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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2010-01-12 to 2010-03-12
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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 17 July 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EC No. 440/2008, L 142
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The testing using the guinea pig maximisation test protocol was completed before the LLNA 429 was formally adopted by the OECD on the 22 July 2010.

Test material

Constituent 1
Reference substance name:
Magnesium chloride hexahydrate
EC Number:
616-575-1
Cas Number:
7791-18-6
IUPAC Name:
Magnesium chloride hexahydrate
Specific details on test material used for the study:
- Name used in study report: Magnesium chloride hexahydrate
- Batch no.: M 1197
- Purity: 100.8%
- Colour: colourless
- Physical state: solid crystals
- Expiry date: 28 July 2012
- Storage: at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Crl:HA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles RIver, 97633 Sulzfeld, Germany
- Age at study initiation: Approximately 5 weeks old
- Weight at study initiation:354 - 408 g
- Housing: The animals were kept in groups inTerluran- cages on Altromin saw fibre bedding in an air-conditioned room.
- Diet: Free access to autoclaved hay and to Altromin 3122 maintenance diet for guinea pigs
- Water: Free access to tap water
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 55 ± 10%
- Air changes (per hr): At least 10 x/ hour

IN-LIFE DATES: From: 25 January 2010 To: 25 February 2010

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
in the preliminary test one animal was treated intradermally with concentrations of 5% and 2.5% of the test item. Two animals were treated topically with concentrations of 100% and 50% of the test item for 24 as well as 48 hours.
Based on the results of this preliminary test, a concentration of 5% was chosen for the intradermal application of the main test and a concentration of 50% was selected for the dermal induction.
A concentration of 50% was found to be the highest dose suspended in vehicle which did not cause any signs of irritation after topical treatment over 24 hours and therefore was chosen for the challenge application in the main test.
Challengeopen allclose all
Route:
other: topical
Vehicle:
physiological saline
Concentration / amount:
in the preliminary test one animal was treated intradermally with concentrations of 5% and 2.5% of the test item. Two animals were treated topically with concentrations of 100% and 50% of the test item for 24 as well as 48 hours.
Based on the results of this preliminary test, a concentration of 5% was chosen for the intradermal application of the main test and a concentration of 50% was selected for the dermal induction.
A concentration of 50% was found to be the highest dose suspended in vehicle which did not cause any signs of irritation after topical treatment over 24 hours and therefore was chosen for the challenge application in the main test.
No. of animals per dose:
Number of animals in the test group: 10
Number of animals in the negative control group: 5
NUmber of animals in the dose range finding study: 3
Details on study design:
RANGE FINDING TESTS:
1 animal was treated intradermally with a concentration of 5% (left side) and 2.5% (right side) of the test item, suspended in physiological saline 0.9% NaCl.
2 animals were treated topically with concentrations of 100% (left side) and 50% (right side) of the test item for 24 as well as for 48 hours.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 injections (intradermal), 1 topical application
- Exposure period: 7 days (intradermal) 48 hours (topical application)
- Test groups: 1
- Control group: 1
- Site: shoulder region
- Frequency of applications: 3
- Concentrations: 5% (intradermal induction), 50% (dermal induction)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 20
- Exposure period: 24 hours
- Test groups: 1
- Control group: 1
- Site: left flank (test item), right flank (control)
- Concentrations: 50%
- Evaluation (hr after challenge): Approximately 24 and 48 hours after removing the patch the skin reaction was observed and recorded
Challenge controls:
A patch loaded with 0.5 mL of the vehicle
Positive control substance(s):
yes
Remarks:
mercaptobenzothiazole

Results and discussion

Positive control results:
The sensitisation rate after application of the positive-control substance was 100% confirming the reliabiliy of the test system. For individual results see Table 2 in "Any other information on results incl. tables."

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Injection site 1
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
erythema grade 2 in 5/5 control
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Injection site 1
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
erythema grade 2 in 10/10 test animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: test group and control. Dose level: Injection site 1 . Total no. in groups: 15.0. Clinical observations: erythema grade 2 in 5/5 control and 10/10 test animals.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Injection site 1
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
oedema grade 2 in 10/10 test animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: test group and control. Dose level: Injection site 1. Total no. in groups: 15.0. Clinical observations: oedema grade 2 in 4/5 control and 10/10 test animals.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Injection site 1
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
oedema grade 1 in 1/5 control animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: Injection site 1. Total no. in groups: 15.0. Clinical observations: oedema grade 1 in 1/5 control animals.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Injection site 2
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
erythema grade 1 in 9/10 test animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Injection site 2. Total no. in groups: 15.0. Clinical observations: erythema grade 1 in 9/10 test animals.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Injection site 2
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
eschar in 8/10 test animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Injection site 2. Total no. in groups: 15.0. Clinical observations: eschar in 8/10 test animals.
Reading:
1st reading
Hours after challenge:
24
Group:
other: test and control group
Dose level:
Injection site 3
No. with + reactions:
2
Total no. in group:
15
Clinical observations:
erythema grade 2 in 1/5 control and 1/10 test animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: test and control group. Dose level: Injection site 3. Total no. in groups: 15.0. Clinical observations: erythema grade 2 in 1/5 control and 1/10 test animals.
Reading:
1st reading
Hours after challenge:
24
Group:
other: test and control group
Dose level:
Injection site 3
No. with + reactions:
10
Total no. in group:
15
Clinical observations:
erythema grade 1 in 1/5 control and 9/10 test animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: test and control group. Dose level: Injection site 3. Total no. in groups: 15.0. Clinical observations: erythema grade 1 in 1/5 control and 9/10 test animals.
Reading:
1st reading
Hours after challenge:
24
Group:
other: test and control
Dose level:
Injection site 3
No. with + reactions:
2
Total no. in group:
15
Clinical observations:
oedema grade 2 in 1/5 control and 1/10 test animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: test and control. Dose level: Injection site 3 . Total no. in groups: 15.0. Clinical observations: oedema grade 2 in 1/5 control and 1/10 test animals.
Reading:
1st reading
Hours after challenge:
24
Group:
other: test and control group
Dose level:
Injection site 3
No. with + reactions:
2
Total no. in group:
15
Clinical observations:
oedema grade 1 in 1/5 control and 2/10 test animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: test and control group. Dose level: Injection site 3. Total no. in groups: 15.0. Clinical observations: oedema grade 1 in 1/5 control and 2/10 test animals.
Reading:
1st reading
Hours after challenge:
24
Group:
other: test and control group
Dose level:
Injection site 3
No. with + reactions:
7
Total no. in group:
15
Clinical observations:
eschar in 1/5 control and 6/10 test animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: test and control group. Dose level: Injection site 3. Total no. in groups: 15.0. Clinical observations: eschar in 1/5 control and 6/10 test animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test and control group
Dose level:
Injection site 1
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
erythema grade 2 in 1/5 control and 3/10 test animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: test and control group. Dose level: Injection site 1. Total no. in groups: 15.0. Clinical observations: erythema grade 2 in 1/5 control and 3/10 test animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test and control group
Dose level:
Injection site 1
No. with + reactions:
11
Total no. in group:
15
Clinical observations:
erythema grade 1 in 4/5 control and 7/10 test animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: test and control group. Dose level: Injection site 1 . Total no. in groups: 15.0. Clinical observations: erythema grade 1 in 4/5 control and 7/10 test animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test and control group
Dose level:
Injection site 1
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
oedema grade 2 in 1/5 control and 3/10 test animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: test and control group. Dose level: Injection site 1. Total no. in groups: 15.0. Clinical observations: oedema grade 2 in 1/5 control and 3/10 test animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test and control group
Dose level:
Injection site 1
No. with + reactions:
11
Total no. in group:
15
Clinical observations:
oedema grade 1 in 4/5 control and 7/10 test animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: test and control group. Dose level: Injection site 1. Total no. in groups: 15.0. Clinical observations: oedema grade 1 in 4/5 control and 7/10 test animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Injection site 1
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
necrosis in 1/10 test animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Injection site 1. Total no. in groups: 15.0. Clinical observations: necrosis in 1/10 test animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test and control group
Dose level:
Injection site 1
No. with + reactions:
2
Total no. in group:
15
Clinical observations:
eschar in 1/5 control and 1/10 test animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: test and control group. Dose level: Injection site 1. Total no. in groups: 15.0. Clinical observations: eschar in 1/5 control and 1/10 test animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Injection site 2
No. with + reactions:
4
Total no. in group:
5
Clinical observations:
erythema grade 1 in 4/5 test animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Injection site 2. Total no. in groups: 15.0. Clinical observations: erythema grade 1 in 4/5 test animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test and control group
Dose level:
Injection site 3
No. with + reactions:
11
Total no. in group:
15
Clinical observations:
erythema grade 1 in 2/5 control and 9/10 test animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: test and control group. Dose level: Injection site 3. Total no. in groups: 15.0. Clinical observations: erythema grade 1 in 2/5 control and 9/10 test animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: test and control group
Dose level:
Injection site 3
No. with + reactions:
2
Total no. in group:
15
Clinical observations:
oedema grade 1 in 1/5 control and 1/10 test animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: test and control group. Dose level: Injection site 3. Total no. in groups: 15.0. Clinical observations: oedema grade 1 in 1/5 control and 1/10 test animals.
Reading:
other: Immediately after removing the patch
Hours after challenge:
48
Group:
other: test and control group
No. with + reactions:
3
Total no. in group:
15
Clinical observations:
Desquamation in 1/5 control animals, erythema grade 1 in 2/10 test animals
Remarks on result:
other: Reading: other: Immediately after removing the patch. . Hours after challenge: 48.0. Group: other: test and control group. Total no. in groups: 15.0. Clinical observations: Desquamation in 1/5 control animals, erythema grade 1 in 2/10 test animals.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Injection site 1
No. with + reactions:
4
Total no. in group:
5
Clinical observations:
Oedema grade in 4/5 control animals

Any other information on results incl. tables

Preliminary Test:

One animal was treated intradermally with concentrations of 5% and 2.5% of the test item. Two animals were treated topically with concentrations of 100% and 50% of the test item for 24 as well as 48 hours.

Based on the results of this preliminary test, a concentration of 5% was chosen for the intradermal application of the main test and a concentration of 50% was selected for the dermal induction.A concentration of 50% was found to be the highest dose suspended in vehicle which did not cause any signs of irritation after a topical treatment over 24 hours and therefore was chosen for the challenge application in the main test.

Main test:

Signs of irritation during the induction:

Intradermal Induction I (24 hours reading)

Injection site 1: erythema grade 2 in 5/5 control and 10/10 test,oedema grade 2 in 4/5 control and 10/10 test animals and oedema grade 1 in 1/5 control animals.

Injection site 2: erythema grade 1 in 9/10 test animal

eschar in 8/10 test animals.

Injection site 3: erythema grade 2 in 1/5 control and 1/10 test animals, erythema grade 1 in 1/5 control and 9/10 test animals, oedema grade 2 in 1/5 control and 1/10 test animals, oedema grade 1 in 1/5 control and 2/10 test animals and eschar in 1/5 control and 6/10 test animals.

Intradermal Induction I (48 hours reading):

Injection site 1: erythema grade 2 in 1/5 control and 3/10 test animals, erythema grade 1 in 4/5 control and 7/10 test animals, oedema grade 2 in 1/5 control and 3/10 test animals, oedema grade 1 in 4/5 control and 7/10 test animals, necrosis in 1/10 animals and eschar in 1/5 control and 1/10 test animals.

Injection site 2: erythema grade 1 in 4/5 test animals

injection site 3: erythema grade 1 in 2/5 control and 9/10 test animals, oedema grade 1 in 1/5 control and 1/10 test animals.

Dermal Induction II (48 hours exposure, occlusive):

Immediately after removing the patch: Desquamation in 1/5 control animals, erythema grade 1 in 2/10 test animasl.

24 hours after removing the patch: Eschar in 5/5 control and 10/10 test animals, erythema grade 1 in 1/10 test animals, desquamation in 1/10 test animals.

Challenge exposure:

No erythema was observed in any of the test animals at any time. Erythema grade 1 was observed after 24 hours in one animal of the control group. No oedema was observed in any animal at any time. There was no evidence of sensitisation in the test item group at the challenge and the percentageof animals sensitised was 0%.

The animals of the test group showed no reduced weight gain compared to historical data.

Table 1: Classification System:

Patch test reaction

 

Grade

No visible change

0

Discrete or patchy erythema

1

Moderate and confluent erythema

2

Intense erythema and swelling

3

Table 2: Frequency of Sensitisation in Positive-Control Animals

Hours Erythema grade 0 Erythema grade 1 Erythema grade 2 Erythema grade 3 Oedema grade 0 Oedema grade 1 Oedema grade 2 Oedema grade 3 % animals sensitised
24 0 6 4 0 4 6 0 0 100
48 0 3 7 0 10 0 0 0 100
72 0 7 3 0 10 0 0 0 100

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study it can be stated that the test item Magnesium chloride hexahydrate caused no reactions identified as sensitisating at the tested concentration.
Executive summary:

In a dermal sensitisation study conducted according to OECD guideline 406 with magnesium chloride hexahydrate (purity 100%) in 0.9% physiological saline, 10 female young adult Crl: HA- guinea pigs were tested using the method of the guinea pig maximisation test.

At the daily clinical observation the animals did not show any visible clinical symptoms and no mortality occurred.

During the induction phase slight signs of irritation were observed. These findings confirmed the validity of the study.

In the challenge phase no erythema was observed in any of the test animals at any time. Erythema grade 1 was observed after 24 hours in one animal of the control group. No oedema was observed in any animal at any time.

There was no evidence of sensitisation at the challenge and the percentage of animals sensitised was 0%.

The positive control mercaptobenzothiazole did induce an appropriate response.

 

Under the conditions of the present study, it can be stated that the test item Magnesium chloride hexahydrate caused no reactions identified as sensitising at the tested concentration.