Magnesium hydroxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-09-01 to 2010-10-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Magnesium hydroxide

EC Number:

215-170-3

EC Name:

Magnesium hydroxide

Cas Number:

1309-42-8

Molecular formula:

H2MgO2

IUPAC Name:

magnesium dihydroxide

Specific details on test material used for the study:

- Name of the test material used in the report: Magnesium hydroxide
- Appearance: white powder
- Batch No.: 20BR0026
- Purity: 99.90%
- Storage: at room temperature in the dark
- Expiry date: 2012-01-31

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species
Rat: Crl:WI(Han) (outbred, SPF-Quality)
Recognised by international guidelines as the recommended test system (e.g. OECD, EC).
Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals
5 males and 5 females (females were nulliparous and non-pregnant) per exposure level.
Age and body weight
Young adult animals were selected (approximately \ weeks old).
Animals used within the study were of approximately the same age and body weight variation did not exceed +/- 20% of the sex mean.
Identification
Earmark
Health inspection
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

3.3 µm

Geometric standard deviation (GSD):

1.7

Details on inhalation exposure:

Test atmosphere generation
Administering the test substance to a stream of dry pressurized air using a combination of a spiral feeder and air mover generated an aerosol. The aerosol was passed through a cyclone, allowing larger particles to settle, before it entered the exposure chamber (Appendix 1, Figure 1). The mean total airflow was 47 L/min. From the exposure chamber the test atmosphere was passed through a filter before it was released to the exhaust of the fume hood.

Nominal concentration
The nominal concentration was calculated by dividing the amount of test substance used by the volume of pressurized air (average air flow times exposure time) entering the exposure chamber used for exposure of the animals.

Actual concentration
The actual concentration was determined twelve times during the exposure period. Samples were drawn from the test atmosphere through a tube mounted in one of the free animal ports of the middle section of the exposure chamber. Samples were drawn through a glass fiber filter (type APFC04700, Millipore, Billerica, MA, USA). The collected amount of the test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter (type G 1.6, Actaris Meterfabriek B.V., Dordrecht, The Netherlands).

Subsequently the mean concentration with the standard deviation was calculated.

The particle size distribution was characterized twice during the exposure period. The samples were drawn (2 L/min) from the test atmosphere through a tube mounted in one of the free animal ports of the middle section of the exposure chamber (Appendix 1, Figures 1 and 2). The samples were collected with an 8 stage Marple personal cascade impactor containing fiber glass filters (SKC 225-713, fiber glass, SKC Omega Specialty Division, Chelmsford, MA, USA) and a fiber glass back-up filter (SEC-290-GFS, Westech, Upper Stondon, Bedfordshire, England). Amounts of test substance collected were measured gravimetrically. Subsequently the Mass Median Aerodynamic Diameter (MMAD) and the Geometric Standard Deviation (GSD) were determined.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The collected amount of the test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter (type G 1.6, Actaris Meterfabriek B.V., Dordrecht, The Netherlands).

Duration of exposure:

4 h

Concentrations:

The mean actual concentration was 2.1 ± 0.47 mg/L. The nominal concentration was 21.7 mg/L resulting in a generation efficiency (ratio of actual and nominal concentration) of 10%. The concentration measurements distributed over time showed that the substance was sufficiently stable

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Days 1 (pre-administration), 2, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: On Day 1, one and three hours after exposure and once daily thereafter until Day 15.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.1 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were noted during exposure. After exposure, ptosis and/or piloerection were noted in two males and one female on Day 1 only.

Body weight:

Overall body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The inhalatory LC50 of Magnesium hydroxide in Wistar rats was established to exceed 2.1 mg/L.

Executive summary:

In an acute inhalation toxicity study conducted according to OECD 403, groups of 5 male and female Wistar rats were treated with Magnesium hydroxide (99.9% purity) as aerosol during 4 hours. No mortality or other relevant adverse effects were observed. No clinical signs were noted during exposure. After exposure, ptosis and/or piloerection were noted in two males and one female on Day 1 only.

Overall body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals.

An inhalatory LC50 (4 h) value for magnesium hydroxide exceeding 2.1 mg/L was determined, being this value the maximum feasible concentration that could be tested.