Magnesium hydroxide

Endpoint summary

Description of key information

In an acute oral toxicity study in rats conducted according to OECD 423, no mortality occurred at the dose level 2000 mg/kg bw. Hence, the LD50 was determined to exceed 2000 mg/kg body weight.

 In an acute inhalation toxicity study conducted according to OECD 403, the inhalatory LC50 of Magnesium hydroxide in Wistar rats was established to exceed 2.1 mg/L, being this value the maximum feasible concentration that could be tested.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-04-13 to 2010-06-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

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

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 8 weeks approx.
- Weight at study initiation: Body weight variation of selected animals did not exceed +/- 20% of the sex mean
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages containing sterilised sawdust as bedding material
- Diet: Pelleted rodent diet was available ad libitum
- Water: Ad libitum
- Acclimation period: Not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 - 21.5 °C
- Humidity (%): 34 - 60 %
- Photoperiod (hrs dark / hrs light): 12 hours dark and 12 hours light

IN-LIFE DATES: From: 13th April 2010 To: 29th April 2010

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Standard vehicle for use in testing


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Limit test

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 female animals per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortaility/viability twice daily. Body weights were measured on day 1 (pre-administration), day 8 and day 15.
- Necropsy of survivors performed: Yes.
- Other examinations performed: Clinical signs were observed at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.

Statistics:

Not required

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred (see Table 1).

Clinical signs:

other: Hunched posture and/or piloerection was noted among all animals on Day 1 (see Table 2).

Other findings:

Macroscopic findings:
No abnormalities were found at macroscopic post mortem examination of the animals ( see Table 4).

Table 1: Mortality Rate

Test day

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Hours after treatment

0

2

4

Females 2000 MG/KG

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Females 2000 MG/KG

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

 Key: X= no signs observed

 Table 2: Clinical Signs

Test day

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Hours after treatment

Max grade

0

2

4

Females 2000MG/KG Animal 1

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Skin/fur Piloerection

(1)

X

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Animal 2

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Animal 3

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Females 2000 MG/KG  Aniaml 4

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Skin/fur piloerection

(1)

X

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Animal 5

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Skin/fur piloerection

(1)

X

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Animal 6

Posture Hunched posture

(1)

√

√

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Skin/fur piloerection

(1)

X

√

X

X

X

X

X

X

X

X

X

X

X

X

X

X

X

Key: X= no signs observed

√=signs observed

Table 3: Body Weights (Gram)

Sex/Dose	Animal	Day 1	Day 8	Day 15
Females 2000 MG/KG
	1	149	175	189
	2	151	180	192
	3	146	174	189
	Mean	149	176	190
	St. Dev	3	3	2
	N	3	3	3
	4	155	179	196
	5	153	174	188
	6	161	185	194
	Mean	156	179	193
	St.Dev	4	6	4
	N	3	3	3

 

Table 4: Macroscopic Findings

Animal Organ	Finding	Day of Death
Females 2000 Mg/Kg
1	No Findings Noted	Scheduled necropsy Day 15 after treatment
2	No Findings Noted	Scheduled necropsy Day 15 after treatment
3	No Findings Noted	Scheduled necropsy Day 15 after treatment
Females 2000 Mg/Kg
4	No Findings Noted	Scheduled necropsy Day 15 after treatment
5	No Findings Noted	Scheduled necropsy Day 15 after treatment
6	No Findings Noted	Scheduled necropsy Day 15 after treatment

 

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study in rats conducted according to OECD 423, no mortality occurred at the dose level 2000 mg/kg bw. Hence, the LD50 was determined to exceed 2000 mg/kg body weight.

Executive summary:

In an acute oral toxicity study conducted according to OECD 423, groups of female Wistar rats (3 per group) were given a single dose of magnesium hydroxide (purity 99.9%) diluted in water at a dose of 2000 mg/kg bw. Animals were observed for 14 days.

No mortality occurred. Hunched posture and/or piloerection was noted among all animals on Day 1. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals.

Based on the results from this study, the oral LD50 value in rats is considered to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

GLP guideline study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

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

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.

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 2.1 mg/L air

Physical form:

inhalation: aerosol

Quality of whole database:

GLP guideline study

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

According to the key study, the oral LD50 value of Magnesium hydroxide in Wister rats was established to exceed 2000 mg/kg body weight. Based on these results, Magnesium hydroxide does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the CLP regulation 1272/2008.

Furthermore, Magnesium hydroxide is used extensively as a medical drug in humans as an antacid to neutralise stomach acid and assist in the treatment of indigestion and heartburn. It is also used as a laxative and as an antiperspirant deodorant and can be useful as a topical treatment for canker sores. In its form as an indigestion and heartburn treatment, it is sold over the counter in most supermarkets, chemists and convenience stores and does not require a prescription from a physician to be purchased. It is administered orally, usually as a chewable tablet, capsule or a suspension in water known as milk of magnesia.

The ubiquitous use of magnesium hydroxide under these therapeutic conditions, with direct skin and oral exposure, further contributes to the evidence that magnesium hydroxide is a substance of low toxicological concern.

According to the key study, the inhalatory LC50 (4h) value of Magnesium hydroxide in Wistar rats exceeded 2.1 mg/L, which was the technical maximum feasible concentration that could be tested.

Furthermore, according to Annex VIII of Regulation (EC) No 1907/2006, a study on acute dermal toxicity is not required if oral and inhalation acute toxicity studies are provided. As there are studies to address oral and inhalation toxicity, a test on dermal toxicity is not scientifically justified. Furthermore it is unlikely that dermal absorption of an ionic compound will exceed the oral absorption. As the acute oral toxicity was low (LD50 > 2000 mg/kg bw in rats) this can reasonably be expected to be the case for acute dermal toxicity as well.

Based on these results, Magnesium hydroxide does not have to be classified and has no obligatory labelling requirement for acute inhalation toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) and CLP Regulation (EC) No 1272/2008.

Justification for classification or non-classification

Based on the results, Magnesium hydroxide does not have to be classified and has no obligatory labelling requirement for acute inhalation, dermal or oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) and the CLP Regulation (EC) No 1272/2008.