EFSA: Potassium molybdate as a source of molybdenum added for nutritional purposes to food supplements
Following a request from the European Commission to the European Food Safety Authority (EFSA), the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on the safety of potassium molybdate, as a source of molybdenum, added for nutritional purposes in food supplements and on the bioavailability of molybdenum from this source.
The present opinion deals only with the safety of potassium molybdate, as a source of molybdenum, added for nutritional purposes in food supplements and with the bioavailability of molybdenum from this source. The safety of molybdenum itself, in terms of the amounts that may be consumed, is outside the remit of this Panel.
Sodium molybdate and ammonium molybdate are already listed in annexes of the Commission Directive 2002/46/EC, as substances which may be used in the manufacture of food supplements, and the Commission Directive 2001/15/EC, as substances that may be added for specific nutritional purposes in foods for particular nutritional uses.
According to the petitioner, potassium molybdate is intended to be used in supplements to provide an intake of 5-20 µg molybdenum/day (2 tablets), which is equivalent to 12-50 µg of potassium molybdate/day.
Based on an average dietary molybdenum intake in the range of 80-250 µg/day, the Panel estimated that consumption of an additional food supplement containing 20 µg molybdenum/day (the highest use level proposed by the petitioner) would result in a total anticipated dietary exposure between 100 and 270 µg molybdenum/day in an adult at the average level of dietary intake.
When the high dietary intake range of 96-500 µg/day molybdenum for the European population is considered, the consumption of a food supplement providing 20 µg/day would result in a total anticipated exposure of between 116 and 520 µg/day. The Panel notes that this molybdenum exposure would not exceed the Tolerable Upper Intake Level (UL) of 0.6 mg/day as established by the Scientific Committee for Food (SCF) in 2000 for adults.
The Panel considers that the use levels proposed by the petitioner (between 5 and 20 µg/day) would not exceed the ULs of 0.1 to 0.5 mg molybdenum/day defined by the SCF for children (1-17 years old). However, given the wide range of UL values established by the SCF based on age body weights, the Panel considers that in some cases these ULs could be exceeded when molybdenum intake from food is taken into account together with food supplementation.
Assuming a dietary intake range between 64-89 and 80-144 µg molybdenum/day for children between 1-3 and 4-17 years old, respectively, in addition to a daily consumption of an additional food supplement containing 20 µg molybdenum (the highest proposed use level by the petitioner), the Panel estimates total anticipated exposures between 84-109 and 100-164 µg molybdenum/day respectively. The Panel notes that the molybdenum exposure exceeds the UL of 0.1 mg/person/day as established by the SCF in 2000 for children between 1 and 3 years of age.
Assuming a high percentile dietary molybdenum intake of 199 µg/day for age group of 4-6 years old, the Panel estimates that a consumption of an additional food supplement containing 20 µg molybdenum (the highest proposed use level by the petitioner) would result in a total anticipated daily molybdenum intake of 219 µg molybdenum/day at the high level of dietary exposure. The Panel notes that this molybdenum exposure exceeds the ULs of 0.1 mg/person/day and 0.2 mg/person/day, as established by the SCF in 2000 for children between 1 and 6 years old, respectively.
Based on the highest proposed use level, an anticipated exposure to potassium from the food supplements is 16 µg/day. The Panel considered this amount as being negligible compared to the average daily dietary intake of potassium defined by EFSA in 2005, which ranges from 2.7-4 g/day.
No data on bioavailability were provided on the source, potassium molybdate itself. The Panel considers that due to its ionisation properties (pKa = 4), the non-ionized form of potassium molybdate should be absorbed by a diffusion process in the stomach. Potassium molybdate should also dissociate into its constituents, potassium and molybdate ions, in the small intestine. Accordingly, molybdenum from potassium molybdate should be bioavailable and absorbed in the same manner as from other soluble molybdates. Regarding other water-soluble sodium or ammonium molybdates, these compounds are readily taken up through the gastrointestinal tract. Following absorption, molybdates are distributed throughout the body with the highest levels generally found in the liver, kidneys, spleen, and bone. Biological half-life may vary from several hours in laboratory animals to as much as several weeks in humans.
No toxicity data were provided on the source, potassium molybdate, itself.
The toxicity of molybdates has been reviewed by several authorities including the SCF, and the UK Expert Group on Vitamins and Minerals (EVM). Overall these reviews indicate that the data documenting molybdenum toxicity in humans are limited. In studies conducted in a region of Armenia where levels of molybdenum in the soil are high, adults were found to have elevated plasma and urine concentrations of uric acid and gout-like symptoms. In these studies, the daily molybdenum intake for adults was estimated to be 10 15 mg.
In animals, acutely toxic oral doses of molybdenum result in severe gastrointestinal irritation with diarrhea, coma and death from cardiac failure. Subchronic and chronic oral exposures can result in growth retardation, anaemia, hypothyroidism, bone and joint deformities, sterility, liver and kidney abnormalities, and death. In rabbit, two separate subchronic toxicological studies (4 and 6 months respectively) of molybdates indicated differences in the No-Observable-Adverse-Effect-Level (NOAEL) for ammonium and sodium molybdates (0.5 and 23 mg/kg bw/day, respectively). Regarding reproductive toxicity, male sterility and embryotoxic effects of sodium molybdate were observed in rats, and in particularly reduced foetal weight gain, delayed histological development of foetal structures and increased fetal resorption. The NOAEL of this study was 0.9 mg molybdenum/kg bw/day for reproductive toxicity. This study in rats was considered pivotal by the SCF, in its opinion on the tolerable intake level of molybdenum.
There are no relevant studies of molybdenum or molybdate carcinogenicity in animals or humans. Regarding genotoxicity, both negative and positive responses on bacteria have been obtained with molybdates, as previously indicated by the SCF. Ammonium molybdate induced chromosome aberrations and sister-chromatid exchanges in human lymphocytes in vitro. Molybdenum trioxide but not ammonium molybdate induced chromosome damage in mouse bone marrow whereas dominant lethal mutations were induced in Drosophila exposed to ammonium molybdate. A study on the tolerable intake level of molybdenum, not available at the time of the SCF opinion was published, used the micronucleus assay in human lymphocytes. In this study, ammonium molybdate was more potent than sodium molybdate in inducing chromosome loss in cultured human lymphocytes. This study also assessed the genotoxicity of sodium molybdate in vivo by using the micronucleus assay in mouse bone marrow and the dominant lethal assay in mice, this study was used to assess the genotoxic effects of sodium molybdate in vivo. However, it provided a limited evidence of in vivo genotoxicity of this salt in mouse somatic and germ cells.
The Panel concludes that the use of potassium molybdate, as a source of molybdenum, added for nutritional purposes in food supplements at the proposed use levels, is of no safety concern provided the applicable UL for molybdenum established by the SCF is not exceeded.
The Panel notes that since the SCF adopted its opinion on molybdenum, new toxicological data have been made available on in vitro and in vivo genotoxicity of molybdenum that might need further investigation.