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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:
key study
Study period:
16 March 2017 to 08 June 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
An LLNA study was not performed because the test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, protected from light
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: Stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test material was dissolved in acetone. For the challenge 5 g of the test item was dissolved in with the vehicle to give a final volume of 20 g and to achieve a 25% concentration. The solution was prepared 30 minutes before application.
- Preliminary purification step (if any): None specified.
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Crl:HA
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Germany
- Females (if applicable) nulliparous and non-pregnant: not applicable
- Microbiological status of animals, when known: healthy
- Age at study initiation: approximately 5–6 weeks old
- Weight at study initiation: 308–375 g
- Housing: Semi barrier in an air-conditioned room
- Diet: autoclaved hay and to Altromin 3122 maintenance diet for guinea pigs, rich in crude fibre, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 5 days
- Indication of any skin lesions: none reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): at least 10 x / hour
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark
:

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
100%
Day(s)/duration:
Occlusive dressing kept in contact with the skin for 6 hours; induction repeated once a week for three consecutive weeks
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
25%
Day(s)/duration:
Occlusive dressing kept in contact with the skin for 6 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Test group: 20 animals
Negative control: 10 animals
Details on study design:
RANGE FINDING TESTS: 5 animals were used for the preliminary test. The adequate concentrations for the inductions and the challenge were determined by a preliminary test with different concentrations. The test item was applied topically at 5 different concentrations (12.5%, 25%, 50% and 75%, each diluted with the vehicle acetone and 100%, neat) were applied topically to the flanks of the animals for 6 hours using occlusive dressings. Based on the results of this preliminary test 100% was the selected concentration for dermal induction and 25% for the challenge application.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 exposures
- Exposure period: 3 weeks
- Test groups: Test groups treated with 100% test substance.
- Control group: Treated with acetone.
- Site: Flanks
- Frequency of applications: Once a week
- Duration: 6 hours
- Concentrations: 100% test substance

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: 14 days after last induction
- Exposure period: 6 hours
- Test groups: The right flanks of 20 animals were treated with 0.5 mL of 25% test item in acetone.
- Control group: The left flanks of 10 animals were treated with 0.5 mL of acetone only.
- Site: Both flanks
- Concentrations: 25% test item in acetone
- Evaluation (hr after challenge): at 24 and 48 hours

Challenge controls:
A patch loaded with 0.5 mL of the vehicle was applied to an area of approximately 2.5 x 2.5 cm on the left flank at an untreated site (intraspecific control) and was held in contact with the help of an occlusive dressing for 6 hours.
Positive control substance(s):
yes

Results and discussion

Positive control results:
The sensitisation rate after application of the positive-control substance mercaptobenzothiazole (25% in vaseline) was 80%, confirming the reliability of the test system.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25 % in acetone
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
Erythema grade 2 was observed in 1/20 test animals
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
Erythema grade 2 was observed in 1/20 test animals
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
acetone
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
acetone
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
mercaptobenzothiazole
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
65% of positive control animals showed skin sensitisation
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
mercaptobenzothiazole
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
60% of positive control animals showed skin sensitisation
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In the in vivo skin sensitisation study, conducted according to an appropriate OECD test guideline and in compliance with GLP, the test material (1,1,3,3-tetramethyldisiloxane-1,3-diyl)dipropane -1,3-diyl dimethacrylate was concluded to be not sensitising to skin.