Registration Dossier

Diss Factsheets

Administrative data

Description of key information

In the key in vivo (non-LLNA) skin sensitisation study, conducted according to an appropriate OECD test guideline and in compliance with GLP,  the test material octaphenylcyclotetrasiloxane was reported to be not sensitising to skin (Eurofins, 2017).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 June 2017 to 10 August 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
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.
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: The test material was applied neat and undissolved.
- 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 preparation of the test item and the determination of the dose levels followed the procedures indicated in the OECD guideline 406. 100% concentration of the test item was used for the first, second and third induction as well as challenge.
- Preliminary purification step (if any): No
- Final dilution of a dissolved solid, stock liquid or gel: Not specified
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 4–5 weeks old
- Weight at study initiation: 333–378 g
- Housing: The animals were kept in groups in Terluran - cages on Altromin saw fibre bedding.
- 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: at least 5 days
- Indication of any skin lesions:

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
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 % concentration (0.5 g of the test substance)
Day(s)/duration:
6 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 % (0.5 g test substance)
Day(s)/duration:
6 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Test group animals: 20
Negative-control animals: 10
Details on study design:
RANGE FINDING TESTS: The adequate concentrations for the inductions and the challenge were determined by a preliminary test. A concentration of 100 % (neat) of the test sample was applied topically to the flanks of 2 animals for 6 hours using occlusive dressings.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three induction exposures
- Exposure period: 3 weeks
- Test groups: A gauze patch was loaded with 0.5 g of the test substance. The patch was applied to the test area of approximately 2.5 x 2.5 cm and was held in contact with the help of an occlusive dressing for 6 hours.
- Control group: A dry gauze patch was applied to the test area of approximately 2.5 x 2.5 cm and was held in contact with the help of an occlusive dressing for 6 hours.
- Site: left flank
- Frequency of applications: Once a week at the same test area at weekly intervals for 3 weeks.
- Duration: 6 hours
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: 14 days after the last induction application
- Exposure period: 1 day
- Test groups: 0.5 g of the test substance was applied to an area of approximately 2.5 x 2.5 cm on the right flank and was held in contact with the help of an occlusive dressing for 6 hours.
- Control group: 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.
- Site: left and right flanks
- Concentrations: 100%
- Evaluation (hr after challenge): 24 and 48 hours after patch removal.

OTHER:
Challenge controls:
The dry gauze patches served as negative control.
Positive control substance(s):
yes
Remarks:
mercaptobenzothiazole, purity  98%,
Positive control results:
The sensitisation rate after application of the positive-control substance mercaptobenzothiazole (25% in vaseline) was 65%, confirming the reliability of the test system.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Dry patch
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:
Dry patch
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

Based on the results of this preliminary test, a concentration of 100% was selected for the dermal inductions. This concentration did not cause any signs of irritation or systemic effects. Therefore, a concentration of 100% was also chosen for the challenge application in the main test.

Interpretation of results:
GHS criteria not met
Conclusions:
In the in vivo (non-LLNA) skin sensitisation study, conducted according to an appropriate OECD test guideline and in compliance with GLP, the test material octaphenylcyclotetrasiloxane was reported to be not sensitising to skin.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In the key in vivo (non-LLNA) skin sensitisation study, conducted according to an appropriate OECD test guideline and in compliance with GLP,  the test material octaphenylcyclotetrasiloxane was reported to be not sensitising to skin (Eurofins, 2017).

Prior to each induction application, the left flank was cleared of hair (close-clipped). Then, a gauze patch was loaded with 0.5 g of 100% of the test substance. The patch was applied to the test area of approximately 2.5 x 2.5 cm and was held in contact with the help of an occlusive dressing for 6 hours. This procedure was repeated once a week at the same test area at weekly intervals for 3 weeks. The negative control group was treated the same way, but a dry gauze patch was applied to the test area.

At challenge, 14 days after the last induction application both flanks were cleared of hair (close-clipped). Then, 0.5 g of 100% of the test substance was applied to an area of approximately 2.5 x 2.5 cm on the right flank and was held in contact with the help of an occlusive dressing for 6 hours. 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. Within approximately 21 hours after removing the patch, the challenge area was cleaned and cleared of hair by the use of a depilatory cream. Approximately 24 and 48 hours after removing the patch the skin reaction was observed and recorded. There was no evidence of sensitisation and the percentage of sensitised animals was 0%.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data for octaphenylcyclotetrasiloxane, no classification for skin sensitisation is required according to Regulation (EC) No 1272/2008.