Magnesium

Immunotoxicity

Description of key information

There are conclusive but not suffcient data for the classification of substance Magnesium (CAS No. 7439-95-4) with regard to Immunotoxicity.

Key value for chemical safety assessment

Effect on immunotoxicity: via oral route

Link to relevant study records

Reference

Endpoint:

immunotoxicity: short-term oral

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 documented study which meets basic scientific principles

Qualifier:

no guideline followed

Principles of method if other than guideline:

The effects of gestational Mg or Zn deficiency on the humoral or cellular immunity of newborn rats were investigated. Mg deficiency was induced by feeding a diet containing 180 ppm Mg from day 0 to day 21 of gestation and Zn deficiency was induced by feeding a diet containing 1.5 ppm Zn from day 0 to day 19. Controls were fed a diet with 1,000 ppm Mg and 100 ppm Zn from day 0 to day 21.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

oral: feed

Vehicle:

water

Details on exposure:

The effects of gestational Mg or Zn deficiency on the humoral or cellular immunity of newborn rats were investigated.
Mg deficiency was induced by feeding a diet containing 180 ppm Mg from day 0 to day 21 of gestation and Zn deficiency was induced by feeding a diet containing 1.5 ppm Zn from day 0 to day 19.
Controls were fed a diet with 1,000 ppm Mg and 100 ppm Zn from day 0 to day 21.
Thereafter, all maternal rats and newborns were fed diets with normal amounts of Mg or Zn.
Three and six weeks after birth, T-cell subpopulations in blood and thymus and B-cells in blood of the newborns were detected by flow cytometry.
Plasma contents of IgG, IgM, and IgA were determined by radial immunodiffusion. Mg deficiency reduced litter size and pup weight.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

21 days

Frequency of treatment:

daily

Control animals:

yes

Observations and clinical examinations performed and frequency:

T-cell subpopulations in blood and thymus and B-cells in blood of the newborns were detected by flow cytometry. Plasma contents of IgG, IgM, and IgA were determined by radial immunodiffusion.

Sacrifice and pathology:

GROSS PATHOLOGY AND HISTOPATHOLOGY: Yes. T-cell subpopulations in blood and thymus and B-cells in blood of the newborns were detected by flow cytometry. Plasma contents of IgG, IgM, and IgA were determined by radial immunodiffusion.

Humoral immunity examinations:

The effects of gestational Mg or Zn deficiency on the humoral or cellular immunity of newborn rats were investigated. Mg deficiency was induced by feeding a diet containing 180 ppm Mg from day 0 to day 21 of gestation and Zn deficiency was induced by feeding a diet containing 1.5 ppm Zn from day 0 to day 19.
Controls were fed a diet with 1,000 ppm Mg and 100 ppm Zn from day 0 to day 21.
Thereafter, all maternal rats and newborns were fed diets with normal amounts of Mg or Zn.
Three and six weeks after birth, T-cell subpopulations in blood and thymus and B-cells in blood of the newborns were detected by flow cytometry.
Plasma contents of IgG, IgM, and IgA were determined by radial immunodiffusion.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Details on results:

No effects on T-cell subpopulations in isolated thymocytes were detected after gestational Mg.
Three and six weeks after birth, body weight, number of leukocytes, lymphocyte, and T-cell subpopulations were not significantly changed.

Cell viabilities:

effects observed, treatment-related

Humoral immunity examinations:

effects observed, treatment-related

Dose descriptor:

NOAEL

Effect level:

3 780 mg/kg bw/day (actual dose received)

Based on:

dissolved

Remarks:

Magnesium

Sex:

male/female

Basis for effect level:

other: No effects on T-cell subpopulations in isolated thymocytes were detected after gestational Mg. Three and six weeks after birth, body weight, number of leukocytes, lymphocyte, and T-cell subpopulations were not significantly changed.

Conclusions:

No effects on T-cell subpopulations in isolated thymocytes were detected after gestational Mg.
Three and six weeks after birth, body weight, number of leukocytes, lymphocyte, and T-cell subpopulations were not significantly changed.

Executive summary:

The effects of gestational Mg or Zn deficiency on the humoral or cellular immunity of newborn rats were investigated. Mg deficiency was induced by feeding a diet containing 180 ppm Mg from day 0 to day 21 of gestation and Zn deficiency was induced by feeding a diet containing 1.5 ppm Zn from day 0 to day 19. Controls were fed a diet with 1,000 ppm Mg and 100 ppm Zn from day 0 to day 21. Thereafter, all maternal rats and newborns were fed diets with normal amounts of Mg or Zn. Three and six weeks after birth, T-cell subpopulations in blood and thymus and B-cells in blood of the newborns were detected by flow cytometry. Plasma contents of IgG, IgM, and IgA were determined by radial immunodiffusion. Mg deficiency reduced litter size and pup weight. Three weeks after birth, the total number of leukocytes and lymphocytes in blood was significantly decreased, due to a reduction of T-helper and cytotoxic T-cells. Activated T-cells and B-cells were unchanged. Six weeks after birth, T-cell subpopulations approached controls values, whereas IgG content in plasma was slightly reduced. Gestational Zn deficiency reduced litter size and induced malformations. Three and six weeks after birth, body weight, number of leukocytes, lymphocyte, and T-cell subpopulations were not significantly changed. Plasma IgM was decreased 3 weeks after birth in correlation to the number of B-cells, which represented only 4% of total lymphocytes. These effects were repaired by the sixth week. Plasma IgG was reduced at 6 weeks. No effects on T-cell subpopulations in isolated thymocytes were detected after gestational Mg or Zn deficiency.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

3 780 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Effect on immunotoxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

164.3 mg/m³

Study duration:

subchronic

Species:

rat

Effect on immunotoxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

94.5 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

Oral exposure:

No effects on T-cell subpopulations in isolated thymocytes were detected after gestational Mg.

Three and six weeks after birth, body weight, number of leukocytes, lymphocyte, and T-cell subpopulations were not significantly changed. NOAEL=3780 mg/kg bw/day

 

Dermal exposure:

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

 corrected dermal NOAEL=   oral NOAEL

3780 mg/kg bw/dayx0.025 kg =                  

 NOAELrat  = 94.5 mg/kg bw/day

 

Inhalation exposure:

The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m³), assuming 100 % absorption for both routes.

NOAEL rat      =  3780 mg/kg bw/day

÷1.15 m3/kgbw

÷20m3/rat

NOAECrat  = 164.3 mg/m3

Justification for selection of effect on immunotoxicity via inhalation route endpoint:
Inhalation exposure:
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat      =  3780 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat  = 164.3 mg/m3

Justification for selection of effect on immunotoxicity via dermal route endpoint:
Dermal exposure:
For dermal exposure we taken that:
-the average weight of rats is 250g (200-300g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg
 corrected dermal NOAEL=   oral NOAEL
3780 mg/kg bw/dayx0.025 kg =                  
 NOAELrat  = 94.5 mg/kg bw/day

Justification for classification or non-classification

There are conclusive but not suffcient data for the classification of substance Magnesium (CAS No. 7439 -95 -4) with regard to Immunotoxicity.