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EC number: 208-915-9 | CAS number: 546-93-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Exposure related observations in humans: other data
Administrative data
- Endpoint:
- exposure-related observations in humans: other data
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Well documented summary of data from a reliable source.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 001
- Report date:
- 2001
Materials and methods
- Type of study / information:
- This document is an official opinion of the SCF (Scientific Committee on Food of the European Commission) on derivation of a tolerable upper intake level of magnesium compounds.
- Endpoint addressed:
- repeated dose toxicity: oral
Test guideline
- Qualifier:
- no guideline required
- GLP compliance:
- no
Test material
- Reference substance name:
- Magnesium carbonate
- EC Number:
- 208-915-9
- EC Name:
- Magnesium carbonate
- Cas Number:
- 546-93-0
- Molecular formula:
- CH2O3.Mg
- IUPAC Name:
- magnesium carbonate
- Details on test material:
- This scientific opinion includes all easily dissociable magnesium salts (e.g. chloride or sulphate; included are compounds becoming readily dissociable after the reaction with gastric hydrochloric acid).
Constituent 1
Method
- Ethical approval:
- not applicable
- Details on study design:
- In this document, the different aspects of oral magnesium supplementation are critically reviewed on the basis of different chapters:
- Nutritional background
- Biological considerations
- Hazard identification
- Dose-response assessment
- Derivation of a tolerable upper intake level
- Characterisation of risk - Exposure assessment:
- measured
- Details on exposure:
- TYPE OF EXPOSURE: Only oral supplementation besides the "normal" dietary magnesium uptake are considered.
TYPE OF EXPOSURE MEASUREMENT: In the different studies reviewed in this opinion, biomonitoring was mainly conducted by magnesium quantification in blood and urine.
EXPOSURE LEVELS: Exposure levels taken into consideration for the assessment of adverse effects ranged from 180 mg Mg/day up to 1095 mg Mg/day. These values correspond to magnesium carbonate (MgCO3) levels of 624.5-3799 mg MgCO3/day.
EXPOSURE PERIOD: The exposure period of the different studies ranged from 1 to 72 weeks.
Results and discussion
- Results:
- Mild diarrhoea can be taken as the most sensitive non-desirable effect if Mg supplements are taken for nutritional purposes. However it must be kept in mind that adaptation of the bowel to higher oral Mg intake is known (Nadler et al., 1992; Stendig-Lindberg et al., 1993; Widman et al., 1993), that a mild laxative effect may be desirable (“four patients reported mild diarrhoea in the Mg group, and a similar number felt that their bowel function improved with less constipation”; Gullestadt et al., 1991), that mild laxative effects have been frequently observed also in the placebo groups (perhaps caused by taste adjusters, vehicles a.o.) (Sibai et al., 1989), that a given daily dose of Mg is better tolerated when it is divided into several portions, and finally that the galenic form (aqueous solution, capsules, tablets, etc.) may play a role. Data from the literature are summarized in Table 1 including children, pregnant women, tetanic, hypertensive and cardiac patients as well as volunteers. Papers were only considered when the presence or absence of “mild diarrhoea” was stated. Table 1 does not include Mg contained in food derived from plant or animal sources this being considered to be poorly dissociable (e.g. phytates).
As discussed, mild diarrhoea is the most sensitive non-desirable effect of orally administered easily dissociable magnesium salts. From the data presented in Table 1 one can conclude that mild diarrhoea occurs in a small percentage of adult subjects at oral doses of about 360/365 mg Mg per day, hence presenting the LOAEL.
No laxative effects have been observed in adult men and women -also during pregnancy and lactation- at doses up to 250 mg Mg per day. Therefore, this dose is considered as being the no-observed-adverse-effect level (NOAEL).
Toxic hypermagnesaemia, presenting e.g. with hypotension or muscular weakness, is only seen at oral Mg doses greater than 2,500 mg, i.e. doses exceeding the derived NOAEL by a factor of more than 10.
Any other information on results incl. tables
- Classen et al. (1986) Der Kinderarzt 17: 1565-1568.
- Schimatschek et al. (1997) Der Kinderarzt 28: 196-203.
- Schimatschek et al. (2001) Kinder- und Jugendmedizin [in press]
- Stendig-Lindberg et al. (1993) Magnesium Res 6: 155-163.
- Cappuccio et al. (1984) Brit Med J 291: 235-238.
- Plum-Wirell et al. (1994) Magnesium Res 7: 277-283.
- Spätlinget al.(1988) Brit J Obstet Gynaecol 95: 120-125.
- Gullestad et al. (1991) Magnes Trace Elem 10: 11-16.
- Rasmussen et al. (1989) Arch Int Med 149: 1050-1053.
- Ricci et al.(1991) Am J Obstet Gynecol165: 603-610.
- Bashir et al. (1993) Am J Cardiol 72: 1156-1162.
- Nadler et al. (1992) Diabetes Care 15: 835-841.
- Marken et al. (1989)Atherosclerosis 77: 37-42.
- Rueddel et al.(1990) Magnesium Res 3: 103-107.
- Spätling et al. (1998) Geburtsh u Frauenheilk 58: 561-565.
- Daly et al. (1990) Magnesium-Bull 12: 149-154.
- Spencer et al. (1994) J Am Coll Nutr 13: 485-492.
- Widman et al. (1993) Am J Hypertens 6: 41-45.
- Muehlbauer et al. (1991) Eur J Clin Pharmacol 40: 437-438.
Table 1: Mild diarrhoea induced by daily oral magnesium supplements
Total Mg Dose * [mg/day] |
Diarrhoea [n/total] |
Subjects |
|
Salt |
Weeks |
Ref. |
Included as supporting data |
Mean age [yr] (range) |
Gender |
||||||
180 |
0/130 |
5.3-17.4 |
M/F |
Asp. HCl# |
3 |
1 |
x |
245 |
0/112 |
8.1 (4-12) |
M/F |
Asp. HCl |
3 |
2 |
x |
245 |
0/181 |
4-12 |
M/F |
Asp. HCl |
3 |
3 |
|
250 |
0/31 |
58 |
F |
Hydroxide |
72 |
4 |
x |
365 |
0/17 |
52 (33-66) |
M/F |
Asp. HCl |
4 |
5 |
x |
365 |
0/39 |
40 (20-59) |
M/F |
Asp. HCl |
8 |
6 |
x |
365 |
1/278 |
28 (20-38) |
F |
Asp. HCl |
26 |
7 |
x |
365 |
4/17 |
71 (56-88) |
nd |
Lactate, Citrate |
6 |
8 |
x |
365 |
4/22 |
62 |
M/F |
Hydroxide |
12 |
9 |
x |
384 |
1/25 |
21 |
F |
Chloride |
4 |
10 |
x |
384 |
2/21 |
63 (42-73) |
M/F |
Chloride |
6 |
11 |
x |
400 |
2/20 |
46 (26-65) |
M/F |
Chloride, Oxide |
8 |
12 |
x |
476 |
18/50 |
30 (21-50) |
M/F |
Oxide |
8.5 |
13 |
|
480 |
2/12 |
16 (11-21) |
M/F |
Asp. HCl |
12 |
14 |
x |
480 |
2/37 |
28.5±4.5 |
F |
Asp. HCl |
4 |
15 |
x |
500 |
2/20 |
57 |
M/F |
Oxide |
12 |
16 |
x |
576 |
0/5 |
54 (38-75) |
M/F |
Oxide |
6 |
17 |
x |
970 |
Adaption |
50 |
M/F |
Hydroxide |
3x3 |
18 |
x |
1095 |
8/8 |
nd |
M/F |
Asp. HCl |
1 |
19 |
x |
* Referred to elemental Mg; nd = no data; M = males; F = females;#Asp. = aspartate.
References:
Applicant's summary and conclusion
- Conclusions:
- After oral supplementation with easily dissociable magnesium compounds, diarrhoea seems to be the most sensitive non-desirable effect. After reviewing 19 different human studies (including children, pregnant women, hypertensive and cardiac patients as well as volunteers) no laxative effects have been observed in adult men and women - also during pregnancy and lactation - at supplementary doses up to 250 mg Mg per day. Therefore, this dose is considered as being the no-observed-adverse-effect level (NOAEL). In a small percentage of adult subjects, mild diarrhoea occurs at oral doses of about 365 mg Mg per day, hence presenting the LOAEL.
These values, which are based on and apply to magnesium supplementation, i.e. on top of normal dietary intake of magnesium from its presence in food and bevereages, can be converted into the respective NOAEL and LOAEL values of 14.5 and 21.1 mg/kg bw/day for magnesium carbonate. - Executive summary:
This document is an official opinion of the SCF (Scientific Committee on Food of the European Commission) on derivation of a tolerable upper intake level of magnesium compounds, including all easily dissociable magnesium salts (also compounds becoming readily dissociable after the reaction with gastric hydrochloric acid). Different aspects of oral magnesium supplementation are critically reviewed on the basis of different chapters: Nutritional background, Biological considerations, Hazard identification, Dose-response assessment, Derivation of a tolerable upper intake level, and Characterisation of risk.
The review of 19 differentially conducted studies (including children, pregnant women, hypertensive and cardiac patients as well as volunteers) revealed that mild diarrhoea can be taken as the most sensitive non-desirable effect if Mg supplements are taken orally. From the data presented it can be concluded that mild diarrhoea occurs in a small percentage of adult subjects at supplementary oral doses of about 365 mg Mg per day, hence presenting the LOAEL. No laxative effects have been observed in adult men and women – also during pregnancy and lactation – at supplementary doses up to 250 mg Mg per day. Therefore, this dose is considered as being the no-observed-adverse-effect level (NOAEL). Toxic hypermagnesaemia, presenting e.g. with hypotension or muscular weakness, is only seen at oral Mg doses greater than 2,500 mg, i.e. doses exceeding the derived NOAEL by a factor of more than 10.
As all easily dissociable magnesium salts are included in this opinion, these values can also be applied to magnesium carbonate. It is therefore legitimate to derive a NOAEL/LOAEL for oral intake of magnesium carbonate from these data. Based on dose conversion of the magnesium data, the NOAEL and LOAEL for magnesium carbonate are 14.5 and 21.1 mg/kg bw/day, respectively.
The SCF UL of 250 mg Mg/day is based on and applies to magnesium supplementation, i.e. intake on top of normal dietary intake of magnesium from its presence in food and beverages. The NOAEL of 14.5 mg/kg bw/day for magnesium carbonate should therefore be viewed accordingly.
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