Magnesium chloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 2010 till May 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

One female animal was slightly below 200 g but this animal was only of 2 g below the accepted range, it was included in the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

One female animal was slightly below 200 g but this animal was only of 2 g below the accepted range, it was included in the study.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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:

male/female

Details on test animals or test system and environmental conditions:

Species/strain: Healthy rats, WISTAR Crl: WI(Han) (Full-Barrier)
Source: Charles River, 97633 Sulzfeld, Germany
The female animals were nulliparous and non-pregnant.
Body weight at the beginning of the study: females: 198 - 222 g, males: 241 – 262 g
Age at the beginning of the study: females: 18 - 19 weeks old, males: 8 -9 weeks old
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 for rats and mice, free access to tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological control at regular
intervals), the animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding, adequate acclimatisation period.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

Aqua ad injectionem

Details on dermal exposure:

Approximately 24 hours before the test, the fur was removed from the dorsal area of the trunk by using an electric clipper. Care was taken to avoid abrading the skin, and only animals with healthy intact skin were used.
No less than 10 % of the body surface was cleared for the application.
The test item was applied at a single dose, uniformly over an area which was approx. 10 % of the total body surface.

Duration of exposure:

The test item was held in contact with the skin throughout a 24-hour period. At the end of the exposure period residual test item was not removed.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

Prior to the application, a detailed clinical observation was made of all animals.
All animals were observed for 14 days after dosing.
The animals were weighed on day 1 (prior to the application) 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). As soon as symptoms were noticed they were recorded. 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. Attention was directed to observations of tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma.
At the end of the observation period, the animals were sacrificed by an overdosage of pentobarbital injected intraperitoneally. All animals were subjected to gross necropsy. All gross pathological changes were recorded.

Statistics:

Signs of erythema and oedema were assessed using the scoring system laid down in OECD Guideline 404.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No

Clinical signs:

other: The test item showed slight signs of dermal irritation (slight scratches) after a single dose application for one female (n°14) on day 3 and 4. The clinical signs observed were seen only on the day of application and may partly be due to the stress induc

Gross pathology:

At necropsy, female no. 14 showed changes of the tissue on the large intestine, which was filled with liquid. As this finding was seen in only one animal and was not associated with any specific clinical signs, this finding was most probably not test item related.

Other findings:

No

Any other information on results incl. tables

Absolute Body Weights in g and Body Weight Gain in %

Animal No. / Sex	Day 1	Day 8	Day 15	% Day 1 - 15
11 female	222	219	219	-1
12 female	201	208	213	6
13 female	218	216	215	-1
14 female	214	217	215	0.5
15 female	198	195	200	1
21 male	262	288	315	20
22 male	256	275	303	18
23 male	241	268	291	21
24 male	244	264	286	17
25 male	247	273	302	22

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the dermal LD50 was determined to be > 2000 mg Magnesium chloride hexahydrate/kg body weight.

Executive summary:

This study was a limit test of the acute dermal method (OECD 402) in male and female Wistar rats carried out according to the OECD guideline 402.

Under the conditions of the present study, single dermal application of the test item Magnesium chloride hexahydrate to rats at a dose of 2000 mg/kg body weight was associated with slight signs of toxicity and irritation, but no mortality.

The dermal LD50 was determined to be > 2000 mg Magnesium chloride hexahydrate/kg body weight.