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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-04-13 to 2010-04-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to Guidelines in a GLP certified laboratory.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
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
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
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
Details on test material:
Identification: Magnesium hydroxide
Molecular formula: Mg(OH)2
Molecular weight: 58.32
CAS Number: 1309-42-8
Stable under storage conditions: Stable

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels
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).

Any other information on results incl. tables

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

 

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
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.