Magnesium

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: gene mutation

Remarks:

Type of genotoxicity: gene mutation

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: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Effect of magnesium sulphate on adriamycin-induced calstogenic and biochemical changes in Swiss Albino Mice

Author:

Al-Shabanah OA

Year:

1998

Bibliographic source:

Chemotherapy 44: 272-283

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The micronucleus test procedure described by Schmid was used (Schmid W, 1975, The micronucleus test. Mutation
Research 31: 9-15.).

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Magnesium sulphate

IUPAC Name:

Magnesium sulphate

Constituent 2

Reference substance name:

Magnesium sulphate

EC Number:

231-298-2

EC Name:

Magnesium sulphate

Cas Number:

7487-88-9

IUPAC Name:

7487-88-9

Test material form:

solid: compact

Details on test material:

- Molecular formation: MgSO4
- Supplier: BDH Limited, Poole, UK
- Lot No.: Not reported
- Purity: Not reported
- Storage condition: Not reported

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Experimental Animal Car Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia)
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: 25 to 30 grams
- Assigned to test groups randomly: yes
- Fasting period before study: Not reported
- Housing: Not reported
- Diet (e.g. ad libitum): ad libitum (Purina chow diet)
- Water (e.g. ad libitum): ad libitum (Not reported to water source)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 to 25 °C
- Humidity (%): 40 to 50 %
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

The doses selected (125–500 mg/kg body weight) were based on the anticlastogenic activity of the highest dose (500 mg/kg body weight) of magnesium sulfate observed in a preliminary study. The different experimental groups of mice consisted of: (1) untreated control (distilled water); (2) magnesium sulphate, 125 mg/kg/day; (3) magnesium sulphate, 250 mg/kg/day; (4) magnesium sulphate, 500 mg/kg/day. Magnesium sulphate was dissolved in water and administered by gavage to mice in groups 2, 3 and 4 for 7 days.

Duration of treatment / exposure:

Magnesium sulfate was administered by gavage to mice for 7 days.

Frequency of treatment:

once a day

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 125, 250 and 500 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

5 mice/male/dose

Control animals:

yes, concurrent vehicle

Examinations

Tissues and cell types examined:

The micronucleus test used to determine the clastogenicity in femoral marrow cells.

Details of tissue and slide preparation:

Freshly killed animals, both the femoral were removed in toto and freed from muscles. The femoral marrow cells were aspirated in fetal calf serum as a find suspension and centrifuged. After centrifugation, the cells were spread on slides and air dried. Coded slides were fixed in methanol and stained with Ma-Gruenwald solution followed by Giemsa staining.

Evaluation criteria:

Polychromatic erythrocytes (PCE) were screened for micronuclei, and normochromatic erythrocytes (NCE) were recorded. The PCE/NCE ratio was calculated to analyse the bone marrow depression.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Any other information on results incl. tables

Table 1. Effect of magnesium sulfate on micronuclei in mice

Dose (mg/kg bw)	Duration of treatment	PCE Screence	Mean micronucleated PCE+/-SE, %	NCE Screened	Mean PCE/NCE ratio+/-SE
0	12	5,127	0.29 +/-0.03	4,917	1.04 +/-0.03
	24	5,120	0.27 +/-0.03	5,021	1.02 +/-0.03
	48	5,064	0.27 +/-0.04	5,049	1.00 +/-0.01
125	12	5,175	0.41 +/-0.05	5,256	0.99 +/-0.04
	24	5,190	0.28 +/-0.02	5,129	1.01 +/-0.02
	48	5,090	0.31 +/-0.04	5,143	0.99 +/-0.02
250	12	5,239	0.32 +/-0.05	5,401	0.97 +/-0.04
	24	5,260	0.30 +/-0.02	5,180	1.02 +/-0.04
	48	5,242	0.28 +/-0.03	5,346	0.99 +/-0.04
500	12	5,483	0.33 +/-0.04	5,429	1.01 +/-0.03
	24	5,300	0.30 +/-0.03	5,280	1.00 +/-0.03
	48	5,242	0.29 +/-0.03	5,260	1.00 +/-0.05

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Based on the results, the treatment with magnesium sulfate did not induce any significant changes in the frequency of micronuclei in PCE and the PCE/NCE ratio at different doses and durations of treatment as compared to control.