Magnesium

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

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: Well documented study which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Modulation of peripheral lymphocyte and alveolar macrophage activity by magnesite emissions

Author:

Reichrtova E, et al

Year:

1982

Bibliographic source:

J Hyg Epidemiol Microbiol Immunol 26 (4): 367-374 (1982)

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Deviations:

not specified

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Magnesium oxide

EC Number:

215-171-9

EC Name:

Magnesium oxide

Cas Number:

1309-48-4

IUPAC Name:

magnesium oxide

Test material form:

aerosol dispenser: not specified

Remarks:

migrated information: aerosol

Details on test material:

magnesite composition: MgO 88.52%, Fe2O3 7.57%, CaO 2.74%, Al2O3 0.49%, SiO2 0.68%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: The MMAD (mass median aerodynamic diameter) of the aerosols was 1.8 μm. (mean dust particle diameter of 1.8 μm).

Details on inhalation exposure:

In experimental exposure chambers, aerosols were prepared using particulates that were collected from electrostatic filters in a Slovak magnesite
work, consisting of 88.5% MgO, 7.6% Fe2O3, 2.7% CaO, 0.5% Al2O3, SiO2, and traces of other elements and having a mean dust particle diameter of
1.8 μm.
Wistar rats and C57 BL mice were exposed to concentrations ranging from 10- 1000 mg/m3, 3-5 hours/day, 5 days/week, for 3-9 months.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

70 days for rats

Frequency of treatment:

4 hours/day, 5 days/week, for 70 days for rats

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
10 mg/m3
Basis:
analytical conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
50 mg/m3
Basis:
analytical conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
10- 1000 mg/m3
Basis:
analytical conc.

Control animals:

not specified

Details on study design:

In experimental exposure chambers, aerosols were prepared using particulates that were collected from electrostatic filters in a Slovak magnesite
work, consisting of 88.5% MgO, 7.6% Fe2O3, 2.7% CaO, 0.5% Al2O3, SiO2, and traces of other elements and having a mean dust particle diameter of 1.8 μm. Wistar rats and C57 BL mice were exposed to concentrations ranging from 10- 1000 mg/m3, 3-5 hours/day, 5 days/week, for 3-9 months

Positive control:

no

Examinations

Observations and examinations performed and frequency:

Reichrtová et al. studied the effects of exposure to magnesite ‘dusts’ in rats, in laboratory as well as in field conditions in which animals housed in stations built on a distance from magnesite works were exposed to magnesite-work emissions (‘dust fallout’).
In experimental exposure chambers, aerosols were prepared using particulates that were collected from electrostatic filters in a Slovak magnesite
work, consisting of 88.5% MgO, 7.6% Fe2O3, 2.7% CaO, 0.5% Al2O3, SiO2, and traces of other elements and having a mean dust particle diameter of 1.8 μm. Wistar rats and C57 BL mice were exposed to concentrations ranging from 10- 1000 mg/m3, 3-5 hours/day, 5 days/week, for 3-9 months.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

no effects observed

Details on results:

Exposure to magnesium-polluted ambient air was found to increase the number of alveolar macrophages, to stimulate acid phosphatase activity in these cells, and to enhance activity of peripheral B lymphocytes to form EAC rosettes.
The inhalation chamber experiments, evaluated after 46 and 70 days of exposure, resulted in an enhanced acid phosphatase activity of alveolar macrophages, enhanced lactate dehydrogenase activity of peripheral lymphocytes and in an increased percentage of B lymphocytes in blood, depending on exposure time. This activation clearly suggest that the cells participating in the induction and expression of the immune response are distinctly modulated in their activity by in vivo exposure to magnesite dust.

Effect levels

Dose descriptor:

LOAEC

Effect level:

50 mg/m³ air (analytical)

Based on:

dissolved

Sex:

female

Basis for effect level:

other: statistically significant increases in the number of B lymphocytes in blood, in lactate dehydrogenase activity in lymphocytes, and in the acid phosphatase activity in alveolar macrophages were found at the end of the exposure period.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Histological examination of the organs showed a marked stimulation of the reticuloendothelial cells in the lungs and spleen. The overall lung tissue structure retained its normal appearance, except for a slight hypertrophy of interalveolar septa. Some alveoli were packed with macrophages. The histological changes in the spleen were characterised by growth of malphigian corpuscles and migration of lymphocytes into the spleen red pulp. The reticulin stroma of the spleen was unaltered. No histological changes were observed in liver and kidneys. Reichrtová et al. concluded that subchronic exposure to these dusts might modulate the activity of cells participating in the induction and expression of immune response.

Applicant's summary and conclusion

Conclusions:

In rats exposed to dust aerosols of 50 mg/m3, 4 hours/day, 5 days/week, for 70 days, the LOAEC was established at 50 mg/m3, based on effects statistically significant increases in the number of B lymphocytes in blood, in lactate dehydrogenase activity in lymphocytes, and in the acid phosphatase activity in alveolar macrophages were found at the end of the exposure period.

Executive summary:

In rats exposed to dust aerosols of 50 mg/m3, 4 hours/day, 5 days/week, for70 days, statistically significant increases in the number of B lymphocytes in blood, in lactate dehydrogenase activity in lymphocytes, and in the acidphosphatase activity in alveolar macrophages were found at the end of theexposure period. Histological examination of the organs showed a markedstimulation of the reticuloendothelial cells in the lungs and spleen. The overalllung tissue structure retained its normal appearance, except for a slighthypertrophy of interalveolar septa. Some alveoli were packed with macrophages.The histological changes in the spleen were characterised by growth ofmalphigian corpuscles and migration of lymphocytes into the spleen red pulp.The reticulin stroma of the spleen was unaltered. No histological changes wereobserved in liver and kidneys. Reichrtová et al. concluded that subchronicexposure to these dusts might modulate the activity of cells participating in theinduction and expression of immune response.