Registration Dossier

Administrative data

Description of key information

Magnesium carbonate and Magnesium hydroxide are not consedered to be acutely harmful by oral route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1.7.2010-22.7.2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no
Specific details on test material used for the study:
- Description: white powder
- Batch No.: 078K0138
- Expiration date of the batch: 30 August 2013
- Storage condition of test material: room temperature in the dark
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 300 mg/kg dose group: 159 - 189 g; 2000 mg/kg dose group: 173 - 190 g
- Fasting period before study: Animals were fasted overnight prior to dosing
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: 2014 Teklad Global Rodent diet available ad libitum
- Water: mains drinking water available ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: For the purpose of the study the test material was freshly prepared, as required, as a suspension in distilled water.
The test material was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
5 animals/ group
Control animals:
no
Details on study design:
- The study procedure was as follows:
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose and a single animal was treated.
In the absence of mortality at a dose level of 300 mg/kg, an additional group of 4 animals was treated.
A total of five animals were therefore treated at a dose level of 300 mg/kg in the study.
In the absence of mortality at a dose level of 300 mg/kg, one additional animal was treated at a dose level of 2000 mg/kg.
In the absence of mortality at a dose level of 2000 mg/kg, an additional group of 4 animals was treated.
A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
Preliminary study:
At the 300 mg/kg dose level, there were no mortalities and ataxia and/or hunched posture were noted in all animals. However, animals appeared normal two or five days after dosing. All animals showed expected gains in bodyweight over the observation period and no abnormalities were noted at necropsy.
Based on the results at a dose level of 300 mg/kg, a dose level of 2000 mg/kg bodyweight was investigated.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks:
Magnesium Carbonate
Mortality:
At a dose level of 2000 mg/kg, there were no mortalities.
Clinical signs:
Hunched posture was noted in the initial treated animal during the day of dosing. No signs of systemic toxicity were noted in the additional four treated animals.
Body weight:
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.

Table 1: Individual Clinical Observations and Mortality Data - 300 mg/kg

Dose level

mg/kg

Animal number & sex

Effects noted after dosing

(hours)

Effects noted during period after dosing

(days)

0.5

1

2

4

1

2

3

4

5-14

300

1-0

Female

H

HA

HA

HA

HA

HA

H

H

0

2-0

Female

H

H

H

H

H

0

0

0

0

2-1

Female

0

H

HA

HA

H

0

0

0

0

2-2

Female

H

HA

HA

HA

H

0

0

0

0

2-3

Female

H

H

H

H

H

0

0

0

0

0 = No signs of systemic toxicity

H = hunched posture

A = ataxia

Table 2: Individual Bodyweights and Bodyweight Changes - 300 mg/kg

Dose level

mg/kg

Animal number & sex

Bodyweight (g) at Day

Bodyweight gain (g) during week

0

7

14

1

2

300

1-0

Female

159

163

181

4

18

2-0

Female

175

196

214

21

18

2-1

Female

171

190

199

19

9

2-2

Female

172

183

196

11

13

2-3

Female

189

202

217

13

15

Table 3: Individual Clinical Observations and Mortality Data - 2000 mg/kg

Dose level

mg/kg

Animal number & sex

Effects noted after dosing

(hours)

Effects noted during period after dosing

(days)

0.5

1

2

4

1-14

2000

3-0

Female

0

H

H

H

0

4-0

Female

0

0

0

0

0

4-1

Female

0

0

0

0

0

4-2

Female

0

0

0

0

0

4-3

Female

0

0

0

0

0

0 = No signs of systemic toxicity

H = hunched posture

  Table 4: Individual Bodyweights and Bodyweight Changes - 2000 mg/kg

Dose level

mg/kg

Animal number & sex

Bodyweight (g) at Day

Bodyweight gain (g) during week

0

7

14

1

2

300

3-0

Female

189

213

228

24

15

4-0

Female

190

207

214

17

7

4-1

Female

173

190

217

17

27

4-2

Female

178

196

216

18

20

4-3

Female

187

212

217

25

5

Interpretation of results:
GHS criteria not met
Remarks:
not classified
Conclusions:
The acute oral median lethal dose (LD50) of magnesium carbonate in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13.4.2010-29.4.2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to Guidelines in a GLP cerified laboratory
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
Identification: Magnesium hydroxide
Molecular formula: Mg(OH)2
Molecular weight: 58.32
CAS Number: 1309-42-8
Stable under storage conditions: Stable
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals 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
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred (see Table 1).
Clinical signs:
Hunched posture and/or piloerection was noted among all animals on Day 1 (see Table 2)
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untested animals of the same age and strain (see Table 3).
Other findings:
Macroscopic findings:
No abnormalities were found at macroscopic post mortem examination of the animals ( see Table 4).

Table 1: Mortality Rate

st 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:
The oral LD50 value of magnesium hydroxide in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 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:
- Globally Harmonised System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007)
-Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Executive summary:

First set of females- dose level = 2000 mg/kg

Second set of females- dose level= 2000 mg/kg

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute toxicity -oral route

The oral LD50 for magnesium carbonate when administered to rats was >2000 mg/kg bw.

Magnesium is also essential for life andoccurs in the natural environment. Humans are widely exposed to naturally occurring magnesium carbonate and chloride, e.g. via drinking water and food on a day to day basis. Ingested magnesium, carbonate and chloride ions are actively regulated by the body and are therefore not considered to be systemically toxic in standard test systems.

Justification for classification or non-classification

Oral:The oral LD50 for rats was > 2000 mg/kg bw in an OECD Guideline 420 study. Therefore the substance does not require classification according to the criteria described in Regulation (EC) No 1272/2008.