Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2009-11-10 to 2009-12-02
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
, 2001-12-17
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2009-04-06
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Magnesium chloride
EC Number:
232-094-6
EC Name:
Magnesium chloride
Cas Number:
7786-30-3
IUPAC Name:
magnesium dichloride
Constituent 2
Reference substance name:
7791-18-6
Cas Number:
7791-18-6
IUPAC Name:
7791-18-6
Constituent 3
Reference substance name:
magnesium chloride hexahydrate
IUPAC Name:
magnesium chloride hexahydrate
Test material form:
solid: crystalline
Details on test material:
- 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:
TEST ANIMALS (The animals were derived from a controlled full barrier maintained breeding system (SPF). According to Art. 9.2, No.7 of the German Act of Animal Welfare the animals were bred for experimental purposes.)
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8 - 12 weeks old
- Weight at study initiation: Animals no. 1 - 3, step 1: 151 - 158 g; Animals no. 4 - 6, step 2: 161 -170 g
- Fasting period before study: Prior to administration food was withhel from the test animals for 16 to 19 hours (access to water was permitted). Food was provided again approximately 3 -4 hours post dosing.
- Housing: full-barrier in an air-conditioned room; The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 06.06.09)
- Diet: Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1452)
- Water: Free access to tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, multicipal residue control, microbiological control at regular intervals.)
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Air changes: 10x / hour
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
Aqua ad injection (sterile water, B. Braun Melsungen, lot no. 7494A191, expiry date: 11.2010)
- Justification for choice of vehicle: This vehicle was chosen due to its non-toxic characteristics.

DOSAGE PREPARATION: The test item was weighed out into a tared vial on a precision balance. A solution with the vehicle (Aqua ad injectionem (sterile water)) was prepared.
For all animals of the first and second step, 2 g of the test item were dissolved in the vehicle to gain a final volume of 5 mL and to achieve a dose of 2000 mg/kg body weight at a dose volume of 5 mL/kg body weight. The test item was administered at a dose volume of 5 mL/kg body weight.
The dose formulations were made shortly before each dosing occasion.
No further information on the oral exposure was stated.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
3 female rats per step (Total: 6 female rats)
Control animals:
no
Details on study design:
- Duration of observation period following administration: All animals were observed for 14 days after dosing for general clinical signs morbidity and mortality.
- Frequency of observations and weighing: Prior to the administration a detailed clinical observation was made of all animals. Following the period of fasting the animals were weighed and the test item was administered. The animals were also weighed on days 8 and 15 after administration. A careful clinical examination was maade several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hoours 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, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: Yes
At the end of the observation period the animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally (Narcoren®, manufacturer: Merial; lot no.: 193089; expiry date: 08.2012) at a dosage of approx. 8 mL/kg bw.
All animals were subjected to gross necropsy. All gross pathological changes were recorded.
No further information on the study design was stated.
Statistics:
No data

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut off value: 5000 mg/kg body weight
Mortality:
No mortality was observed.
Clinical signs:
No signs of toxicity were observed in any of the animals.
Body weight:
None of the animals showed weight loss during the observation period.
Gross pathology:
No special gross pathological changes were recorded for any animal.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present study, a single oral application of the test item 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 :
LD50 cut off (rat): 5000 mg/kg body weight.
According to the Regulation (EC) No 1272/2008 and subsequent regulations, the test item is not acutely toxic via the oral route.