Magnesium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 2009 till december 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

magnesium chloride hexahydrate

IUPAC Name:

magnesium chloride hexahydrate

Constituent 2

Reference substance name:

7791-18-6

Cas Number:

7791-18-6

IUPAC Name:

7791-18-6

Details on test material:

water content (specification): 51-55 % (53.4 %)
Colour: colourless
Physical state: solid, crystals
Storage: at room temperature, in a tightly closed package
Solvent: water
Stability after opening: instable after repeated contact to air
pH: 5.5 - 7.0 (5 % solution at 20 °C)

Specific details on test material used for the study:

- Name of test material (as cited in study report): Magnesium chloride hexahydrate
- EC-Number: 232-094-6
- Physical state: Colourless; Solid, crystals
- Stability after opening: Instable after repeated contact to air
- Storage condition of test material: At room temperature, in a tightly closed package.
- pH: 5.5 - 7.0 (5% solution at 20 °C)
- Solvent: Water
No further information on the test material was stated.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species/strain: Healthy rats, WISTAR rats Crl: WI(Han) (Full-Barrier)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: female, non-pregnant, nulliparous
Age at the beginning of the study: 8 - 12 weeks old
Body weight at the beginning of the study: animals no. 1 – 3, step 1: 151 – 158 g and animals no. 4 – 6, step 2: 161 – 170 g;
The animals were derived from a controlled full barrier maintained breeding system (SPF).

Housing and Feeding Conditions: full-barrier in an air-conditioned room, temperature: 22 (+/-3) °C, relative humidity: 55 (+/-10) %, artificial light, sequence being 12 hours light, 12 hours dark, air change: 10 x / hour, free access to Altromin 1324 maintenance diet, free access to tap water, sulphur acidified to a pH value of approx. 2.8, the animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding, adequate acclimatisation period (at least five days).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Aqua ad injectionem

Details on oral exposure:

The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 5 mL/kg body weight.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 per step (two steps) (Total: 6 female rats)

Control animals:

no

Details on study design:

The animals were marked for individual identification by tail painting.
Prior to the administration, a detailed clinical observation was made of all animals.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting, the animals were weighed and the test item was administered. Food was provided again approximately 3-4 hours post dosing.

All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhea, lethargy, sleep and coma.
At the end of the observation period, the animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally at a dosage of approx. 8 mL/kg bw. All animals were subjected to gross necropsy. All gross pathological changes were recorded.

Statistics:

No

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut off

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the end of the study.

Clinical signs:

other: All animals survived without showing any signs of toxicity.

Gross pathology:

At necropsy, no macroscopical findings were observed in any animal of any step.

Any other information on results incl. tables

Table1: Results per Step

Step	Sex/no.	Dose (mg/kg)	Number of animals	Number of intercurrent deaths
1	f/1-3	2000	3	0
2	f/4-6	2000	3	0

Table 2: Absolute Body Weights in g and Body Weight Gain in %

Animal no. / sex	g Day 1	g Day 8	g Day 15	% Day 1-15
Step 1 (2000 mg/kg bw)
1 / female	158	182	192	+22
2 / female	155	176	187	+21
3 / female	151	165	171	+13
Step 2 (2000 mg/kg bw)
4 / female	170	203	215	+26
5 / female	161	182	199	+24
6 / female	162	194	204	+26

Table 3: Macroscopical Findings - Individual Data

Animal no. / sex	Organ	Findings at the necropsy
1 / female	--	NAD
2 / female	--	NAD
3 / female	--	NAD
4 / female	--	NAD
5 / female	--	NAD
6 / female	--	NAD

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the condition of this test, a single oral application of Magnesium chloride hexahydrate to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality. The median lethal dose of Magnesium chloride hexahydrate after a single oral administration to female rats, observed over a period of 14 days, is 5000 mg/kg body weight (LD50 cut off).

Executive summary:

The study was performed according to the OECG guideline 423 and was GLP compliant.

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with Magnesium Chloride hexahydrate by oral gavage administration at a dosage of 2000 mg/kg body weight.

The test item was dissolved in a vehicle (Aqua ad injectionem (sterile water)) at a concentration of 0.4 g/mL and administered at a dose volume of 5 mL/kg.

The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

 

Throughout the 14-day observation period, all animals survived until the end of the study without showing any signs of toxicity and the weight gain of the animals was within the expected range. Also at necropsy, no macroscopical findings were observed in any animal of any step.

In conclusion, the median lethal dose of Magnesium chloride hexahydrate after a single oral administration to female rats, observed over a period of 14 days is 5000 mg/kg body weight (LD50 cut off).