Federal Institute for Risk Assessment Published by A. Domke, R. Großklaus, B. Niemann, H. Przyrembel, K. Richter, E. Schmidt, A. Weißenborn, B. Wörner, R. Ziegenhagen Use of Minerals in Foods Toxicological and nutritional-physiological aspects Part II Imprint BfR Wissenschaft A. Domke, R. Großklaus, B. Niemann, H. Przyrembel, K. Richter, E. Schmidt, A. Weißenborn, B. Wörner, R. Ziegenhagen Use of Minerals in Foods – Toxicological and nutritional-physiological aspects Federal Institute for Risk Assessment Press and Public Relations Office Thielallee 88-92 D-14195 Berlin Berlin 2005 (BfR-Wissenschaft 01/2006) 308 pages, 3 figures, 42 tables € 15 Printed by: Contents and binding BfR-Hausdruckerei Dahlem ISSN 1614-3795 ISBN 3-938163-11-9 BfR-Wissenschaft 3 Contents 1 Preface 11 2 Glossary and Abbreviations 13 3 Introduction 15 3.1 Description of the problem 15 3.2 Principles for the risk assessment of vitamins and minerals including trace elements 16 3.3 Method to derive maximum levels for individual products 17 3.3.1 Structure of the report 17 3.3.2 Principles to derive maximum levels for vitamins and minerals in food supplements and fortified foods 18 3.3.2.1 Theoretical foundations 18 3.3.2.1.1 Derivation of tolerable vitamin and mineral levels for additional intake through food supplements and fortified foods 19 3.3.2.1.2 Derivation of the total tolerable intake of a vitamin or mineral via food supplements or the total intake level for via fortified foods 19 3.3.2.1.3 Derivation of maximum levels for individual food supplements (TLFS) 20 3.3.2.1.4 Derivation of maximum levels for individual fortified foods (TLFF) 20 3.3.2.2 Practical implementation 21 3.4 Tabular overview of the results 21 3.5 References 25 4 Risk Assessment of Sodium 27 4.1 Summary 27 4.2 Nutrient description 28 4.2.1 Characterisation and identification 28 4.2.2 Metabolism, functions, requirements 28 4.2.3 Exposure (dietary and other sources, nutritional status) 31 4.3 Risk characterisation 33 4.3.1 Hazard characterisation (LOAEL, NOAEL) 33 4.3.2 Risks which can be linked in the long-term to high sodium or salt intakes 34 4.3.2.1 Cardiovascular risk factors and mortality 34 4.3.2.2 Carcinoma risk 36 4.3.2.3 Nephrolithiasis risk 36 4.3.2.4 Osteoporosis risk 36 4.3.2.5 Risk of kidney damage 36 4.3.2.6 Burden on water status 36 4.3.3 Deficiency, possible risk groups 37 4.3.3.1 Deficiency 37 4.3.4 Possible risk groups for deficiency 37 4.3.5 Relative excess, possible risk groups 38 4.3.5.1 Relative excess and pathological sodium regulation 38 4.3.6 Possible risk groups in conjunction with increasing supplementation with sodium/salt 39 4.4 Tolerable upper intake level for sodium 39 4.4.1 Derivation of a maximum level for sodium in food supplements 41 4 BfR-Wissenschaft 4.4.1.1 Possible management options 41 4.4.2 Derivation of a maximum level for sodium in fortified foods 42 4.4.2.1 Possible management options 42 4.5 References 47 5 Risk Assessment of Chloride 53 5.1 Summary 53 5.2 Nutrient description 53 5.2.1 Characterisation and identification 53 5.2.2 Metabolism, function, requirements 54 5.2.3 Exposure (dietary and other sources, nutritional status) 55 5.3 Risk characterisation 56 5.3.1 Hazard characterisation (NOAEL, LOAEL) 56 5.3.2 Deficiency, possible risk groups 57 5.3.3 Excessive intake, possible risk groups 57 5.4 Tolerable upper intake level for chloride 58 5.4.1 Derivation of a maximum level for chloride in food supplements and fortified foods 58 5.5 Gaps in knowledge 59 5.6 References 59 6 Risk Assessment of Potassium 61 6.1 Summary 61 6.2 Nutrient description 61 6.2.1 Characterisation and identification 61 6.2.2 Metabolism, function, requirements 62 6.2.3 Exposure (dietary and other sources, nutritional status) 66 6.3 Risk characterisation 68 6.3.1 Hazard characterisation (NOAEL, LOAEL) 68 6.3.2 Deficiency, possible risk groups 71 6.3.2.1 Deficiency 71 6.3.3 Possible risk groups 72 6.3.4 Excessive intake, possible risk groups 72 6.3.4.1 Excessive intake 72 6.3.5 Possible risk groups 73 6.4 Tolerable upper intake level for potassium 74 6.4.1 Derivation of a maximum level (TLNEM) for potassium in food supplements 75 6.4.1.1 Possible management options 75 6.4.2 Derivation of a maximum level (TLFS) for potassium in fortified foods 76 6.5 Gaps in knowledge 78 6.6 References 78 7 Risk Assessment of Calcium 89 7.1 Summary 89 7.2 Nutrient description 89 7.2.1 Characterisation and identification 89 7.2.2 Metabolism, function, requirements 90 7.2.3 Exposure (dietary and other sources, nutritional status) 93 7.3 Risk characterisation 95 BfR-Wissenschaft 5 7.3.1 Hazard characterisation (NOAEL, LOAEL) 95 7.3.2 Deficiency, possible risk groups 99 7.3.3 Excessive intake, possible risk groups 100 7.4 Tolerable upper intake level for calcium 101 7.4.1 Derivation of a maximum level for calcium in food supplements 102 7.4.1.1 Possible management options 102 7.4.2 Derivation of a maximum level for calcium in fortified foods 103 7.4.2.1 Possible management options 103 7.5 Gaps in knowledge 104 7.6 References 105 8 Risk Assessment of Phosphorus 109 8.1 Summary 109 8.2 Nutrient description 109 8.2.1 Characterisation and identification 109 8.2.2 Metabolism, function, requirements 110 8.2.3 Exposure (dietary and other sources, nutritional status) 111 8.3 Risk characterisation 114 8.3.1 Hazard characterisation (NOAEL, LOAEL) 114 8.3.2 Deficiency, possible risk groups 114 8.3.2.1 Deficiency 114 8.3.3 Excessive intake, potential risk groups 115 8.4 Tolerable upper intake level for phosphorus 116 8.4.1 Derivation of a maximum level for phosphorus in food supplements 117 8.4.1.1 Possible management options 117 8.4.2 Derivation of a maximum level for phosphorus in fortified foods 117 8.4.2.1 Possible management options 117 8.5 References 118 9 Risk Assessment of Magnesium 121 9.1 Summary 121 9.2 Nutrient description 121 9.2.1 Characterisation and identification 121 9.2.2 Metabolism, function, requirements 122 9.2.3 Exposure (dietary and other sources, nutritional status) 124 9.3 Risk characterisation 127 9.3.1 Hazard characterisation (NOAEL, LOAEL) 127 9.3.2 Deficiency, possible risk groups 128 9.3.2.1 Deficiency 128 9.3.3 Possible risk groups for deficiency 130 9.3.4 Excessive intake, possible risk groups 130 9.4 Tolerable upper intake level for magnesium 131 9.4.1 Derivation of a maximum level for magnesium in food supplements 131 9.4.1.1 Possible management options 131 9.4.2 Derivation of a maximum level (TLFS) for magnesium in fortified foods 134 9.4.2.1 Possible management options 134 9.5 Gaps in knowledge 136 9.6 References 136 6 BfR-Wissenschaft 10 Risk Assessment of Iron 145 10.1 Summary 145 10.2 Nutrient description 145 10.2.1 Characterisation and identification 145 10.2.2 Metabolism, function, requirements 148 10.2.3 Exposure (dietary and other sources, nutritional status) 157 10.3 Risk characterisation 159 10.3.1 Hazard characterisation (LOAEL, NOAEL) 159 10.3.2 Iron overload and risks linked to high intakes and higher iron stores 160 10.3.2.1 Other adverse effects 166 10.3.3 Deficiency, possible risk groups 166 10.3.3.1 Deficiency 166 10.3.4 Possible risk groups for deficiency 167 10.3.5 Excessive intake, possible risk groups 169 10.3.5.1 Excessive intake 169 10.3.6 Possible risk groups in conjunction with growing iron supplementation 169 10.4 Tolerable upper intake level for iron 169 10.4.1 Derivation of a maximum level for iron in food supplements 171 10.4.1.1 Possible management options 172 10.4.2 Derivation of a maximum level for food in fortified foods 172 10.4.2.1 Possible management options 172 10.5 References 173 11 Risk Assessment of Iodine 189 11.1 Summary 189 11.2 Nutrient description 189 11.2.1 Characterisation and identification 189 11.2.2 Metabolism, function, requirements 190 11.2.3 Exposure (dietary and other sources, nutritional status) 194 11.3 Risk characterisation 198 11.3.1 Hazard characterisation (NOAEL, LOAEL) 198 11.3.2 Deficiency, possible risk groups 199 11.3.2.1 Deficiency 199 11.3.3 Possible risk groups for insufficient intake 201 11.3.4 Excessive intake, possible risk groups 201 11.3.4.1 Excessive intake 201 11.3.5 Possible risk groups 206 11.4 Tolerable upper intake level for iodine 207 11.4.1 Derivation of a maximum level for iodine in food supplements 210 11.4.1.1 Possible management options 210 11.4.2 Derivation of a maximum level for iodine in fortified foods 210 11.4.2.1 Possible management options 211 11.5 Gaps in knowledge 212 11.6 References 212 12 Risk Assessment of Fluoride 227 12.1 Summary 227 12.2 Nutrient description 227 12.2.1 Characterisation and identification 227 BfR-Wissenschaft 7 12.2.2 Metabolism, functions, requirements 228 12.2.3 Exposure (dietary and other sources, nutritional status) 230 12.3 Risk characterisation 232 12.3.1 Hazard characterisation (NOAEL, LOAEL) 232 12.3.2 Deficiency, possible risk groups 233 12.3.3 Excessive intake, possible risk groups 233 12.4 Tolerable upper intake level for fluoride 234 12.4.1 Derivation of a maximum level for fluoride in food supplements 235 12.4.2 Derivation of a maximum level for fluoride in fortified foods 235 12.5 References 236 13 Risk Assessment of Zinc 239 13.1 Summary 239 13.2 Nutrient description 239 13.2.1 Characterisation and identification 239 13.2.2 Metabolism, functions, requirements 240 13.2.3 Exposure (dietary and other sources, nutritional status) 240 13.3 Risk characterisation 241 13.3.1 Hazard characterisation (NOAEL, LOAEL) 241 13.3.2 Deficiency, possible risk groups 242 13.3.3 Excessive intake, possible risk groups 242 13.4 Tolerable upper intake