Risk Assessment of Magnesium in Food Supplements

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk associated with magnesium in food supplements. VKM is requested to evaluate upper tolerable intake levels for magnesium and high and low intakes in the Norwegian population. Pending establishment of common maximum limits in the EU, the NFSA is evaluating the national maximum limits for vitamins and minerals in food supplements. This risk assessment is the scientific basis for NFSA's evaluation of national limits for magnesium. Directive 2002/46/EC on food supplements was implemented in Norwegian law in 2004 in Regulation 20 May 2004 No. 755 on food supplements. Common maximum and minimum levels of vitamins and minerals in food supplements shall be set in the EU. Until common limits are established in the EU, the national limits apply. The present report is a risk assessment of magnesium in food supplements. It is based on published articles retrieved from literature searches and previous risk assessments of magnesium. Magnesium is an essential alkaline mineral and occurs as free cation Mg2+ in aqueous solution, or as the mineral part of a large variety of compounds such as chlorides, carbonates and hydroxides. Dietary sources of magnesium include green leafy vegetables, legumes, whole grain cereals, dark chocolate, nuts, fish and seafood, banana and coffee. NFSA has especially requested VKM to consider water as a source of magnesium. A few waterworks reported magnesium concentrations at 10 mg/L. Consumption of water from these waterworks may contribute up to 10% of recommended magnesium intake. However, most waterworks reported negligible magnesium concentrations. Magnesium has multiple functions in the body; it is a required cofactor for more than 300 enzyme systems in the body; for energy-dependent membrane transport, for gene regulation, and for sustained electrical potential in excitable cells. Magnesium also plays a major role in bone and mineral homeostasis. No tolerable upper intake level (UL) has been established for magnesium intake from food sources for the reason that no adverse effects have been recognised in healthy populations. Magnesium salts in food supplements may cause osmotic diarrhoea which is the most frequently reported adverse effect. However, these effects are considered relatively mild. Previous reports have arrived on UL or guidance levels (GLs) for supplemental magnesium ranging from 250 mg/day in the EU (Scientific Committee for Food (SCF, 2001)) through 350 mg/day in the USA (Institute of Medicine (IOM, 1997)) and up to 400 mg per day in the UK (Expert group on Vitamins and Minerals (EVM, 2003)). The UL from SCF (2001) is below the recommended daily dietary intakes for adults. Since the critical endpoint (gastrointestinal symptoms) is mild, rapidly reversible and no NOAEL could be identified, VKM finds it appropriate to base the UL for magnesium salts in food supplements on the LOAEL from IOM (1997). For the same reason, an uncertainty factor of 1 may be applicable for establishing a UL for magnesium salts in food supplements. VKM therefore proposes an amendment of the ULs suggested by SCF (2001) for magnesium in supplements. The IOM (1997) suggestion of a UL at 350 mg supplementary magnesium per day for adults was based on a LOAEL for mild diarrhea. VKM found no results to support an alteration of this UL. VKM therefore suggests a UL of 350 mg magnesium in food supplements per day in adults which is in accordance with the UL suggested by (IOM, 1997). This UL will also cover the recommended intakes for the adult population. VKM suggests that the ULs for children equal the recommended intakes for each age group: Age group ULs (mg/day) Children 1-3 years 85 Children 3-10 years 120-200 Children (10-<14 years) 280 Adolescents (14-<18 years) 280 Adults (≥18 years) 350 According to the habitual dietary intakes of magnesium estimated from nationwide dietary surveys in Norway, about 25% of adults have intakes of magnesium below the recommendations from food and supplements. Almost the same percentage was below the recommended intakes among 9-year-old children, while approximately 70% of 13-year-olds had an intake of magnesium below the recommendations. It should be noted that the intakes have been estimated with use of different dietary survey methods for the different age categories and a comparison of estimates across age groups can be misleading and has a high degree of uncertainty. Concentration of magnesium in water is low and about 60% of the waterworks reporting to the Norwegian Waterworks Registry had a magnesium concentration below 2 mg/L, indicating water as a negligible source of magnesium for the majority of the population.

Assessment of Iron Intake in Relation to Tolerable Upper Intake Levels

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the intake of iron in the Norwegian population in relation to tolerable upper intake levels (ULs). The existing maximum limit for iron in food supplements is 27 mg/day. VKM has also conducted scenario calculations to illustrate the consequences of amending the maximum limit to 5, 10, 20, 30, 40 or 50 mg/day. Iron deficiency is one of the most common nutritional disorders in the world. Individuals with increased iron demand such as growing children and pregnant women, those who experience blood loss such as menstruating women are particularly at risk for the consequences or iron deficiency. Iron deficiency can lead to fatigue and anaemia. The most common adverse effects of iron supplementation are reversible gastrointestinal symptoms. Chronic iron excess can lead to iron overload which is associated with several irreversible severe health outcomes such as cancers and cardiovascular diseases. Up to 1% of the population have a genetic trait that leads to accumulation of iron and renders them more vulnerable to iron excess. An adult needs approximately 10 mg iron per day to overcome daily loss. The tolerable upper intake level (UL) for iron in adults range from 45 to 60 mg/day. However, all previous reports acknowledge the challenges in defining upper levels. The Expert Group on Vitamins and minerals (EVM), UK report provided a guidance level (GL) of 17 instead of a UL and the Nordic Nutrition Recommendations (NNR) (2012) suggested an UL of 60 mg/day, but did not suggest any clear upper levels for children. Institute of Medicine (IOM), US (2001) gives the most substantiated tolerable upper intake levels based on gastrointestinal effects, which is 40 mg/day for infants and children, regardless of age, and 45 mg/day for adolescents and adults. The Joint FAO/WHO Expert Committee on Food Additives 2003 (JECFA) also took the potential serious effects of iron overload into account and suggested a GL of 50 mg/day in adults or 0.8 mg/kg per day in children and adolescents. Because the risks and consequences from overload are significant and potentially serious, VKM suggests that the GL from JECFA (2003) is used. Using the GL from JECFA (2003), none of the suggested doses can be given to 2 or 4-yearold children, 9 year olds can add 5 mg iron from supplements, 13 year olds 20, and adults 30 mg without exceeding the guidance levels.

Assessment of Vitamin B6 Intake in Relation to Tolerable Upper Intake Levels

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the intake of vitamin B6 (pyridoxine) in the Norwegian population in relation to tolerable upper intake levels (ULs). The existing maximum limit for vitamin B6 in food supplements is 4.2 mg/day. VKM has also conducted scenario calculations to illustrate the consequences of amending the maximum limitto 2, 6, 8, 10, 20 or 25 mg/day. Vitamin B6 is water soluble and comprises six compounds with vitamin B6 activity; pyridoxine (PN, an alcohol), pyridoxal (PL, an aldehyde) and pyridoxamine (PM, the amine) and their corresponding phosphates; pyridoxine 5’-phosphate (PNP), pyridoxal 5’ -phosphate (PLP) and pyridoaxamin 5’ –phosphate (PMP). These six forms of vitamin B6 are all present in food in addition to the glycosylated form, pyridoxine-5’-β-δ-glucoside (PNG), in some plants. In food supplements the most common vitamin B6 form is pyridoxine hydrochloride. Eighty to ninety percent of vitamin B6 in the body is found in muscles and estimated body stores in adults amount to about 170 mg with a half-life of 25-33 days. Vitamin B6 deficiency is mostly seen in combination with deficiency of other B vitamins. Symptoms of vitamin B6 deficiency are anaemia and neurological abnormalities (EFSA, 2016). Intakes of vitamin B6 from the diet alone have not been reported to cause adverse effects. Sensory neuropathy has been reported to be the most sensitive adverse health effect of vitamin B6 supplementation. VKM proposes to adopt the tolerable upper intake level (UL) set by the Scientific Committee for Food (SCF) in 2000 at 25 mg/day for vitamin B6, which was based on a lowest observed adverse effect level (LOAEL) of 100 mg/day found in one randomised controlled trial. VKM recognises that there are no well-designed dose-response studies of long-term use available. However, for adults, no adverse effects have been reported at doses with vitamin B6 up to 25 mg/day. Dietary calculations have been performed for mean intakes and in various percentiles (P5, P25, P50, P75 and P95) in children (2-, 4- and 9-year-olds), adolescents (13-year-olds) and in adults. To illustrate the consequences of amending the maximum limit for vitamin B6 in food supplements to 2, 6, 8, 10, 20 or 25 mg/day in the different age groups, VKM has used the scenarios with P95 from food and added the alternative amounts of supplements. VKM has compared these scenarios with the tolerable upper intake levels set by the Scientific Committee for Food in 2000 for adults, adolescents and children. In these scenarios, the 2- and 4-year-old children will exceed the tolerable upper intake level with use of 6 mg/day or higher vitamin B6 in supplements. The 9-year-old children will exceed the tolerable upper intake level with supplemental use of 10 mg/day. The 13-year-old adolescents will exceed the tolerable upper intake level with 20 mg/day of vitamin B6 in supplements. Adults will exceed the tolerable upper intake level with use of 25 mg/day of vitamin B6/pyridoxine in supplements.

Assessment of Vitamin E Intake in Relation to Tolerable Upper Intake Levels

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the intake of vitamin E (alpha-tocopherol) in the Norwegian population in relation to tolerable upper intake levels (ULs). The existing maximum limit for vitamin E in food supplements is 30 mg/day. VKM was also requested to conduct scenario calculations to illustrate the consequences of amending the maximum limit for alpha-tocopherol to 15, 50, 100, 150, 200 and 300 mg/day. Naturally vitamin E is a fat soluble compound synthesised by plants and consists of eight different tocopherols (α-, β-, γ- and δ- tocopherols and α-, β-, γ- and δ- tocotrienols) with varying vitamin E antioxidant activity. α-Tocopherol is recognised to meet human vitamin E requirements and accounts for 90% of the activity in human tissue. Vitamin E activity in food is expressed as α-tocopherol equivalents (α-TE) and 1 α-TE is defined as 1 mg d-αtocopherol. The physiological role of vitamin E is to react with free radicals in cell membranes and other lipid milieu, thereby preventing polyunsaturated fatty acids (PUFA) from being damaged by lipid peroxidation. This antioxidant activity is important to maintain membrane integrity and takes place in all cells in the body. Vitamin E deficiency symptoms include peripheral neuropathy, ataxia, myopathy and retinopathy. Vitamin E is dependent on lipid and lipoprotein metabolism and it takes decades for body depletion. The Norwegian recommended intakes for vitamin E for adults are 10 αTE/day for men and 8 α-TE/day for women. There is no evidence of adverse effects from the consumption of vitamin E naturally occurring in foods. Animal studies have shown that α-tocopherol is not mutagenic, carcinogenic or teratogenic. However, high doses of α-tocopherol supplements can cause haemorrhage and interrupt blood coagulation. VKM propose to adopt the tolerable upper intake level set by the Scientific Committee for Food Safety (SCF) which is based on one human dose-response study. Hence, the upper level for supplemental vitamin E is suggested to 300 mg/day for adults. The upper level for children and adolescents is derived from scaling the adult upper level based on body surface area (body weight 0.75). The tolerable upper intake levels set for vitamin E concern only intake from supplements, since intake of vitamin E from the diet is considered safe. VKM has therefore not conducted or evaluated scenarios with intake from both diet and supplements. Dietary calculations have, however, been performed for intake in various percentiles (P) P5, P25, mean, P50, P75 and P95 in children (2- 4- and 9-year-olds), adolescents (13-year-olds) and in adult men and women as background information. Mean and median intakes of vitamin E are above the recommended intakes for all age groups. No age group reaches the recommended intake at P5, and 9- and 13-year-old boys and 9-year-old girls do not reach the recommended intake at P25 from diet alone. Because the tolerable upper intake level for supplemental vitamin E for adults is 300 mg/day, none of the suggested amendments of the maximum limit in food supplements (to 15, 50, 100, 150, 200 and 300 mg/day) will lead to exceedance of this upper level in adults. In 13year-olds supplements with 300 mg/day vitamin E will lead to exceedance of the upper level. In 9-year-olds supplements with 200 mg/day vitamin E will lead to exceedance of the upper level. In 4- and 2-year-olds supplements with 150 mg/day vitamin E will lead to exceedance of the upper level. Vitamin E intake from fortified products is not included in the calculations, but are however, evaluated to be very low.

Assessment of Zinc Intake in Relation to Tolerable Upper Intake Levels

The Norwegian Food Safety Authority (NFSA, Mattilsynet) has requested the Norwegian Scientific Committee for Food Safety (VKM) to assess the intake of iron zinc in the Norwegian population in relation to tolerable upper intake levels (ULs). The existing maximum limit for zinc in food supplements is 25 mg/day. VKM has also conducted scenario calculations to illustrate the consequences of amending the maximum limit to 1, 2, 5, 10, 15 or 20 mg/day. Zinc is an essential trace element required for RNA, DNA and protein synthesis, cellular division, differentiation and growth (Mac Donald, 2000). Zinc is required for catalytic function in several enzymes and participates in all major biochemical pathways in the body. The function of the immune system depends on the ability of its cells to proliferate and differentiate, which is impaired in individuals with suboptimal zinc status (Barton et al. 2000). Due to its role in cell division and differentiation, adequate zinc nutrition is particularly important in children, and the requirements per kg body weight are highest in early life. The endogenous intestinal losses can vary from 7 mmol/day (0.5 mg/day) to more than 45 mmol/day (3 mg/day), depending on zinc intake (King and Turnlund, 1989). The requirements for zinc vary according to age and bioavailability. Several bioactive compounds in food such as tannins and phytic acids interact with zinc absorption and increase zinc requirements. The requirements vary twenty-fold according to life stage and diet. Zinc supplements, even at or slightly above the recommended intakes, can cause nausea and vomiting. The main concern with chronic zinc excess is, however, copper deficiency which is associated with several chronical illnesses. However, copper deficiency is uncommon due to the ubiquitous presence of copper in the diet. VKM proposes to use the ULs set by IOM (2001) as they provide values also for children and adolescents. The tolerable upper intake level set for adults is 40 mg zinc per day from food (and water) and supplements. Based on the scenario estimations, a dietary zinc intake at the 95th percentile and additionally 20 mg zinc from food supplements will lead to an intake close to the tolerable upper intake level established by IOM for adults. For adolescents and child populations the maximum amounts are 15 and 5 mg for 13- and 9-year-olds, respectively. For 2 and 4-yearolds, P95 from intake of zinc from food alone exceeds the UL.

Assessment of Dietary Intake of Vitamin C and Calcium in the Norwegian Population

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of vitamin C and calcium in the Norwegian population. VKM has also conducted scenario estimations to illustrate the consequences of amending maximum limits for vitamin C (to 100, 300, 500, 600, 800 or 1000 mg/day) and calcium (to 800, 1200 or 2000 mg/day) in food supplements. Vitamin C: Vitamin C refers to both ascorbic acid and dehydroascorbic acid. Scurvy is the manifestation of vitamin C deficiency which is preventable by a daily intake of 5-10 mg/day. Fruits, berries and vegetables are important food sources of vitamin C and especially citrus fruit are important contributors. The Norwegian recommendation for dietary intake of vitamin C is 75 mg/day for adults (Helsedirektoratet, 2014). Vitamin C is absorbed from the intestine by an active process that is dose dependent. The bioavailability is at least 80% for doses up to 100 mg, 70% for doses of 200-500 mg and less than 50% for doses exceeding 1000 mg. Intestinal discomfort and diarrhea have been reported by persons using large doses (>1000 mg/day) of vitamin C supplementation. In 2000 the Institute of Medicine (IOM) in the USA proposed a tolerable upper intake level (UL) for vitamin C intake from food and supplements of 2000 mg/day for adults. ULs for children and adolescents were extrapolated based on body weight; 400 mg for children 1-3 years, 650 mg/day for children 4-8 years, 1200 mg/day for 9-13 years old adolescents, 1800 mg/day for 14-18 years old (IOM, 2000). In the assessment of vitamin C, VKM uses the Norwegian recommendations for intakes (Helsedirektoratet, 2014), and the acceptable dose for supplemental vitamin C from EFSA (2004) for adults and the tolerable upper intake levels established by the IOM (2000) for children and adolescents. Daily intakes of vitamin C from diet and supplements are estimated from nationwide dietary surveys performed in selected age groups: Adults 18-70 years, adolescents aged 13 years, and children aged 2, 4, and 9 years. Not all age-groups in the Norwegian population reach the recommended intake of vitamin C. At the 5th percentile, only 13-year-olds have an intake of vitamin C from food alone above the recommendations. At the 25th percentile, all age groups except adults have a vitamin C intake from food alone at or above the recommendations. At the 40th percentile, adults reach the recommended intake of vitamin C. The whole population would reach the recommended dietary intake with supplementation of 100 mg vitamin C per day. All the alternative maximum limits for vitamin C in food supplements listed in the terms of reference from NFSA (100, 300, 500, 600, 800 or 1000 mg/day) will be within the acceptable dose for supplemental vitamin C suggested by EFSA (2004) for adults. None of the alternative maximum limits for vitamin C in food supplements listed in the terms of reference (100, 300, 500, 600, 800 or 1000 mg/day) leads to exceedance of the tolerable upper intake levels established by IOM in adults, 13- year-olds or 9-year-olds, even with intakes from food at the 95th percentile. However, the tolerable upper intake level proposed by the IOM will be exceeded for 4-year-old children at supplemental doses above 500 mg vitamin C per day, and for 2-year-old children at doses higher than 100 mg/day. Calcium: Calcium is the most abundant mineral in the body and constitutes approximately 1200 g and 1400 g in adult women and men, respectively. More than 99% of the calcium in the body is bound to hydroxyapatite in bone and tooth enamel. Calcium is crucial for many bodily functions such as cell signalling, coagulation, muscular contraction, and neural transmission as well as skeletal integrity. Milk and dairy products are the main dietary sources of calcium, but foods such as fish, pulses, nuts, seeds (especially millet) and green vegetables may contribute to the total intake. The Norwegian recommendation for dietary intake of calcium is 800 mg/day for adults. The bioavailability of calcium is dependent on the amount of calcium ingested as well as the individual’s vitamin D status and physiological needs, like e.g. growth and pregnancy. Adverse effects of excessive calcium intake include symptoms of hypercalcaemia such as e.g. anorexia, weight loss, polyuria, heart arrhythmias, fatigue and soft tissue calcification (Jones, 2008 in IOM, 2011), deterioration of kidney function, kidney stone formation, the milk-alkali syndrome and vascular calcification. In 2012 the European Food Safety Authority (EFSA) established a tolerable upper intake level (UL) for calcium at 2500 mg/day from food and supplements for adults. No UL was set for children and adolescents. In 2011, IOM established a UL for 1-8 years old children to 2500 mg/day and 3000 mg/day for 9-18 years old children and adolescents (IOM, 2011). VKM however suggests that the UL established for adults by EFSA (2012) is used for the purpose of this VKM opinion also for children and adolescents, as the ULs from IOM for children and adolescents are considered to be high. In the assessment of calcium, VKM uses the Norwegian recommendations for intakes (Helsedirektoratet, 2014) and the tolerable upper intake levels established by the European Food Safety Authority for adults (includes both foods and supplements) (EFSA, 2012). Daily intakes of calcium from diet and supplements are estimated from nationwide dietary surveys performed in selected age groups: Adults 18-70 years, adolescents aged 13 years, and children aged 2, 4, and 9 years. Not all age groups in the Norwegian population reach the recommended intake of calcium. At the 5th percentile, no age groups fulfil the recommended daily intakes of calcium from food alone, and in the 50th percentile the 13-year-olds did not reach the recommended intake for calcium from food alone. At approximately the 65th percentile, the 13-year-olds reach the recommended intake for calcium. The whole population would reach the recommended dietary intake with supplementation of 800 mg calcium per day. For calcium, three alternative maximum limits were listed in the terms of reference (800, 1200 and 2000 mg/day). In the scenarios for high intakes of calcium, a dietary calcium intake at the 95th percentile and additionally 800 mg calcium from food supplements, will lead to an intake close to the tolerable upper intake level established by EFSA for the adult population, and supplements with 1200 or 2000 mg calcium per day will lead to exceedance of the tolerable upper intake level in adults. Children and adolescents with a dietary intake at the 95th percentile and additionally 2000 mg calcium from food supplements, will all exceed the UL suggested for adults by EFSA in 2012. All age groups except 4-year-olds will also exceed the UL with 1200 mg supplemental calcium. With 800 mg supplemental calcium 13-year-old adolescents, 9-year-old, 4 year-old and 2-year-old children will not exceed the suggested UL.

Assessment of Dietary Intake of Potassium in Relation to Upper Guidance Level

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of potassium in the Norwegian population. VKM has also evaluated the consequences of amending the existing maximum limit for potassium at 1000 mg/day to 300, 2000 or 3000 mg/day in food supplements. Potassium is an essential mineral to humans and is important as the osmotically active element inside the cells, whereas sodium and chloride are the main elements outside the cells. The enzyme Na+/K+ -ATPase pumps potassium ions into the cells and sodium ions out of the cells and helps keep the intracellular potassium concentration about 30 times higher than that of plasma and interstitial fluids. The plasma potassium concentration is maintained within narrow limits (3.5 to 5.0 mmol/L) by multiple mechanisms making up the potassium homeostasis. The strict regulation is essential for a broad array of important physiological processes, like the resting cellular membrane potential and the transmission action in neuronal, muscular and cardiac tissue. Potassium is also important for hormone secretion, vascular tone, systemic blood pressure control, gastrointestinal motility, acid-base balance, glucose and insulin metabolism, mineralocorticoid action, renal concentration ability and fluid and electrolyte balance. Both hypo- and hyperkalaemia result in increased mortality. The EFSA recommendations (2016) for adequate intake (AI) of potassium is 3500 mg/day for adults, both sexes, whereas the recommended intake (RI) in the Nordic Nutrition recommendations (2012) is 3500 mg/day for men and 3100 mg/day for women. Tolerable upper intake levels have not been established for potassium from food, because intake from food has not caused adverse health effects in the healthy population. In children the renal function rapidly reaches the normal adult level in early childhood and no concern about high intake of potassium from food has been put forward. Potassium chloride supplement has, however, resulted in hyperkalaemia and case reports have described heart failure and cardiac arrest at plasma concentrations above 5.5 mmol/L and doses over 6.5 - 6.8 g supplementary potassium per day. VKM proposes to use 3000 mg/day of potassium as an upper guidance level for daily dose of supplemental potassium in adults since this dose has not been shown to cause hyperkalaemia or heart failure, and has not resulted in gastrointestinal lesions. The proposed upper guidance level for adults extrapolated for body weights corresponds to 2630 mg/day for adolescents 14 to <18 years, 1860 mg/day for children 10 to < 14 years and 990 mg/day for children 3 to 10 years. For vulnerable groups all doses of potassium supplementation could lead to hyperkalaemia. Vulnerable groups such as persons with impaired kidney function and elderly have been estimated to comprise 15-20% of the population of Norway. However, most of the vulnerable individuals will be aware of the condition and be under medical supervision. Accordingly, all the evaluated doses from NFSA (300, 1000, 2000 and 3000 mg/day of potassium in food supplements are at or below the suggested upper guidance level for supplemental potassium for adults (>18 years). In adolescents 14 to <18 years, the supplemental doses of 300, 1000 and 2000 mg/day are below the suggested upper guidance level. For the younger age groups, only 300 mg/day is below the suggested upper guidance level for supplemental potassium.

Assessment of Dietary Intake of Phosphorus in Relation to Tolerable Upper Intake Levels

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of phosphorus in the Norwegian population. VKM has also conducted scenario calculations to illustrate the consequences of amending maximum limits for phosphorus (to 1000, 2000 or 2500 mg/day) in food supplements. Phosphorus is an essential nutrient and is involved in many physiological processes, such as in the cell’s energy cycle, in regulation of the body’s acid-base balance, as a component of the cell structure, in cell regulation and signalling, and in the mineralisation of bones and teeth. In the human body, phosphorus is present in different forms. Serum contains mainly inorganic phosphates (Pi) (dihydrogen and monohydrogen phosphate), bone contains phosphorus largely in the form of hydroxyapatite, whereas the soft tissues and extracellular fluids contain organic phosphates in complex with carbohydrates, lipids and proteins. Phosphorus is the main mineral constituent of bones. About 85% of the body’s phosphorus is in bones and teeth, and together with calcium account for around 80-90% of bone composition. The remaining 15% of the body’s phosphorus is essential in functions ranging from the transfer of genetic information to energy utilisation. Phosphorus is a structural component of the nucleic acids DNA and RNA and thus involved in the storage and transmission of genetic material. It is an essential component of phospholipids (e.g. phosphatidylcholine) that form all membrane bilayers throughout the body. Phosphorus is also an essential component of adenosine triphosphate (ATP), the body’s key energy source. Currently there is no reliable biomarker of phosphorus status, and serum phosphorus increases for a short period after ingestion of a meal and then decreases and remains within a relatively narrow range as a result of homeostatic mechanisms. The EFSA recommendations (2015) for adequate intake (AI) of phosphorus is 550 mg/day for adults, both sexes, whereas the recommended intake (RI) in the Nordic Nutrition Recommendations (2012) is 600 mg/day. Adolescents have a higher requirement of phosphorous because of bone accretion (640 mg/day EFSA and 700 mg/day NNR). EFSA (2005) concluded that the available data were not sufficient to establish a tolerable upper level for phosphorus, however, data indicate that normal healthy individuals can tolerate phosphorus intakes up to 3000 mg/day. EFSA advised supplemental intake not to exceed 750 mg/day, because mild gastrointestinal symptoms have been reported when this dose was increased. EFSA gave no UL suggestions for children, lactating or pregnant women, while Institute of Medicine set a UL for total intake of phosphorous for children at 3000 mg/day and 4000 mg/day for adolescents and adults and 3500 mg/day for lactating women. In accordance with EFSA (2005), VKM suggests to use 3000 mg/day as a provisional UL for total intake of phosphorous for adults, and suggests 750 mg/day as an upper level for supplements. Because of lack of data no provisional ULs are set for adolescents or children. Accordingly, all the suggested doses from NFSA (1000, 2000 and 2500 mg/day) in supplements exceed 750 mg/day, the suggested UL for supplemental phosphorus for adults.

Assessment of Copper Intake in Relation to Tolerable Upper Intake Levels

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of copper in the Norwegian population in relation to tolerable upper intake levels (ULs). VKM has also conducted scenario calculations to illustrate the consequences of amending maximum limits for copper to 1, 2, or 3, mg/day in food supplements. The existing maximum limit is 4 mg/day. Copper is a micronutrient essential for energy utilisation, brain function (neurotransmitter regulation), soft tissue and bone (collagen synthesis), nutrient metabolism (especially iron) and antioxidant defence against free radicals. Foods account for 90% or more of copper intake in adults when the copper content in drinking water is low (< 0.1 mg/L). If the copper content is higher (> 1-2 mg/L), water may account for up to 50% of total intake (EFSA, 2015). We reviewed four risk assessments undertaken by the Institute of Medicine (IOM), Scientific Committee on Food (SCF), Expert Committee on Vitamins and Minerals (EVM), and the Nordic Nutrition Recommendations (NNR). Liver damage was selected as a critical endpoint from which to derive a UL because it was judged to be the most reliable marker and consequence of a long-term chronic high copper intake. However, copper-related liver damage is observed almost exclusively in patients with genetic predispositions of copper accumulation. VKM suggest to use the UL at 5 mg/day (NNR Project Group, 2012; SCF, 2003). This UL was derived from human studies.In the light of the evidence, SCF decided that an uncertainty factor (UF) of 2 was adequate to allow for potential variability within the normal population, whereas the Institute of Medicine (IOM) applied a UF of 1. VKM find the higher UF suitable because human data is limited, the uncertainty of the copper content of drinking water and the potential severe and irreversible adverse effects. According to the scenario calculations, adults and 13-year-olds with high copper intakes from regular foods (95 th percentile) will exceed the ULs with supplemental copper at doses of 3 mg/day or higher. 9-year-old children will exceed the UL with use of 2 mg supplemental copper per day. For younger children the ULs will be exceeded in more than 5% without adding supplemental copper. In our calculations, copper from drinking water is not included. Copper concentrations in annual samples from waterworks are in general below 0.1 mg/L (Nordheim et al., 2016).

Assessment of Intake of Nicotinic Acid and Nicotinamide in Relation to Tolerable Upper Intake Levels

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the intake of niacin in the Norwegian population. NFSA has also requested that VKM conduct scenario calculations to illustrate the consequences of establishing separate maximum limits for nicotinic acid (1, 4, 8 or 10 mg/day) and nicotinamide (100, 500, 700 or 900 mg/day) in food supplements, by assessing these scenarios against existing tolerable upper intake levels (ULs). The current maximum limit for niacin added to food supplements is 32 mg/day, including nicotinic acid, nicotinamide and inositol hexanicotinate. The term niacin (vitamin B3) comprises the two main water-soluble forms nicotinic acid and nicotinamide (niacinamide). The human body can get niacin from the diet or synthesise it from the essential amino acid tryptophan. Dietary intakes are expressed as milligram niacin equivalents (NEs), which correspond to 1 mg of pure niacin or 60 mg of tryptophan. In the body, niacin primarily functions as a component of the coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate) which are present in all cells. These coenzymes play essential roles for the functioning of a wide range of enzymes involved in the metabolism of carbohydrates, amino acids and fat. In addition to its function in coenzymes, niacin is involved in DNA repair and gene stability. Niacin has a half-life of 20-40 minutes in the human body. Late symptoms of severe niacin deficiency (pellagra) include fatigue, headache, apathy, depression, memory loss, dementia, pigmented skin rash after sun exposure, bright red tongue, vomiting, diarrhoea, and constipation. Flushing (burning and itching of the face, arms and chest) and stomach irritation are the main side effects of moderately high supplemental intake of nicotinic acid (>35 mg/day). Long-term use of high doses (≥3000 mg/day) of nicotinic acid as a cholesterol-lowering drug can also be toxic to the liver. Nicotinamide, however, does not have these effects. In general, the risk of nicotinamide toxicity appears to be quite low. VKM proposes to adopt the ULs of nicotinic acid and nicotinamide set by the Scientific Committee for Food Safety (SCF) in 2002, which are based on one human dose-response study (nicotinic acid) and several human dose-response studies (nicotinamide), respectively. Hence, the UL for supplemental nicotinic acid is suggested to 10 mg/day for adults and the UL for supplemental nicotinamide to 900 mg/day for adults. The ULs for children and adolescents have been derived on the basis of their body weights. The ULs set for nicotinic acid and nicotinamide concern only intake from supplements since intake of nicotinic acid and nicotinamide from regular foods is considered to be without risk of negative health effects. Therefore, VKM has not conducted or evaluated scenarios with intake from both diet and the separated new maximum limits for nicotinic acid and nicotinamide in food supplements suggested by NFSA. Dietary calculations, however, have been performed for niacin intakes (includes both nicotinic acid and nicotinamide) in various percentiles (P5, P25, mean, P50, P75 and P95) in children (2-, 4- and 9-year-olds), adolescents (13-year-olds) and adults as background information. Mean and median intakes of niacin from the diet alone are above or at the recommended intakes for all age groups. Because UL for supplemental nicotinic acid is 10 mg/day for adults, none of the suggested maximum limits in food supplements (1, 4, 8, or 10 mg/day) will lead to exceedance of this UL in adults. In 13-year-olds and 9-year-olds, supplements with 8 mg nicotinic acid per day will lead to exceedance of UL, and in 4-year-olds and 2-year-olds supplementation of 4 mg nicotinic acid per day will lead to exceedance of the UL for nicotinic acid. Because UL for supplemental nicotinamide is 900 mg/day for adults, none of the suggested maximum limits in food supplements (100, 500, 700 or 900 mg/day) will lead to exceedance of UL in adults. In 13-year-olds, supplements with 700 mg nicotinamide per day will lead to exceedance of UL. In 9-year-olds, 4-year-olds and 2-year-olds, supplementation of 500 mg nicotinamide per day will lead to exceedance of the UL for nicotinic acid.

Risk Assessment of Dietary Exposure to Acrylamide in the Norwegian Population

Request from the Norwegian Food Safety Authority The Norwegian Food Safety Authority (NFSA) requested the Norwegian Scientific Committee for Food Safety (VKM) to assess whether Norwegians in general or subgroups in the population could be expected to have different dietary exposure to acrylamide than reported for other European population groups, and if found to be different to calculate their exposure. Furthermore, VKM was asked to identify food categories with a high potential to increase acrylamide exposure; both for the whole population and for specific groups. Finally, VKM was asked to characterise the risk of acrylamide exposure to the Norwegian population compared to the rest of the European population. The Norwegian Food Safety Authority intends to use this risk assessment as a basis for the Norwegian contribution to the ongoing legislative work in the EU and to consider the necessity to adjust the existing national dietary advices or to issue new ones. How VKM has addressed the request VKM appointed a working group consisting of members of the Panel on Contaminants to answer the request. The Panel on Contaminants has reviewed and revised the draft prepared by the working group and finally approved the risk assessment on dietary acrylamide exposure in the Norwegian population. What acrylamide is and its toxicity to humans Acrylamide is a water-soluble organic chemical formed in carbohydrate-rich foods from naturally present carbohydrates and amino acids during cooking or other heat processing at temperatures above 120°C. Acrylamide is a widely used industrial chemical and is also formed in tobacco smoke. Acrylamide is known to be neurotoxic in humans and is classified as a probable human carcinogen. Concerns about exposure to acrylamide in the general population arose in 2002 when it was discovered in heat-treated foods. Dietary acrylamide exposure in Europe and Norway Dietary acrylamide exposure has been assessed by combining food consumption data and acrylamide concentration data and by biological markers of exposure both in Norway and different European countries. In the EFSA 2015 Scientific Opinion on acrylamide in food, chronic dietary exposure was calculated for 61,338 individuals from 28 surveys and 17 different European countries covering the following age groups: infants (<1 year old), toddlers (≥1 year to <3 years old), other children (≥3 years to <10 years old), adolescents (≥10 years to <18 years old), adults (≥18 years to <65 years old), elderly (≥65 years to <75 years old) and very elderly (≥75 years old). The estimation of human exposure to acrylamide revealed that infants, toddlers and other children were the most exposed groups, but EFSA concluded that dietary acrylamide represents a health concern for all age groups. In previous Norwegian studies reporting dietary acrylamide exposure, the mean and median exposure in adolescents and adults were in the range of 0.3-0.5 μg/kg bw per day. These estimates are in the same range as the mean daily exposures estimated by EFSA for adolescents (0.4-0.9 μg/kg bw) and adults (0.4-0.5 μg/kg bw). Taking into consideration the results from previous exposure estimates and knowledge about food consumption patterns in recent consumption surveys in Norway, VKM concludes that Norwegian adults, adolescents and children older than three years of age are not likely to have a different exposure to acrylamide than corresponding age groups in other European countries. VKM therefore decided not to perform a new exposure assessment in these age groups. No previous studies in Norway have assessed acrylamide exposure in infants and children less than three years of age. Information from national and European dietary surveys shows that Norwegian 1-year-olds, but not 2-year-olds, have higher consumption of infant porridge than other European toddlers. VKM therefore decided to conduct a full exposure estimate in 1-year-old toddlers. The comparison of data on acrylamide occurrence in food reported by EFSA (2015) and in foods sampled in Norway showed that acrylamide concentrations in the main food categories do not differ essentially, with the exception of three categories. The category “Potato crisps and snacks” has higher acrylamide concentrations in Norwegian samples than in those reported by EFSA, while the categories “Baby foods, other than cereal-based” and “Processed cereal-based baby food” (i.e. infant porridge) have lower concentrations in Norwegian samples than in those reported by EFSA. VKM considered that Norwegian analytical values were sufficient for exposure calculations if the concentrations were analysed in 16 samples or more. Infant porridge had 52 analysed samples and VKM considered that the brands sampled are representative for infant porridge on the Norwegian market. VKM calculated acrylamide exposure based on food consumption in Norwegian 1-year-olds by two approaches: one using EFSA concentration data only; and the other using Norwegian concentration data for food categories including 16 samples or more, and EFSA data for the remaining categories. Both approaches resulted in acrylamide exposures within the exposure range for toddlers reported by EFSA (2015). When using EFSA concentration data only the calculated daily exposure (mean: 1.6 μg/kg bw and P95: 3.2 μg/kg bw) is in the upper range calculated by EFSA for toddlers (mean range: 0.9-1.9 μg/kg bw, P95 range: 1.2-3.4 μg/kg bw). When using Norwegian concentration data for food categories including 16 Norwegian samples or more and EFSA data for the remaining categories, the calculated daily exposure (mean: 0.9 μg/kg bw, P95: 1.6 μg/kg bw) is in the lower range of what EFSA has calculated for toddlers. The dietary exposure for acrylamide in Norwegian 1-year-olds is within the same range as reported by EFSA for European toddlers. Although the acrylamide-concentration was lower in infant porridge (i.e. “Processed cereal-based baby food”) sampled in Norway than in those reported by EFSA, Norwegian 1-year-olds have higher consumption of infant porridge than European toddlers. In addition to infant porridge, soft bread is a major source of acrylamide in Norwegian 1-year-olds. Food categories with high potential to increase acrylamide exposure Baby food and soft bread contributed most to acrylamide exposure in the 1-year-olds, while food items contributing the most to acrylamide exposure in adults are fried potato products, coffee, biscuits, crackers and crisp breads, and soft bread. Previous Norwegian studies and EFSA (2015) showed that in all populations groups except toddlers, ‘fried potato products’ is a food group with high potential to increase acrylamide exposure. Acrylamide is also contributed by food items commonly consumed such as coffee and bread, and this is of concern in Norway as well as in the rest of Europe. The EFSA risk assessment included exposure scenarios addressing the potential impact of home-cooking habits, locations of consumption, and preferences for particular food products. These scenarios showed that food preparation, and particularly conditions of potato frying, resulted in large variations and a possible increase of acrylamide exposure by as much as 80%. VKM considers that these scenarios carried out by EFSA are equally relevant for the Norwegian population. The temperature and browning of fried potato products will have a considerable impact on the exposure to acrylamide. VKM calculated three simplified scenarios to illustrate the influence of consumption of particular food items on acrylamide exposure. These scenarios confirmed that potato crisps, French Fries and coffee are food items with high potential to increase acrylamide exposure. Risk characterisation of dietary acrylamide exposure in Norway VKM used the same reference points as EFSA (2015), and calculated Margin of Exposures (MOEs) for assessing health risk. MOE is the ratio between a reference value and the estimated dietary exposure. The MOE approach provides an indication of the level of safety but it does not quantify the risk as such. For non-neoplastic effects, EFSA used a BMDL10 value of 0.43 mg/kg bw/day as the reference point based on animal studies of neurotoxicity, and considered a substance-specific MOE of 125 or above as a sufficient safety margin for no health concern. For neoplastic effects, EFSA used a BMDL10 value of 0.17 mg/kg bw/day as the reference point based on animal studies, and taking into account overall uncertainties in the interpretation, EFSA concluded that a MOE of 10 000 or higher would be of low concern for public health. The EFSA risk assessment concluded that the MOEs for non-neoplastic effects were above 125 for all age groups indicating no health concern, whereas the MOEs for non-neoplastic effects were substantially lower than 10 000, indicating a health concern for all age groups. The dietary acrylamide exposure in Norwegian adolescent and adults reported in previous studies were within the range calculated by EFSA for these age groups. VKM therefore concludes that the resulting MOEs for non-neoplastic and neoplastic effects of acrylamide for adolescent and adults will be similar to those calculated by EFSA. VKM calculated acrylamide exposure based on food consumption in Norwegian 1-year-olds by two approaches: one using EFSA concentration data only; and the other using Norwegian concentration data for food categories including 16 samples or more, and EFSA data for the remaining categories. Both approaches resulted in comparable MOEs. For both non-neoplastic and neoplastic effects, MOEs for 1-year-olds were similar to those reported in EFSA 2015. For non-neoplastic effects of dietary acrylamide exposure, VKM reached the same conclusion as EFSA, which is that the MOEs across all age groups indicate no health concern. For neoplastic effects of dietary acrylamide exposure, VKM reached the same conclusion as EFSA, whi

Risk Assessment of Dietary Cadmium Exposure in the Norwegian Population

Request from the Norwegian Food Safety Authority (NFSA): The Norwegian Food Safety Authority requested the Norwegian Scientific Committee for Food Safety (VKM) to evaluate whether Norwegians in general or subgroups in the population could be expected to have different dietary exposure to cadmium than reported for other European population groups. Furthermore, VKM was asked to assess the potential health risk of cadmium exposure from brown meat of crabs and to identify how much crab can be eaten by children and adults without exceedance of the tolerable intake for cadmium. Finally, VKM was asked to identify other particular food items which would lead to an added cadmium exposure in Norway. The Norwegian Food Safety Authority intends to use the risk assessment as a basis for the Norwegian contribution to the ongoing legislative work in the EU and to consider the necessity to adjust the existing national dietary advices or to issue new ones. How VKM has Addressed the Request: VKM appointed a working group consisting of members of the Panel on Contaminants to answer the request. The Panel on Contaminants has reviewed and revised the draft prepared by the working group and finally approved the risk assessment on dietary cadmium intake in the Norwegian population. What Cadmium is and Its Toxicity to Humans: Cadmium (Cd) is a heavy metal found as an environmental contaminant, both through natural occurrence and from industrial and agricultural sources. Humans are exposed to cadmium by food, water and air, with food as the most important source in non-smokers. Cadmium accumulates especially in the kidneys and in liver. The amount of cadmium in the body increases continuously during life until the age of about 6070 years, from which it levels off. The most well characterised chronic toxic effects resulting from cadmium exposure are on kidneys and bones. The tolerable weekly intake (TWI) of cadmium was in 2009 reduced by EFSA from 7 to 2.5 μg /kg body weight (bw). The new TWI established was based on human studies on the dose-response relationship between concentration of cadmium in urine and kidney function. Severe cadmium-induced damage in cells in the proximal kidney tubules is considered to be irreversible and results in the progressive deterioration of renal function, even after cessation of exposure. Long-term exceedance of the TWI is of concern as it can increase the risk of developing kidney disease in the population. Keeping the exposure below the TWI will ensure that the cadmium concentrations in the kidneys will not reach a critical level for reduced kidney function. Dietary Intakes in Europe and Norway, and Major Dietary Cadmium Sources: In 2012, EFSA estimated that the mean cadmium exposure from food in Europe was close to the TWI and exceeded the TWI in some population groups, like toddlers and other children. Previous exposure assessments in Europe and Scandinavia, including Norway, clearly show that cereal based food and root vegetables, particular potatoes, are the major dietary cadmium sources in the general population. These are, however, not the food groups with the highest cadmium concentrations. The highest concentrations have been found in offal, bivalve molluscs and crustaceans (e.g. crabs), and previous exposure assessments have shown that high consumption of such food can be associated with high cadmium exposure at the individual level. There is large variation at the individual level regarding consumption of particular food items (e.g. crab brown meat) that can be important contributors to cadmium exposure in addition to the exposure from the regular diet. VKM has compiled the available Norwegian data on cadmium concentrations in food, mainly from 2006 and onwards. Comparison of Norwegian and European occurrence data shows that the cadmium concentrations for the food categories and items in the two datasets are within a similar range. The exceptions are fish filet and fish products (dishes based on minced fish meat), in which the mean cadmium concentrations were higher in products on the European market than in fish from Norway. VKM has evaluated if there are national factors (geological factors, self-sufficiency rate, national occurrence data and food consumption habits) that would indicate that exposure in Norway is different from the rest of Europe. VKM has also evaluated available national and European data on concentrations of cadmium in blood and urine in relation to estimated dietary intakes. VKM concludes that it can be expected that cadmium exposure among adults in Norway is within the range previously identified by EFSA, and close to the exposure estimated for Sweden. VKM is of the opinion that long-term cadmium exposure above the TWI as result from the regular diet in adults is unlikely in Norway, but that exceedance might occur from the additional consumption of food items with high cadmium concentrations, in particular brown meat of crabs. In dietary exposure estimates from EFSA, toddlers and other children have mean cadmium exposure exceeding the TWI, due to their higher food consumption relative to the body weight. Based on this, VKM expects that the mean dietary cadmium exposure in toddlers and children may exceed the TWI also in Norway. Risk from Cadmium Intake from Particular Foods in Norway: Based on the mean concentrations of cadmium, VKM identified fish liver, bivalve molluscs and offal in addition to brown crab meat as particular food items that potentially can lead to added cadmium exposure in Norway. Since these particular food items are mainly eaten on a seasonal or non-regular basis, it was stipulated that the associated cadmium exposure would come in addition to the mean exposure from regularly eaten food. In scenario exposure assessments, VKM calculated how much crabs/fish liver that could be consumed by adults and adolescents in addition to the regular diet without exceeding the TWI. The mean dietary exposures in adults and adolescents calculated by EFSA in 2012 were used as the mean exposures from regularly eaten food. Since cadmium accumulates in the kidneys over time (decades), VKM is of the opinion that a short-term exceedance of the TWI (for some weeks or a few months) will not lead to adverse effects in the kidneys as long as the long-term exposure (for several months and years) is below the TWI. VKM therefore considers that the cadmium exposure from particular food items can be averaged over longer time-periods (for months and up to one year) than a week. Crabs and fish liver: The edible crab Cancer pagurus is found all along the Norwegian coast up to Vesterålen, whereas further north the occurrence is infrequent. Brown meat from crabs contains much higher concentrations of cadmium than any other food item commonly consumed in Norway, and has approximately 14 to 20-fold higher concentration of cadmium than white crab meat. The cadmium concentration in fish liver is about two-fold higher than in white meat from crabs caught south of Saltenfjorden. A large part of the Norwegian adult population report consumption of crabs or fish liver at least a few times a year, while a small fraction consume these particular food items more frequently. Consumption of brown meat from crabs and fish liver is, however, not common in most European regions and therefore not covered by the exposure estimates performed by EFSA. The dietary assessment method used in the recent Norwegian national food consumption survey in adults (two times 24h dietary recall) does not supply reliable information about consumption of foods that are not eaten on a daily basis. In order to estimate cadmium exposure from rarely eaten foods, VKM has calculated scenarios for the exposure to cadmium from consumption of crabs and fish liver. Scallops, oysters and offal: The cadmium concentrations in scallops and oysters are 2-3 fold higher than in white meat from crabs caught south of Saltenfjorden. Offal, in particular offal from game and sheep, contains much higher cadmium concentrations than the meat from the same species. However, consumption of offal, including offal from game, and bivalve molluscs is generally low in Norway, although high consumption in some population groups cannot be excluded. In contrast to Norway, consumption of offal and bivalve molluscs is more common in some European regions, and is therefore covered by the exposure estimates performed by EFSA. Scenarios for Cadmium Exposure from Crab or Fish Liver Consumption: Crabs and filled crab shells: Because of high cadmium levels in edible crabs (Cancer pagurus) north of Saltenfjorden up to Vesterålen, Norwegian Food Safety Authority has issued advice to avoid consumption of all parts of crabs caught in this area. The scenarios presented below are valid only for meat of crabs caught south of Saltenfjorden. Whole crabs contain a higher percentage of brown meat than commercially available filled crab shells, and this was taken into account in the scenarios. Scenarios of cadmium exposure from crab consumption indicate that adults can eat approximately one whole crab or two filled crab shells per month in addition to regular food without exceeding the TWI. Averaged over a year, this corresponds to 13.5 whole crabs or approximately 25 filled crab shells. If adults only eat white crab meat, they can consume white meat from approximately nine crabs per week, which corresponds to white meat from approximately 468 crabs per year. Adolescents can eat as little as approximately 0.3 whole crabs or 0.6 filled crab shells per month in addition to regular food without exceeding the TWI. Averaged over a year, this corresponds to 3-4 whole crabs per year or approximately 7 filled crab shells. If adolescents only eat white crab meat, they can consume white meat from about 2.5 crabs per week, which corresponds to white meat from approximately 129 crabs per year. Since a higher crab consumption than the acceptable range calculated in the scenarios ha

Assessment of Selenium Intake in Relation to Tolerable Upper Intake Levels

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), evaluated the intake of selenium in the Norwegian population. VKM has also conducted scenario calculations to illustrate the consequences of amending maximum limits for selenium to 50, 150 or 200 μg/day in food supplements. The existing maximum limit is 100 μg/day. Selenium is a cofactor for enzymes and proteins with vital importance in antioxidant defence, thyroid hormone and insulin function and regulation of cell growth. We reviewed four risk assessments undertaken by the Institute of Medicine (IOM), Scientific Committee on Food (SCF), Expert Committee on Vitamins and Minerals (EVM), and the Nordic Nutrition Recommendations (NNR). Because of limited evidence from human studies and due to the selection of a high uncertainty factor (UF), we decided to use the tolerable upper intake levels (ULs) set by the SCF (2000) and later adopted by NNR (2012). Early signs of selenium toxicity are a garlic breath and a metallic taste. Severe selenosis results in fast hair loss and brittle nails, as well as other gastrointestinal symptoms such as nausea, vomiting, diarrhea, fatigue, irritability, and rash. Acute selenium intoxication and chronical overexposure may affect the nervous system and result in nerve damage. The SCF established a UL for selenium at 300 μg/day for adults, including pregnant and lactating women. This UL was based on a no observed adverse effect level (NOAEL) of 850 μg/day for clinical selenosis applying a UF of 3, and was supported by three studies reporting no adverse effects for selenium intake between about 200 and 500 μg/day. As there were no data to derive specific ULs for children, the SCF (2000) extrapolated the UL from adults to children based on reference body weights. The proposed UL values for children and adolescents ranged from 60 μg/day (1–3 years) to 250 μg selenium/day (15–17 years). According to the scenario estimations in adults, the dietary selenium intake at the 95th percentile and additionally 150 μg selenium from food supplements will be below the UL while 200 μg selenium from food supplements will lead to exceedance of the UL for adults. For 13- and 9-year-olds, supplemental doses of 100 and 50 μg selenium per day, respectively, do not lead to exceedance of the ULs in these age groups. For 2- and 4-year-olds, all the suggested doses in food supplements will lead to exceedance of the ULs.

Benefit-risk Assessment of Fish and Fish Products in the Norwegian Diet – An Update.

Request from the Norwegian Food Safety Authority (NFSA) In September 2013, the Norwegian Food Safety Authority requested VKM to update relevant parts of the benefit-risk assessment of fish in the Norwegian diet published by VKM in 2006. The background for the request was new knowledge and data on the content of some nutrients and contaminants both for wild and farmed fish since 2006. The proportion of vegetable ingredients used in farmed fish feed has in recent years increased, and new national dietary surveys for adults and children have been conducted. The Norwegian Food Safety Authority referred to VKM’s report from 2006, which pointed out that the positive impact of fish consumption on public health was especially due to the content of polyunsaturated fatty acids and vitamin D in fish. Further, VKM concluded that the contaminants that could pose a potential risk to public health through fish consumption mainly were methylmercury, dioxins and dioxin-like PCBs (dl-PCBs). The request included a reassessment of fish consumption in Norway with focus on specific nutrients; n-3 fatty acids (eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), vitamin D, and the minerals iodine and selenium, and on specific contaminants; mercury, dioxins and dl-PCBs. VKM was asked to address the main changes in the use of raw materials in farmed fish feed and how these affect the levels of nutrients, mercury, dioxins and dl-PCBs and in fish feed. Further, VKM was asked to address to what extent levels of nutrients and contaminants in fish have changed since 2006, to describe these changes and estimate the human intake of the substances in question on the basis of recent dietary data. VKM was also requested to consider the benefits of eating fish with regard to the intake of nutrients and the risks associated with the intake of mercury, dioxins and dl-PCBs and comment on whether this change the conclusions from the report in 2006. Additionally, on the basis of updated knowledge, VKM was asked to comment whether other substances, like pesticide and residues of veterinary medicinal products, could affect the conclusions with regard to the impact on public health. The Norwegian Food Safety Authority and the Directorate of Health will use the updated assessment as a basis for public recommendations concerning the consumption of fish and fish products. How VKM has Addressed the Request The VKM appointed a working group consisting of VKM members and external experts to answer the request. Several of the scientific panels of VKM reviewed the report during its preparation. The Scientific Steering Committee of VKM has given their final assessment and approval of the current report. In the current report, VKM has mainly used data from national surveillance and monitoring programs for nutrient and contaminant concentrations in fish feed, farmed fish and wild caught fish, but occurrence data have also been derived from peer reviewed articles. VKM has estimated fish consumption in three population groups (2-year-olds, adults and pregnant women). The estimated fish consumption was compared to national dietary guidelines. To assess health effects of fish consumption, the current estimated fish intakes were also compared with assessments done by recognised international bodies and results from epidemiological studies addressing possible associations between fish consumption and specific health outcomes. Literature searches were done to identify relevant epidemiological studies. VKM has not systematically assessed reviews or meta-analyses nor individual studies for weight of evidence, but merely summarised the studies retrieved from the literature search. It was considered being beyond the scope of this assessment to review individual studies included in reviews or meta-analyses. Furthermore, based on current fish consumption in the various population groups, intake of nutrients and exposure to contaminants from fish were estimated. For benefit characterisation of the specific nutrients the estimated nutrient intake was compared with national recommendations of nutrients intake and for EPA and DHA a comparison was also done with European recommendations. For risk characterization of contaminant exposure from fish, VKM used health based guidance values set by international risk assessment bodies (WHO, EFSA). VKM noted that the request from NFSA was restricted to fish, whereas the VKM report in 2006 included both fish and other seafood. VKM focused on specific nutrients and contaminants as requested by the NFSA. In addition, VKM also commented on other substances that could affect the risk assessment, such as residues of veterinary medicinal products including residues of antibiotics, new contaminants from fish feed like the pesticide endosulfan, polycyclic aromatic hydrocarbons (PAHs), mycotoxins, the synthetic antioxidants ethoxyquin, butylhydroxyanisole (BHA) and butylhydroxytoluene (BHT), as well as environmental contaminants like brominated flame retardants and perfluorated organic compounds Background In the Norwegian diet fish is important source of well-balanced proteins, and important nutrients such as EPA and DHA, vitamin D, iodine and selenium. On the other hand, fish is also a source of exposure to chemical contaminants like dioxins, PCBs and mercury. Over the last 10 years there has been a great change in raw materials used in fish feeds, and in 2013 terrestrial plant proteins and vegetable oils accounted for 70% of the feed. The changes in concentrations of nutrients and contaminants in fish feed for farmed Atlantic salmon and trout are reflected in changed concentrations and compositions of the same nutrients and contaminants in the farmed fish fillet. The current national dietary guideline is to eat fish as dinner meals 2-3 times per week for all age groups, representing 300-450 g fish per week for adults, including at least 200 g fatty fish, such as salmon, trout, mackerel and herring. Fish is also recommended as bread spread. Further, a daily supplement of vitamin D to infants from 4 weeks of age is recommended, and if this supplement is taken as cod liver oil it will in addition ensure an adequate supply of EPA and DHA. The present benefit-risk assessment is comprised of three elements, i.e. benefit assessment, risk assessment and benefit-risk comparison. This methodology is in accordance with the guidance given by EFSA in 2010. Fish Consumption in Norway and Comparison with National Dietary Guidelines VKM has used information about fish consumption from more recent national dietary surveys among 2-year-olds (Småbarnskost 2007) and adults at 18-70 years of age (Norkost 3, 2010/2011), as well as information for pregnant women who answered the Norwegian Mother and Child Cohort Study (MoBa2, 2002-2008) food frequency questionnaire. The national food consumption survey Ungkost 2000, which covers the age groups 4-, 9-, and 13-year-old children, was considered too old to be used and it is therefore not known if their fish consumption patterns have changed, neither in amount consumed nor type of fish consumed. Even though there are methodological differences between the dietary surveys used in 2006 and 2014, the amount of fish consumed appears to be unchanged for all population groups. Furthermore, in 2014, lean fish and fatty fish contribute with about 60 and 40 percent, respectively, of the total fish consumption, which is similar to 2006. Given a portion size of 150 g fish, the average adult eats fish equivalent to 2-3 dinner servings per week and the average pregnant woman eats fish equivalent to 1-2 dinner servings per week, while the average two-year-old eats fish equivalent to 1-2 dinner servings per week given a portion size of 75 g. The table below describes fish intake in the selected populations. Fish consumption (expressed as raw fish), mean grams (g) per week in 2-year-olds (Småbarnskost 2007, n=1674), adults (Norkost 3, n=1787) and pregnant women (MoBa, n=86277) Population groups Mean fish consumption g/week Fish roe Fish, total Lean fish (≤ 5% fat) Fatty fish (> 5% fat) and liver 2-year-olds 112 70 35 7 Adults 364 210 147 7 Pregnant women 217 126 77 14 VKM concludes that of the different population groups, only adults (18-70 years of age) with an average or higher fish consumption reach the national food based dietary guidelines for total fish consumption. Mean total fish consumption and fatty fish consumption in children (2-year-olds) and pregnant women, as well as the mean fatty fish consumption in adults are lower than recommended. In pregnant women and 2-year-olds, fish consumption is too low to meet the food based dietary guidelines Health Effects of Fish Consumption VKM is of the opinion that according to epidemiological studies, the net effects of the present average fish consumption in Norway for adults including pregnant women is beneficial for specific cardiovascular diseases (particularly cardiac mortality, but also with regard to ischaemic stroke, non-fatal coronary heart disease events, congestive heart failure and atrial fibrillation), as well as for optimal neurodevelopment of foetus and infants. Furthermore, VKM is of the opinion that those with fish consumption less than one dinner serving per week may miss these beneficial effects. The health benefit of fish consumption is reported from 1-2 dinner servings per week and up to 3-4 dinner servings per week. For higher fish intake per week, the limited number of consumers in epidemiological studies does not allow for drawing firm conclusions about the actual balance of risk and benefit. More knowledge is needed to reveal the beneficial mechanisms of fish consumption. Benefit Characterisation of Nutrients in Fish VKM is of the opinion that there has been minor or no changes of the composition and concentrations of nutrients in wild caught fish since 2006. Due to replacement of fish oil and fish protein with plant prote