Registration Dossier

Administrative data

Description of key information

Skin sensitisation (according to OECD 406 / Buehler Test): negative

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:
04 Dec 2012 - 13 Feb 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1992)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
(2003)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Erlangen, Germany
Type of study:
Buehler test
Justification for non-LLNA method:
The Buehler type of sensitization test was selected since the test substance is a functional silane and the Local Lymph Node Assay as the preferred alternative has shown to provide false positive results for silicone substances.
Species:
guinea pig
Strain:
other: Hartley (Crl:HA-Guinea Pigs (full barrier))
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approximately 4 weeks old
- Weight at study initiation: 301-377 g
- Housing: in groups in Terluran-cages on Altromin saw fibre bedding (lot no. 011012)
- Diet: autoclaved hay and Altromin 3122 maintenance diet for guinea pigs (lot no. 1311/0807), rich in crude fibre, ad libitum
- Water: tap water (drinking water, municipal residue control, microbiological controls at regular intervals), ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55±10
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% (neat test material)
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
No. of animals per dose:
- 2 for the preliminary test
- 20 in the test group of main study
- 10 in the negative control goup of the main study
Details on study design:
RANGE FINDING TESTS:
2 animals were treated topically with concentrations of 50% and 100% of the test item (suspended with vaseline) for 6 hours. Vaseline was chosen as vehicle due to its non-irritating characteristics. Based on the results of this preliminary test the following concentrations were chosen for the main test:
- 100% for the dermal inductions
- 100% for the challenge application

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: a gauze patch loaded with 0.5 ml of the neat test substance
- Control group: a dry gauze patch, as no vehicle was used in the main study
- Site: left flank
- Frequency of applications: once a week
- Duration: Days 1-15
- Concentrations: 100% (undiluted)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6 h
- Test groups: a gauze patch loaded with 0.5 ml of the neat test substance (right flank) and a dry gauze patch, as no vehicle was used in the main study (left flank)
- Control group: a gauze patch loaded with 0.5 ml of the neat test substance (right flank) and a dry gauze patch, as no vehicle was used in the main study (left flank)
- Site: right and left flanks
- Concentrations: 100% (undiluted)
- Evaluation (hr after challenge): 24 and 48 h
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
The recent reliability check was performed in October/November 2012: mercaptobenzothiazole (purity 98%), 50% in vaseline (induction) and 25% in vaseline (challenge)
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Remarks:
positive control is checked in laboratory on regular basis

Preliminary Test

2 animals were treated topically with concentrations of 50% and 100% of the test item (suspended with vaseline) for 6 hours. Based on the results of this preliminary test, a concentration of 100% was selected for the inductions as well as for the challenge. This concentration did not cause any signs of irritation after a topical treatment over a period of 6 hours.

Main Test

Dermal Induction I, II and III (6-hour exposure, occlusive):

- Immediately after removing the patch: no signs of irritation were observed in any of the animals

- 24 hours after removing the patch: no signs of irritation were observed in any of the animals

Challenge Exposure (6-hour exposure, occlusive):

- The results of the test animals at the challenge phase were compared to the results of the control animals. Neither erythema nor oedema was observed in any animal at any time of observation. There was no evidence of sensitisation and the percentage of sensitised animals was 0%.

- All animals of both groups survived throughout the test period. No signs of toxicity were recorded. The body weight development was within the biological range for all animals compared to historical data.

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was investigated for skin sensitising potential in a Buehler Test conducted in accordance with OECD TG 406 and in compliance with GLP. There were no signs of skin reactions after induction and challenge with the neat test material in any of the animals. Therefore, the test item is concluded to be not sensitising under the conditions of this test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In the available key study (BSL BIOSERVICE, 2013), the test substance was investigated for its skin sensitising potential in a Buehler Test according to the OECD test guideline 406, and in compliance with GLP. During the induction phase gauze patches with 0.5 ml of the neat test item were topically applied to the clipped flanks of 20 female Hartley guinea pigs once a week for three consecutive weeks, and were held in contact under occlusive conditions for 6 h. 10 female animals of the control group were subsequently treated in the same way with a dry gauze patch. For challenge exposure all animals of the control and test groups received a gauze patch loaded with 0.5 ml of the neat test material on the clipped right flank and a dry gauze patch on the clipped left flank. The patches were held in contact with the skin under occlusive conditions for 6 h. 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. Additionally all animals were observed for signs of toxicity at least once daily during the test period. Neither erythema nor oedema was observed in any animal at any time of observation. There was no evidence of sensitisation and the percentage of sensitised animals was 0%. All animals of both groups survived throughout the test period. No signs of toxicity were recorded. The body weight development was within the biological range for all animals compared to historical data. The sensitivity of the strain was proven in the recent reliability check performed in October/November 2012. The test item is therefore concluded to be not sensitising to the skin under the conditions of this test.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data is reliable and suitable for classification. Based on this data, classification for skin sensitisation according to EC/1272/2008 is not warranted.