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Toxicological information

Basic toxicokinetics

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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:
Study of magnesium bioavailability using stable isotopes and the inductively-coupled plasma mass spectrometry technique in the rat: single and double labelling approaches
Author:
Coudray, C.; et al.
Year:
1997
Bibliographic source:
Br. J. Nutr. 77: 957-970.

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Toxicokinetics, oral absorption (rat)
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Magnesium oxide
EC Number:
215-171-9
EC Name:
Magnesium oxide
IUPAC Name:
215-171-9
Constituent 2
Reference substance name:
1309-48-4
Cas Number:
1309-48-4
IUPAC Name:
1309-48-4
Constituent 3
Reference substance name:
magnesium oxide
IUPAC Name:
magnesium oxide
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): magnesium oxide
No further details are given.
Radiolabelling:
yes
Remarks:
enriched Mg isotopes (25Mg and 26Mg)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animals were derived from the colony of laboratory animals of the Institut National de la Recherche Agronomique, France.
- Age at study initiation: 7 weeks
- Weight at study initiation: 180g
- Diet: ad libitum (during acclimation period); semi-purified diet containing 1070 mg Mg/kg and distilled water
- Water: ad libitum (during acclimation period)
- Acclimation period: 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 45-50
- Photoperiod: 12 hours dark/light cycle
No further details are given.

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
water
Details on exposure:
Single labelling method: Stable isotope administration: The isotopic analysis of 25Mg as MgO yielded the following atom percent figures:
24Mg: 0.95%,
25Mg: 98.82%,
26Mg: 0.23%.
25Mg (100 mg) as oxide was moistened with distilled water and then HCl was added to transform the oxide into soluble chloride of Mg. The solution was diluted with water and the pH adjusted at 6 with powdered NaHCO3.

Double labelling method: table isotope administration: The isotopic analysis of 26Mg as MgO yielded the following atom percent figures:
24Mg: 0.41%
25Mg: 0.18%
26Mg: 99.41%.
26Mg (100 mg) as MgO was dissolved as indicated for 25Mg isotope. 1.5ml diluted 26Mg isotope solution (1 mg/mL) was mixed with 5g diet without Mg.
Duration and frequency of treatment / exposure:
Single labelling method: 1 administration
Double labelling method: 2 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
Single labelling method: On day 0 the animals in group 1 received 6 mg 25Mg and the animals in group 2 received 12 mg 25Mg by oral administration.
Double labelling method: On day 0 the animals received their diet containing 26Mg isotope (exact amount of 26Mg ingested was determined for each animal). Thereafter animals received 0.25 ml 25Mg (1.15 mg/ml) intravenously.
No. of animals per sex per dose / concentration:
Single labelling method: 10 rats were divided into two groups of 5 animals each.
Control animals:
not specified
Positive control reference chemical:
no data
Details on study design:
Single labelling method: Two successive 6 days balance periods were performed, one before and another after the administration of stable isotope. Daily Mg intake was determined and the faeces and urine of each rat were quantitatively collected.
Details on dosing and sampling:
Single labelling method: The faeces and urine of each rat for each day (before and for 6 days after isotope administration) were collected quantitatively. Animals were lightly anaesthetised and blood was sampled from the retro bulbar sinus before and at 0, 4, 8, 12 hours and 1, 3, and 6 days after stable isotope administration.

Double labelling method: Faeces and urine of each rat were collected before isotope administration (baseline) and then 12 hours collections were made quantitatively during the first 2 days and daily for the next 3 days after isotope administration. Animals were lightly anaesthetised and blood was sampled from the retro bulbar sinus before and at day 2 after stable-isotope administration.

Analysis: Urine volume was determined. Mg concentration and isotope ratios in plasma and urine were determined by ICP/MS. The Mg concentration and isotope ratios in faeces were determined by ICP/MS. Total Mg was determined by flame atomic absorption spectrometry.
Statistics:
Throughout the present study, results are expressed as mean and standard error (SE). The statistical significance of differences (P<0.05) was assessed using Student's t-test.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
True absorption of Mg in rats based on faecal elimination and total non-absorbed dose, and reported as 63-67% and 54-69% for doses of 33 and 66 mg/kg bw, respectively.
True absorption based on blood and urine data was calculated to 36-39%.
Details on distribution in tissues:
No data (not investigated).

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
Not relevant for magnesium.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Bioaccumulation is not relevant for magnesium.
True absorption of magnesium based on blood and urine data determined at 36-39 %.