Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August - September 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to current OECD guideline and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
The Buehler type of sensitization test was selected since the test substance is a functional silane and the Local Lymph Node Assay as preferred alternative has shown to provide false positive results for silicone substances.
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: Young adult animals (approx. 4 weeks old)
- Weight at study initiation: Not determined
- Housing: Group housing of maximally 5 animals per labelled Noryl cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): min. 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Induction - undiluted
Challenge - undiluted
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Induction - undiluted
Challenge - undiluted
No. of animals per dose:
20 test animals, 10 negative controls, 10 positive controls
Details on study design:
RANGE FINDER

A preliminary irritation study was conducted in order to select test substance concentrations to be used in the Main Study. The selection of concentrations was based on the following criteria:
- The concentrations are well-tolerated by the animals.
- For the induction exposures: the highest possible concentration that produced mild irritation
(grade 2).
- For challenge exposure: the maximum non-irritant concentration.
The starting- and subsequent concentrations were taken from the series: 100% (undiluted), 50%, 20%, 10%, 5%, 2%, 1%.

INDUCTION

Epidermal application:
A series of four test substance concentrations was used, the highest concentration being the maximum concentration that could technically be applied. Two different concentrations were applied (0.5 mL each) per animal to the clipped flank using patches (2x3 cm) mounted on Medical
tape, which will be held in place with Micropore tape and subsequently Coban elastic bandage. After 6 hours, the dressings were removed and the skin cleaned of residual test substance with water. The resulting dermal reactions were assessed for irritation 24 and 48 hours after removal of the last
dressing. The control animals were treated the same except with vehicle alone.

CHALLENGE

The challenge dose was applied on Day 28. The right flank of all animals was clipped and subsequently treated epidermally with the undiluted test
substance and the vehicle (0.1 mL of each), using Patch Test Plasters. The patches were held in place with Micropore tape and subsequently Coban
elastic bandage. After 6 hours, the dressings were removed and the skin cleaned of residual test substance and vehicle using water. The treated sites were assessed for challenge reactions 24 and 48 hours after removal of the last dressing. After termination, animals were sacrificed using isoflurane and an intra-peritoneal injection of Euthasol 20% .

INTERPRETATION

The results for the experimental animals at the challenge phase were compared with the results for the control animals. All skin reactions were considered signs of sensitization provided that such reactions were less severe or are less persistent in the control group. A sensitization rate (%) was calculated for each concentration as follows: the number of sensitized animals at one concentration as a proportion of the total number of animals of the experimental group.

Positive control substance(s):
yes
Remarks:
ALPHA- HEXYLCINNAMALDEHYDE

Results and discussion

Positive control results:
50% dose, 6/10 animals wiht reactions which were still present at 48 hours.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: induction & challenge
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
The readings were 0 in all animals at all dose levels at all time points.
Remarks on result:
other: see Remark
Remarks:
Reading: other: induction & challenge. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: The readings were 0 in all animals at all dose levels at all time points..
Reading:
other: induction & challenge
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
The readings were 0 in all animals at all dose levels at all time points.
Remarks on result:
other: see Remark
Remarks:
Reading: other: induction & challenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: The readings were 0 in all animals at all dose levels at all time points..

Any other information on results incl. tables

The induction and challenge readings were 0 in all animals at all dose levels at all time points. The total number of animals in the test group was 20 and in the negative control group, 10.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was found to be not sensitising to guinea pig skin in a Buehler test, with no skin reactions evident in any of the test animals and appropriate positive and negative controls in place. The study was conducted according to OECD TG 406 and in compliance with GLP.