The EFSA Journal (2008) 814, 1-9 SCIENTIFIC OPINION Calcium sulphate for use as a source of calcium in food supplements 1 Scientific Panel on Food Additives and Nutrient Sources added to food (Question No EFSA-Q-2005-075) PANEL MEMBERS Adopted on 24 September 2008 F. Aguilar, U. Charrondiere, B. Dusemund, P. Galtier, J. Gilbert, D.M. Gott, S. Grilli, R. Guertler, G.E.N. Kass, J. Koenig, C. Lambré, J-C. Larsen, J-C. Leblanc, A. Mortensen, D. Parent-Massin, I. Pratt, I. Rietjens, I. Stankovic, P. Tobback, T. Verguieva, R. Woutersen. SUMMARY Following a request from the Commission, the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) has been asked to evaluate the safety and bioavailability of calcium sulphate for use as a source of calcium in food supplements. The present opinion deals only with the safety and bioavailability of a particular source of calcium, calcium sulphate, to be used as a nutritional substance in food supplements. The safety of calcium itself, in terms of the amounts that may be consumed, is outside the remit of this Panel. The Panel noted that the safety of calcium sulphate when used as a food additive has been evaluated by the Scientific Committee on Food (SCF) and the FAO/WHO Joint Expert Committee on Food Additives (JECFA) who allocated an Acceptable Daily Intake (ADI) not specified for the respective calcium and sulphate ions. The SCF also allocated a tolerable upper intake level of 2500 mg calcium/day. Calcium sulphate as a source of calcium in food for particular nutritional uses and in foods intended for the general population was evaluated by the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC). This present opinion is predominately based on these previous opinions. Calcium sulphate (gypsum, CaSO 4 ) exists in an anhydrous form and as a dihydrate. It is only slightly soluble in water. It is permitted as a food additive in most foods with no other restriction other than good manufacturing practice. It is intended to be used in food supplements as an alternative source of calcium and the petitioner estimates that the daily dose is unlikely to exceed 800 mg calcium (equivalent to 2.7 g calcium sulphate/day), which is the Recommended Daily Allowance defined in Directive 90/496/EEC on nutritional labelling. 1 For citation purposes: Scientific Opinion of the Panel on Food Additives and Nutrient Sources added to Food on a request from the Commission on Calcium sulphate for use as a source of calcium in food supplements. The EFSA Journal (2008) 814, 1-9. European Food Safety Authority, 2008
A single feeding study in rats indicated no difference in calcium bioavailability from a diet with added calcium sulphate or calcium from other sources. Human studies indicate that the bioavailability of calcium from calcium sulphate in mineral waters is comparable to that from milk and that the sulphate anion does not affect the urinary excretion of calcium. Although human studies were not available for food, the AFC Panel concluded in 2004 that the bioavailability of calcium from calcium sulphate in other foods is not expected to differ from that of already permitted calcium sources in foods for particular nutritional uses. If calcium sulphate as a worst case scenario would be assumed to be consumed up to the tolerable upper intake level of 2500 mg calcium per day this would correspond to an intake of 8.5 g calcium sulphate (anhydrous) per day. This would amount to a daily intake of 6 g sulphate ion. JECFA states that the few available studies in experimental animals do not raise concern about the toxicity of the sulphate ion in sodium sulphate. Sodium sulphate is used clinically as a laxative. In clinical trials using 2-4 oral doses of up to 4.5 g sodium sulphate decahydrate per person (9 18 g per person) only occasional loose stools were reported. These doses correspond to 2.7 5.4 g sulphate ion. Because of the low solubility of calcium sulphate compared with sodium sulphate it can be expected that the sulphate ion would not be present as a bolus dose after ingestion of calcium sulphate, but would rather dissociate at a lower rate. On the basis of available studies the ANS Panel considers that the bioavailability of calcium from calcium sulphate is comparable to other inorganic calcium salts and that the use of calcium sulphate as a source of calcium in food supplements is of no safety concern assuming the total dietary exposure to calcium remains within the defined tolerable upper intake level and that the commercially available calcium sulphate will comply to the existing specifications as laid down in Directive 2000/63/EC. Key words: Calcium sulphate, CAS Number 7778-18-9 (anhydride), CAS Number 10101-41-4 (dihydrate), food supplement. The EFSA Journal (2008) 814, 2-9
TABLE OF CONTENTS Panel Members...1 Summary...1 Table of Contents...3 Background as provided by the Commission...4 Terms of reference as provided by the Commission...4 acknowledgements...4 Assessment...5 1. Introduction...5 2. Technical data...5 2.1. Chemistry...5 2.2. Specifications...5 2.3. Case of need and proposed uses...5 2.4. Exposure...6 2.5. Existing authorisations and evaluations...6 3. Biological and toxicological data...6 3.1. Bioavailability of calcium from the source...6 3.2. Toxicological data on calcium sulphate...6 4. Discussion...7 Conclusion...7 Documentation provided to EFSA...7 References...7 Glossary / Abbreviations...9 The EFSA Journal (2008) 814, 3-9
BACKGROUND AS PROVIDED BY THE COMMISSION The European Community legislation lists nutritional substances that may be used for nutritional purposes in certain categories of foods as sources of certain nutrients. The Commission has received a request for the evaluation of calcium sulphate added for nutritional purposes to food supplements. The relevant Community legislative measure is: - Directive 2002/46/EC of the European Parliament and of the Council on the approximation of the laws of the Member States relating to food supplements. 2 TERMS OF REFERENCE AS PROVIDED BY THE COMMISSION In accordance with article 29 (1) (a) of the Regulation (EC) No. 178/2002, the European Commission asks the European Food Safety Authority (EFSA) to provide a scientific opinion, based on its considerations of the safety and bioavailability of calcium sulphate added for nutritional purposes to food supplements. ACKNOWLEDGEMENTS The European Food Safety Authority wishes to thank the members of the Working Group B on Food Additives and Nutrient Sources of the ANS Panel for the preparation of this opinion: D. Boskou, R. Charrondiere, B. Dusemund, D. Gott, T. Hallas-Møller, K.F.A.M. Hulshof, J. König, D. Parent-Massin, I. Rietjens, G.J.A. Speijers, P. Tobback, T. Verguieva, R. Woutersen. 2 OJ L183, 12.7.2002, p51 The EFSA Journal (2008) 814, 4-9
ASSESSMENT The present opinion deals only with the safety and bioavailability of a particular source of calcium, calcium sulphate, to be used as a nutritional substance in food supplements. The safety of calcium itself, in terms of the amounts that may be consumed, is outside the remit of this Panel. 1. Introduction The ANS Panel noted that the safety of calcium sulphate as a food additive has been evaluated by the Scientific Committee on Food (SCF) when an ADI not specified was allocated for the respective calcium and sulphate ions (SCF, 1990). Calcium sulphate as a source of calcium in food for particular nutritional uses and in foods intended for the general population has been evaluated by the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) (EFSA, 2003; EFSA, 2004). This present opinion is predominantly based on these previous opinions. 2. Technical data 2.1. Chemistry Calcium sulphate, CaSO 4 2H 2 O, gypsum, E 516 The CAS number for calcium sulphate: Anhydrous 7778-18-9 Dihydrate 10101-41-4 EINECS number: 231-900-3 Molecular weight (anhydrous form): 136.14 g/mol Calcium sulphate is a fine, white to slightly yellowish-white odourless powder. It is slightly soluble in water (2g/l at 20 C). 2.2. Specifications The petitioner indicates that the product in question complies with the present specification for calcium sulphate as a food additive (EC, 2000). The percentage of sulphate in calcium sulphate anhydrous is 71% on a weight basis. 2.3. Case of need and proposed uses Calcium sulphate is to be used as a source of calcium in food supplements. According to the petitioner the quantity of calcium (as calcium sulphate) to be added to food supplements will be determined by individual formulators but is normally the quantity necessary to supply up to 800 mg/day of calcium. European Food Safety Authority, 2008
2.4. Exposure Calcium sulphate as a source of calcium in food supplements According to the petitioner the anticipated exposure of the population to calcium in food supplements is by self-selection of products containing Multivitamins & Multiminerals or of more specific combinations providing calcium. The petitioner states that typical levels of calcium included in Multivitamin and Mineral Tablets is often only 10-30% of the RDA of 800 mg (80 240 mg calcium). Food supplement products containing calcium at levels of up to 800 mg/day have been on free sale in EU Member States for at least 20 years. This level is often achieved in calcium or calcium and vitamin D products by inclusion of 400 mg calcium/chewable tablet with a dose of 2 tablets/day. 2.5. Existing authorisations and evaluations Calcium sulphate is authorised as food additive permitted quantum satis (q.s.) to all foods, which may contain food additives according to the Directive on food additives other than colours and sweeteners (EC, 1995). Calcium sulphate was evaluated by the Scientific Committee on Food (SCF), which allocated an ADI not specified for the respective ions calcium and sulphate (SCF, 1990) when used as food additive (E 516). The FAO/WHO Joint Expert Committee on Food Additives (JECFA) similarly allocated ADI not specified for the calcium and sulphate ions (JECFA, 1986). SCF also allocated a tolerable upper intake level of 2500 mg calcium/day as a nutrient (SCF 2003) According to the petitioner calcium sulphate is an approved additive on the Food and Drug Administration GRAS (Generally Recognized As Safe) list of food additives. Approvals for the use of calcium sulphate in specific food products for nutritional and functional uses are listed in FDA Regulations, Title 21, Food and Drugs, Parts 1 to 199, Revised April 1, 1985. 3. Biological and toxicological data 3.1. Bioavailability of calcium from the source A single feeding study in rats indicated no difference in calcium bioavailability from a diet with added calcium sulphate or other calcium sources (carbonate, chloride, hydroxide, sulphate, oxide, lactate, acetate, propionate or yeast) (EFSA, 2004). The human studies indicated that the bioavailability of calcium from calcium sulphate in mineral water is comparable to that from milk and that the sulphate anion does not affect the urinary excretion of calcium. The AFC Panel concluded that the bioavailability of calcium from calcium sulphate in other foods is not expected to differ from that of other already permitted calcium sources in foods for particular nutritional uses (EFSA, 2004). 3.2. Toxicological data on calcium sulphate No data on toxicological aspects were submitted by the petitioner. The EFSA Journal (2008) 814, 6-9
4. Discussion Calcium sulphate as a source of calcium in food supplements If calcium sulphate as a worst case scenario would be assumed to be consumed up to the tolerable upper intake level of 2500 mg calcium per day this would correspond to an intake of 8.5 g calcium sulphate (anhydrous) per day. This would amount to a daily intake of 6 g sulphate ion per person. For sodium sulphate JECFA states that the few available studies in experimental animals do not raise concern about the toxicity of the sulphate ion. Sodium sulphate is used clinically as a laxative. In clinical trials using 2-4 oral doses of up to 4.5 g sodium sulphate decahydrate per person (9 18 g per person) only occasional loose stools were reported. These doses correspond to 2.7 5.4 g sulphate ion (EFSA, 2004). Because of the low solubility of calcium sulphate compared with sodium sulphate it can be expected that the sulphate ion would not be present as a bolus dose after ingestion of calcium sulphate, but would rather dissociate at a lower rate. Therefore the ANS Panel concludes that the studies with dose levels up to 5.4 g sulphate ion from sodium sulphate per person provide sufficient reassurance over the safety of a worst case exposure scenario to the 6 g of sulphate ion from calcium sulphate. Given the previous evaluations of the calcium and sulphate ions and calcium sulphate as a food additive (JECFA, 1986; SCF, 1990), the ANS Panel considered that a new toxicological evaluation of calcium sulphate was not needed for this present opinion. CONCLUSION On the basis of the available information, the ANS Panel concludes that the bioavailability of calcium from calcium sulphate is comparable to other inorganic calcium salts and that the use of calcium sulphate as a source of calcium in food supplements is of no safety concern assuming that the total dietary exposure to calcium remains within the defined tolerable upper intake level and that the calcium sulphate will comply with the existing specifications as laid down in Directive 2000/63/EC. DOCUMENTATION PROVIDED TO EFSA 1. Dossier on calcium sulphate. February 2005. Submitted by Health Food Manufacturers Association, UK. REFERENCES EC, 1995. Commission Directive 95/2/EC of 20 February 1995 on food additives other than colours and sweeteners. OJ L 61, 18.3.1995, p. 1. EC, 2000. Commission Directive 2000/63/EC of 5 October 2000 amending for the second time Commission Directive 96/77/EC of 2 December 1996 laying down specific purity criteria on food additives other than colours and sweeteners. OJ L277, 30.10.2000 p. 1. EFSA, 2003. Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) on a request from the Commission related to calcium sulphate for use in foods for particular nutritional uses (Question number EFSA-Q- 2003-124). The EFSA Journal 20, 1-6. http://www.efsa.europa.eu/efsa/scientific_opinion/opinion_afc_03_en1.pdf The EFSA Journal (2008) 814, 7-9
EFSA, 2004. Opinion of the Scientific Panel on Food additives, Flavourings, Processing Aids and Materials in Contact with food (AFC) related to Calcium Sulphate as a mineral substance in foods intended for the general population (Question number EFSA-Q-2003-237). The EFSA Journal 112, 1-10. http://www.efsa.europa.eu/efsa/scientific_opinion/afc_opinion23_ej112_calsulminsub_en 1,3.pdf JECFA, 1986. Evaluation of certain food additives and contaminants. Twenty-ninth report of the Joint FAO/WHO Expert Committee on Food Additives. WHO Technical Report Series, No. 733, 1986, and corrigendum. SCF, 1990. First series of food additives of various technological functions. Reports of the Scientific Committee for Food (25 th series). Opinion expressed on May 18, 1990. Directorate-General Internal Market and Industrial Affairs, 1991. http://ec.europa.eu/food/fs/sc/scf/reports/scf_reports_25.pdf SCF, 2003. Opinion of the Scientific Committee on Food on the tolerable upper level of calcium. Opinion expressed on 4 April 2003. http://ec.europa.eu/food/fs/sc/scf/out194_en.pdf The EFSA Journal (2008) 814, 8-9
GLOSSARY / ABBREVIATIONS ADI ADI not specified AFC EC EFSA JECFA GRAS RDA SCF Acceptable Daily Intake It is a term used when, on the basis of the available toxicological, biochemical and clinical data, the total daily intake of the substance, arising from its natural occurrence and/or its present use in food at the levels necessary to achieve the desired technological effect, will not represent a hazard to health Scientific Panel on food additives, flavourings, processing aids and materials in contact with food European Commission European Food Safety Authority FAO/WHO Joint Expert Committee on Food Additives Generally Recognized As Safe Recommended Daily Allowance Scientific Committee for Food The EFSA Journal (2008) 814, 9-9