposure estimates at Tier 3 of 0.6 mg/kg bw/day at the mean and 1.6 mg/kg bw/day at the 97.5 th percentile. A corresponding reduction of refined exposure estimates at Tier 3 was calculated by the Panel for European children, ranging from 0.1-0.4 mg/kg bw/day at the mean and from 0.1-1.0 mg/kg bw/day at the 95 th /97.5 th percentile. The mean intake of lutein from the diet due to its natural occurrence was estimated at 2.5 mg/day for both children and adults, equivalent to 0.1 mg/kg bw/day for children and 0.04 mg/kg bw/day for adults. The intake of lutein from the diet at the 95 th percentile was estimated to be 7 mg/day for both children (equal to 0.28 mg/kg bw/day) and adults (equal to 0.12 mg/kg bw/day). Combining these intakes of lutein with the exposure from its use as food colour would lead to an overall exposure of adults which does not exceed the ADI of 1 mg/kg bw/day at the mean (0.14 mg/kg bw/day) and at the 95 th /97.5 th percentile (0.39 mg/kg bw/day), which is in contrast to the previous exposure assessment. For children, this ADI would also not be exceeded at the mean for most European countries (0.16-0.53 mg/kg bw/day), but would be reached or exceeded at the 95 th /97.5 th percentile (0.42-1.32 mg/kg bw/day) in some European countries (The Netherlands, UK). As a reminder, the Tier 2 (using MPLs) exposure estimates gave a total exposure for adults of 0.8 mg/kg bw/day at the mean and of 3.2 mg/kg bw/day for high consumers. The main contributors to the total anticipated exposure to lutein (>10%) were non-alcoholic beverages. For children, the Tier 2 exposure estimates ranged from 0.5 to 3.4 mg/kg bw/day at the mean, and from 1.2 to 7.2 mg/kg bw/day at the 95 th percentile. The main contributors to the total anticipated mean exposure to lutein (>10% in all countries, these contributions differed per country), were soft drinks (up to 56%), fine bakery wares (e.g. viennoiserie, biscuits, cakes, wafer) (up to 48%), and desserts, including flavoured milk products (up to 53%). Sauces, seasonings (e.g. curry powder, tandoori), pickles, relishes, chutney and piccalilli accounted for up to 44% of exposure in six countries. CONCLUSIONS In its previous opinion (EFSA, 2010), the Panel estimated the exposure to lutein at Tier 2 (from its use as a food colour) for adults at 0.8 mg/kg bw/day at the mean and 3.2 mg/kg bw/day at 95 th percentile. For children, the Tier 2 estimates ranged from 0.5 to 3.4 mg/kg bw/day at the mean and 1.2 to 7.2 at 95 th percentile. In view of the new data on the actual use levels of lutein submitted by the food industry indicating a substantially lower actual use of lutein for the food categories non-alcoholic flavoured drinks, edible ices, sauces and seasonings, soups, and meat and fish analogues based on vegetable protein, the Panel estimated the combined exposure to lutein at Tier 3 from its use as food colour and from its intake from the diet to be below the ADI of 1 mg/kg bw for adults at the mean and at the 95 th percentile. For children, the combined exposure to lutein at Tier 3 would be below or at this ADI at the mean, but would be exceeded at the 95 th /97.5 th percentile in some European countries (The Netherlands, UK). EFSA Journal 2012;10(3):2589 8

DOCUMENTATION PROVIDED TO EFSA 1. B. Kettlitz, April 2011. CIAA preliminary clarification on occurrence data on lutein levels provided in December 2009. REFERENCES EC (European Commission), 1998. Report on Methodologies for the Monitoring of Food Additive Intake Across the European Union. Final Report Submitted by the Task Coordinator, 16 January 1998. Reports of a Working Group on Scientific Cooperation on Questions Relating to Food, Task 4.2. SCOOP/INT/REPORT/2 (Brussels: European Commission Directorate General I11 Industry). EC (European Commission), 2001. Commission of the European Communities (COM). 542 final. Report from the commission on dietary food additive intake in the European Union. Brussels, 01.10.2001. Available from: http://eur-lex.europa.eu/lexuriserv/site/en/com/2001/com2001_0542en01.pdf EFSA (European Food Safety Authority), 2010. Opinion of the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) on request of the European Commission related to the reevaluation of lutein (E 161b) as a food additive EFSA Journal 2010; 8(7):1678 [57 pp.]. Huybrechts I, Sioena I, Boon PE, De Neve M, Amiano P, Arganini C, Bower E, Busk L, Christensen T, Hilbig A, Hirvonen T, Kafatos A, Koulouridaki S, Lafay H, Liukkonen K-H, Papoutsou S, Lourdes R-B, Ruprich J, Rehurkova I, Mathilde K, Serra-Majem L, Turrini A, Verger E, Westerlund A, Tornaritis M, vanklaveren JD and De Henauw S, 2010. Long-term dietary exposure to different food colours in young children living in different European countries. Scientific report submitted to EFSA. EFSA-Q-2010-00787. Available from: http://www.efsa.europa.eu/en/scdocs/doc/53e.pdf Tennant D, 2006. Screening of colour intakes from non-alcoholic beverages. Report prepared for the Union of European beverages associations UNESDA. December, 57 pp. Tennant D, 2007. Screening potential intakes of natural food colours. Report provided for the Natural Food Colours Association, NATCOL. July, 38 pp. EFSA Journal 2012;10(3):2589 9

GLOSSARY/ABBREVIATIONS ADI Acceptable Daily Intake ANS CIAA EC EFSA EU EXPOCHI NATCOL NOAEL SCF Scientific Panel on Food Additives and Nutrient Sources added to Food FoodDrinkEurope until June 2011 known as Confederation of the Food and Drink Industries of the EU European Commission European Food Safety Authority European Union Individual food consumption data and exposure assessment studies for children Natural Food Colours Association No-Observed-Adverse-Effect Level Scientific Committee on Food EFSA Journal 2012;10(3):2589