Attachment 6 Risk Assessment - Micronutrients1 Application A470– Formulated Beverages SUMMARY AND CONCLUSIONS ..................................................................................230 INTRODUCTION................................................................................................................236 HAZARD IDENTIFICATION AND CHARACTERISATION ..........................................................236 DIETARY INTAKE ASSESSMENT...........................................................................................238 VITAMINS AND MINERALS...........................................................................................239 VITAMIN A..........................................................................................................................239 Β-CAROTENE.......................................................................................................................245 THIAMIN .............................................................................................................................251 RIBOFLAVIN........................................................................................................................252 NIACIN................................................................................................................................254 FOLATE...............................................................................................................................260 VITAMIN B6 (PYRIDOXINE)..................................................................................................263 VITAMIN B12 .......................................................................................................................268 VITAMIN C..........................................................................................................................270 VITAMIN D..........................................................................................................................273 VITAMIN E..........................................................................................................................279 BIOTIN ................................................................................................................................285 PANTOTHENIC ACID ............................................................................................................288 CALCIUM ............................................................................................................................290 CHROMIUM .........................................................................................................................296 COPPER ...............................................................................................................................298 IODINE ................................................................................................................................305 IRON ...................................................................................................................................309 MAGNESIUM .......................................................................................................................314 MANGANESE.......................................................................................................................319 MOLYBDENUM....................................................................................................................322 PHOSPHORUS ......................................................................................................................327 SELENIUM ...........................................................................................................................331 ZINC....................................................................................................................................337 REFERENCES.....................................................................................................................343 1 For the purpose of this report, the term ‘micronutrients’ is used for vitamins and minerals. 229 Summary and Conclusions Risk Assessment – Micronutrients A risk assessment has been conducted in relation to the addition of certain vitamins and minerals to formulated beverages at a level of 25 % of the recommended dietary intake (RDI) per 600 ml serve. These include: vitamin A, β-carotene, thiamin, riboflavin, niacin, folate, vitamin B6, B12, D, E, biotin, pantothenic acid, calcium, chromium, copper, iodine, iron, magnesium, manganese, molybdenum, phosphorus, selenium and zinc. The applicant has requested vitamin C to be added at 100% of the RDI per 600 ml serve. The results of the risk assessment are provided below and are summarised in Table 1. Micronutrients without risk for the general population For the following micronutrients, it is concluded that addition to formulated beverages at a level of 25% of the RDI per 600 ml (100% of RDI per 600 ml for vitamin C) would raise no public health and safety concerns for any sector of the population: β-carotene, thiamin, riboflavin, niacin, folate, vitamin B6, B12, C, D, E, pantothenic acid, calcium, magnesium, phosphorus and selenium. Micronutrients with some risk for sensitive subpopulations For the following micronutrients, it is concluded that while the general population is without risk, there may be a risk for certain sectors of the population: Copper: Individuals with Wilson’s disease, Indian childhood cirrhosis or idiopathic copper toxicosis may respond adversely to copper in formulated beverages at a level of 0.75 mg per 600 ml. Iodine: Individuals with thyroid disorders or a long history of iodine deficiency may respond adversely to iodine in formulated beverages at a level of 37.5 µg per 600 ml. Iron: Individuals who are homozygous for hereditary haemochromatosis are susceptible to iron overload, even at normal dietary iron intakes, and are generally advised to avoid iron- supplements and highly iron fortified foods. As the majority of individuals with this condition are not diagnosed until sufficient iron has accumulated to produce adverse effects, the addition of iron to formulated beverages at a level of 3 mg per 600 ml serve may be a concern to these individuals. Micronutrients with some risk for specific age groups For the following micronutrients, there are potential risks for specific age groups if they were permitted to be added to formulated beverages: Vitamin A: The dietary modelling results suggest that young children consuming formulated beverages may have excess intakes of retinol for several years and therefore be at risk of hepatoxicity. For all other age groups and life-stages, there is no appreciable risk posed by excess intake of retinol. There are potential safety concerns for children up to the age of 3 years, and maybe up to 6 years, with the addition of retinol to formulated beverages at a level of 187.5 µg in a 600 ml serve. 230 Manganese: An upper level of intake (UL) could not be established because of limitations with the human data and considerable uncertainty with the animal toxicity studies. The available data suggests that the margin between the intake level producing adverse effects in humans and animals and the estimated intake from food is very small. Based on the severity of the potential adverse effect (neurotoxicity), additional oral exposure to manganese beyond the levels normally present in food and beverages could pose a public health and safety risk. Therefore, there are potential safety concerns with the addition of manganese to formulated beverages at a level of 1.25 mg in a 600 ml serve. Zinc: Dietary modelling indicated that children up to 8 years of age, who are consumers of a diet high in zinc, are predicted to exceed the UL for zinc. For adolescents up to the age of 18 years, who are consumers of a diet high in zinc, the intake is predicted to be 80% of the UL of zinc. Chronic zinc toxicity is associated with symptoms of copper deficiency. These adverse effects include anaemia, neutropaenia and impaired immune response. Furthermore, the potential contribution from other sources (e.g. dietary supplements) has not been taken into consideration in the dietary intake assessment. The intakes of zinc may therefore be underestimated for children and adolescents up to the age of 18 years and, for this group, formulated beverages at a level of 3 mg per 600 ml serve pose a public health and safety risk. Micronutrients with insufficient data to assess risk For the following micronutrients there was insufficient data to characterise the potential risk: Biotin and Chromium: Due to insufficient data on potential adverse effects and only limited food composition data it was not possible to establish an UL for biotin and chromium or to undertake a complete dietary intake assessment. In the absence of sufficient information, it is currently not possible to evaluate the safety of the addition of biotin and chromium to formulated beverages. Molybdenum: An UL has been established based on reproductive effects in rats. While some food composition data are available for molybdenum, it is insufficient to undertake a complete dietary intake assessment at this present time. In the absence of sufficient information, it is not currently possible to evaluate the safety of the addition of molybdenum to formulated beverages. Assessment of permitted forms For pantothenic acid, biotin, chromium, manganese, molybdenum and selenium, currently there are no forms permitted in Standard 1.1.1 – Preliminary