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Administrative data

biochemical or cellular interactions
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study conducted to good scientific principles.

Data source

Reference Type:
Effects of Magnesium Ions on Calcium and Phosphorous Metabolism
Clark I
Bibliographic source:
American Journal of Physiology, 214 (2): 348-356

Materials and methods

Principles of method if other than guideline:
The purpose of the study was to investigate the effects of supplemental but nontoxic amounts of orally administered magnesium ions on calcium and phosphate metabolism in adult male rats fed diets containing varied amounts of calcium and phosphorous. A 12 day balance period was investigated after the animals were habituated to their respective diets for 5 days.
GLP compliance:
Study predates GLP
Type of method:
in vivo
Endpoint addressed:
basic toxicokinetics

Test material

Constituent 1
Reference substance name:
Magnesium chloride hexahydrate (see endpoint summary for justification of read-across)
Magnesium chloride hexahydrate (see endpoint summary for justification of read-across)
Constituent 2
Reference substance name:
EC Number:
Cas Number:
Details on test material:

Test animals

other: Holtzman
Details on test animals or test system and environmental conditions:
- Weight at study initiation: 275 - 295 g
- Housing: During the balance period, each rat was kept in an individual stainless steel metabolism cage designed to separate urine from faeces.
- Diet (e.g. ad libitum): The basic diet contained 60% cerelose, 24% blood fibrin, 2% Alphacel, 10% Mazola oil, 4% salt mix and adequate amounts of all vitamins. All diets contained the same amounts of magnesium (0.05%) and trace elements. Each group of animals was fed a diet containing different percentages of calcium and phosphorous. Food intake was controlled so that the control rats and those supplemented with magnesium ate approximately the same amount during the balance period.
- Water (e.g. ad libitum): All animals received 40 mL of drinking solution and the magnesium supplemented rats usually drank between 30-40 mL daily while the controls drank it all.

Administration / exposure

Route of administration:
oral: drinking water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: MgCl2.6H2O was added to drinking water. To make the magnesiant solution more palatable and to ensure an adequate volume of urine, glucose to a final concentration of 10% (w/v) was added to the drinking water of all rats.
The control animals consumed approximately 50 mg of magnesium during the balance period i.e. 100 g food, while the magnesium supplemented rats consumed from 800 mg to 1000 mg.
Doses / concentrations
Doses / Concentrations:
2% MgCl2.6H2O (w/v)
nominal in water
No. of animals per sex per dose:
12 animals/ group, 12 groups in total
Control animals:
yes, concurrent vehicle
Details on study design:
After the 12 groups of rats were habituated to their respective diets for 5 days, each group of 12 rats was divided into 2 subgroups of 6 animals.


Urine and faeces were collected.
Calcium determinations were made by reverse flame photometry on urine directly and on faeces following ashing at 650 °C. Phosphorous was determined by a modification of the Fiske-SubbaRow procedure.

Results and discussion

Details on results:
Occasionally the rats supplemented with magnesium developed loose stools and diarrhoea for the first few days.

If the diets contained adequate amounts of calcium, supplemental magnesium decreased faecal calcium (increased absorption) and increased urinary calcium irrespective of the dietary level of calcium. The net effect of supplemental magnesium was to increase calcium balance. The mechanism for the increased absorption of calcium from the intestinal tract or the hypercalciuria is not known. Supplemental magnesium had no effect on phosphorous absorption when dietary phosphorous was suboptimal; it increased it when the dietary calcium to phosphorous ratio was low. The effects of magnesium on phosphate absorption appear to be the result of a magnesium-calcium interaction. Urinary phosphorous decreased with increasing magnesium intake. In general, magnesium increased phosphorous balance primarily as a result of renal conservation of phosphorous.

Applicant's summary and conclusion

There are significant interrelations between dietary phosphorous and magnesium as well as between calcium and magnesium in the absorption and homeostatic control of these substances..