Magnesium

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: reasonably well-documented publication

Data source

Reference

Reference Type:

publication

Title:

Magnesium absorption from leafy vegetables intrinsically labeled with the stable isotope (26)Mg

Author:

Schwartz, R. et al.

Year:

1980

Bibliographic source:

J. Nutr. 110, 1365-1371

Materials and methods

Objective of study:

absorption

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

BToxicokinetics, rat
Oral bioavailability of dietary magnesium

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Magnesium chloride

EC Number:

232-094-6

EC Name:

Magnesium chloride

Cas Number:

7786-30-3

IUPAC Name:

magnesium dichloride

Test material form:

solid: compact

Details on test material:

- Name of test material (as cited in study report): 28 Mg as magnesium chloride

Radiolabelling:

yes

Remarks:

26Mg-labeled food, and 0.5 µCi 28MgCL2

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Wilmington, MA
- Weight at study initiation: 150-170 g
- Housing: The rats were housed in individual stainless steel cages.
- Diet: ad libitum
- Acclimation period: For 10 days before the test day the rats were trained to consume each evening an unlabeled test meal consisting of the vegetable in question, added to about 2 g powdered semi-synthetic laboratory diet made up without Mg and set in 0.3% agar.

ENVIRONMENTAL CONDITIONS
- Temperature: ambient temperature
- Photoperiod: 12 hours dark/light cycle

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on exposure:

On the test day the unlabeled food in each test meal was replaced by the corresponding 26Mg-labeled food. In addition, on that day, each test dish contained 0.5 µCi 28MgCl2, 0.1 µCi 14C-PEG and 0.02 g detergent-washed fibre prepared from the food to be tested and mordanted to chromium.
All doses contained approximately the same quantity of total Mg. Since the concentration of Mg in spinach 2 was approximately double the Mg concentration in the other vegetables, two types of spinach 2 doses were formulated. Spinach 2(a) contained the same amount of plant material as that contributed by the other vegetables, not supplemented by carrier Mg. Spinach 2(b) contained a smaller quantity of spinach that supplied about as much Mg as did the vegetables in all other test meals. The test food dishes were counted in a whole body counter before and after the dose had been consumed.
To allow for exact timing from consumption of the test meal to removal of tissues, the meals were presented consecutively to rats from each group at 8-minute intervals. One rat from each test group received the meal within the same hour to minimise the effect of time of food consumption on the rate of intestinal Mg absorption. As soon as the test meals were consumed, the rats were fitted with faecal collecting cups. Two hours later the rats were re-fed 5 g of the Mg-free powdered diet.

Duration and frequency of treatment / exposure:

see details on exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
Mg content by analysis: 21.89 ppm.
Mg content by analysis: 909.72 ppm

No. of animals per sex per dose / concentration:

Each food was tested in groups of eight rats of similar mean body weights.

Control animals:

not specified

Positive control reference chemical:

no data

Details on study design:

see attached file

Details on dosing and sampling:

12 hours after the test meals had been consumed, the rats were killed by heart puncture under ether anaesthesia. Blood was drawn into heparinised evacuated tubes and centrifuged for separation of plasma. Two millilitres plasma, the whole liver, stomach, small intestine and lower gastrointestinal tract (GIT) together with faeces were removed for measurement of radioactivity and for chemical analyses.

Statistics:

The data were analyzed by one-way analysis of variance followed, where appropriate, by Duncan's Multiple Range Test.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Mean values for true Mg absorption, estimated from measurement of radio activity remaining in the GIT, ranged from 45.4% of intake with turnip turnips to 49.7% for the spinach 2(b) test meal. Mean Mg absorption for the group consuming the standard test meal was 42.0%. The only statistically significant difference (P < 0.05 ) was that between the standard test meal and spinach 2(b). The mean ratio of 26Mg/28Mg was 0.99 ± 0.03 with a range of 0.96-1.05 for the vegetables. The 26Mg/28Mg ratio for the standard test meal was 0.97. Thus exchangeability of the two tracers was close
to 100%, with all meals tested.
On the average, about 85% of the PEG ingested had reached the lower GIT segments, compared to about 66% of Cr. Analysis of variance showed that overall transit time of either marker varied significantly with the nature of the test food. Although the rate of passage of the Cr-fibre marker was consistently lower than that of the soluble PEG marker, the nature of the test food affected the rates of passage of both markers similarly. Thus overall transit time was least for the group that had consumed the standard test meal and significantly greater for the groups testing collards and spinach 1. Percent residues of 28Mg in the stomach and intestine closely paralleled those of PEG, indicating that PEG is a valid marker for the soluble GIT phase containing the extrinsic Mg tracer.

Metabolite characterisation studies

Metabolites identified:

not specified

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Five leafy vegetables were grown in nutrient solutions in which the natural magnesium was replaced by the stable isotope, 26Mg. They were fed to rats in a test meal together with the extrinsic tracer 28Mg: a) to determine to what extent the instrinsic tracer (26Mg) was exchangeable with extrinsic 28Mg during the digestion and absorption processes, and b) measure the relative Mg availability from the different vegetables. The two tracers, 26Mg and 28Mg, were close to 100% exchangeable, as judged by the ratio of 26Mg/28Mg in the livers. Mean relative Mg absorption from the various vegetables ranged from 108 to 118% of the Mg absorbed from a standard test meal containing MgSO4. There were no statistically significant differences between the rates of Mg absorption from the five vegetables although two of the vegetables tested contained oxalate. The usefulness of stable 26Mg as a tracer in Mg bioavailability tests is discussed.

Executive summary:

Five leafy vegetables were grown in nutrient solutions in which the natural magnesium was replaced by the stable isotope, 26Mg. They were fed to rats in a test meal together with the extrinsic tracer 28Mg: a) to determine to what extent the instrinsic tracer (26Mg) was exchangeable with extrinsic 28Mg during the digestion and absorption processes, and b) measure the relative Mg availability from the different vegetables. The two tracers, 26Mg and 28Mg, were close to 100% exchangeable, as judged by the ratio of 26Mg/28Mg in the livers. Mean relative Mg absorption from the various vegetables ranged from 108 to 118% of the Mg absorbed from a standard test meal containing MgSO4. There were no statistically significant differences between the rates of Mg absorption from the five vegetables although two of the vegetables tested contained oxalate. The usefulness of stable 26Mg as a tracer in Mg bioavailability tests is discussed.