Magnesium

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:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well conducted study, meets general scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Urinary and Fecal Excretion of Orally Administered Mg28

Author:

Aikawa JK, Rhoades EL & Gordon GS

Year:

1958

Bibliographic source:

Proc. Soc. Exp. Biol. Med., 98(1): 29-31

Materials and methods

Type of study / information:

behaviour of orally administered magnesium, using Mg28 as tracer. Urinary and faecal excretion of the isotope was measured.

Endpoint addressed:

basic toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The purpose of the study was to follow the behaviour of orally administered magnesium, using Mg28 as tracer. Urinary and faecal excretion of the isotope was measured.

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:

Radioactive magnesium (Mg28) as magnesium chloride

Method

Ethical approval:

not specified

Details on study design:

Initial observations (Group A) were made in 12 hospitalised adult male convalescents from various diseases. None had any symptoms or signs of gastrointestinal disturbances and all were on regular hospital diet.

Exposure assessment:

measured

Details on exposure:

Radioactive magnesium (Mg28) as magnesium chloride in an acid solution, was given in water, usually mid-morning. The doses of 10 to 25 µC was contained in 3 to 10 meq of magnesium.
All urine passed within the next 24 hours was collected in chemically clean glassware.
7 patients were given one dose of Mg28; 4 were given 2 doses a week apart and the 12th patient given 3 doses of tracer at weekly intervals.
Subsequent studies (Groups B, C and D) were done in 14 healthy medical students. Each student received orally 10 µC of Mg28 contained in 3 meq of magnesium. In 7 instances (Groups C and D), 2 gelatin capsules containing a gram of carmine were given at the same time. In addition to specimens of urine and faeces collected in chemically clean glassware from all students, several venous blood specimens were obtained from 3 students in Group D. 2 students (#11 and 12) were given a second dose of isotope one week after the first.
Radioactivity of urine, plasma and faeces was determined with a well-type scintillation counter and a scaling circuit. Stool specimens were digested in concentration sulfuric acid and nitric acids prior to radioactivity assay. A total of 10,000 counts were made on each sample. All determinations were corrected for physical decay of isotope.

Results and discussion

Results:

The maximum 24 hour urinary excretion rate for Mg28 in hospitalised patients (Group A) was 6.27%; the mean was 2.11 ± 1.61%. Except in one patient, the second and third determinations of urinary excretion rate gave results closely comparable to the first.
The 24 hour urinary excretion of radioactivity in the first 9 medical students (Group B) was between 1.13 and 4.93% of total administered dose, mean value being 2.88 ± 1.27%. Maximum total radioactivity recovered in stools within the first 48 hours was 61.85%.
Four other students (Group C) were then given, in addition to the same dose of Mg28, the carmine indicator. Stools were collected for 96 hours or until the red colour had disappeared. Urine specimens were collected for 48 hours. Urinary excretion of radioactivity during the first 24 hours was comparable to that observed in Groups A and B; excretion of Mg28 during the second 24-hour period was consistently lower than that during the first 24 hours. Maximum faecal recovery rate obtained in this group was 85.16%. Radioactivity was usually greatest in stools with most intense red colour.
In the final set of observations (Group D), 3 students were given the same tracer dose of Mg28 and the carmine dye but urine collections were extended over 72 hours and faecal collections through 120 hours. Urinary excretion of Mg28 during the first 48 hours was comparable to that observed in Group C; amount of Mg28 excreted during 48-72 hour period was lower than that observed in either of the preceding 24 hour periods. Maximum % of radioactivity recovered in stools was 87.97%. In one subject, 96% of radioactivity was recovered in stool and urine.
Blood specimens were obtained at 2,4,6 and 8 hours after oral administration of Mg28 to 3 students in Group D. Calculations based on specific activity of material administered showed that rise in serum magnesium concentration attributable to orally administered material was in the order of 0.75 to 3.85 x 10-5 meq/L; the highest concentration in each subject was found at 4 hours.

Any other information on results incl. tables

Table 1: Urinary and faecal excretion of Mg28 following oral administration

Patient No.	% of dose recovered in urine				% of dose recovered in stool
	0-24 h	24-48 h	48-72 h	Total	0-24 h	24-48 h	48-72 h	72-96 h	96-120 h	Total
Medical students
Group C
10	2.87	1.77	-	-	60.13	14.48	0.65	-	-	75.26
11-1	4.27	2.72	-	-	0.10	7.16	35.26	42.64	-	85.16
12-1	2.17	1.55	-	-	24.34	26.46	-	24.45	-	75.25
13	1.71	1.14	-	-	0	45.66	4.11	6.56	-	56.33
Mean	2.76	2.39	-	-	-	-	-	-	-
Group D
11-2	3.18	2.02	1.05	6.25	0.22	1.56	11.67	32.26	37.08	82.79
12-2	3.98	3.28	0.91	8.17	1.14	25.30	-	-	61.53	87.97
14	1.24	1.80	0.17	3.21	41.62	14.28	3.50	-	-	59.40
Mean	2.80	2.37	0.71	-	-	-	-	-	-	-

Table 2: Plasma radioactivity concentration following oral administration of Mg28

Subject	Hours after oral ingestion
	2	4	6	8
11-2	1.05*	3.85	3.46	2.73
12-2	1.10	2.26	1.96	1.07
14	0.75	1.12	1.09	-

* all values = x 10^-5meq/L and are based on specific activity of the material administered

 

Applicant's summary and conclusion

Conclusions:

Urinary excretion within 72 hours accounted for less than 10% of the total dose of Mg28; the maximal excretion (6.3%) occurred during the first 24 hour period. Maximal concentration of radioactivity in plasma occurred at 4 hours but the actual increase in serum magnesium was negligible. Faecal excretion within 120 hours accounted for 60 to 88% of administered dose. Low renal excretion of magnesium is believed to be due to poor gastrointestinal absorption of this material.