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Description of key information

In the key in vivo skin sensitisation study, conducted according to an appropriate OECD test guideline and in compliance in GLP, the test substance, amino functional alkoxysilanes (reaction mass of tri-(methoxy/ethoxy)-methylsilane and amino-functional(methoxy/ethoxy)-silanes), was reported to be 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 September 2016 to 16 March 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, protected from moisture
- Stability under test conditions: undergoes hydrolysis in water at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: The test material was dissolved in acetone.
- 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: For the challenge 0.62 g of the test item was dissolved in acetone to give a final volume of 20 mL and to achieve a 3.1% concentration. The solution was prepared 55 minutes before application.
- Preliminary purification step (if any): not specified
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable

FORM AS APPLIED IN THE TEST (if different from that of starting material): liquid

Species:
guinea pig
Strain:
other: Crl:HA
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Germany
- Microbiological status of animals, when known:
- Age at study initiation: approximately 5-6 weeks old
- Weight at study initiation: 302-389 g
- Housing: The animals were kept in groups of 5 animals in Terluran - cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): autoclaved hay and Altromin 3122 maintenance diet for guinea pigs, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: none specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): 12 / 12
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
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:
other: acetone
Concentration / amount:
3.1%
Day(s)/duration:
6 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Preliminary test: 8
Test group: 20
Negative control group: 10
Details on study design:
RANGE FINDING TESTS: The adequate concentrations for the inductions and the challenge were determined by a preliminary test with different concentrations. Either the undiluted test sample or each of two concentrations of the test sample diluted with the vehicle were applied topically to the flanks of the animals for 6 hours using occlusive dressings. Two animals were treated with each concentration. As the test item was irritating, the highest concentration to cause mild irritation for each induction exposure and the highest non-irritating concentration for the challenge exposure were determined.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three induction exposures
- Exposure period: 6 hours
- Test groups: A Hill Top Chamber was loaded with 0.5 ml of 100% test substance. Then it was applied to the test area of approximately 2.5 x 2.5 cm and was held in contact with the help of hypoallergenic surgical tape and hypoallergenic elastic bandage for 6 hours.
- Control group: Hill Top Chamber was applied to the negative control group
- Site: the left flank
- Frequency of applications: once a week for three weeks
- Duration: 6 hours
- Concentrations: 100 % test item

B. CHALLENGE EXPOSURE
- No. of exposures: One exposure
- Day(s) of challenge: 14 days after the last induction.
- Exposure period: 6 hours
- Test groups: 0.5 mL of the prepared test substance was loaded on a Hill Top Chamber and 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 dressings.
- Control group: A Hill Top Chamber was loaded with 0.5 mL of the vehicle and was applied to the left flank at an untreated site and was held in contact with the help of an occlusive dressing.
- Site: left flank
- Concentrations: 3.1% in acetone
- Evaluation (hr after challenge): 24 and 48 hours

Challenge controls:
A Hill Top Chamber loaded with 0.5 mL of the vehicle was applied to an area of approx. 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
Remarks:
mercaptobenzothiazole, purity > 98%
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.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
3.1% test substance in acetone
No. with + reactions:
13
Total no. in group:
20
Clinical observations:
2 animals with erythema grade 2; 11 animals with erythema grade 1
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% acetone (vehicle)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
3.1% test substance in acetone
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
3.1% test substance in acetone
No. with + reactions:
13
Total no. in group:
20
Clinical observations:
2 animals with erythema grade 2;11 animals with erythema grade 1.
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% acetone (vehicle)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
3.1 % test substance in acetone
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
In the skin sensitisation study, conducted according to an appropriate OECD test guideline and in compliance in GLP, the test substance, amino functional alkoxysilanes (reaction mass of tri-(methoxy/ethoxy)-methylsilane and amino-functional(methoxy/ethoxy)-silanes), was reported to be sensitising to skin.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Amino functional alkoxysilanes is a multiconstituent substance which is the reaction mass of tri-(methoxy/ethoxy)methylsilane and amino-functional (methoxy/ethoxy)-silanes. The identity and abundance of the constituents have been determined by GC analysis. A detailed description of the composition can be found in Section 1.2 of the Chemical Safety Report; in broad terms the composition can be described as shown in Section 5.2.

In the key in vivo skin sensitisation study, conducted according to an appropriate OECD test guideline and in compliance in GLP, the test substance, amino functional alkoxysilanes (reaction mass of tri-(methoxy/ethoxy)-methylsilane and amino-functional(methoxy/ethoxy)-silanes), was reported to be sensitising to skin (Eurofins, 2017).

At induction, a Hill Top Chamber was loaded with 0.5 mL of undiluted test substance. Then it was applied to the test area of 20 test guinea pigs and held in contact with the skin for 6 hours. This procedure was performed once a week for three weeks. Erythema grade 1 was observed in 18 out of 20 test animals at 24 hours after induction I, all animals after induction II and 17 out of 20 animals after induction III. Erythema grade 2 was observed in 3 out of 20 test animals 24 hours after induction III. No signs of irritation were observed in the negative control animals as well as in 2 out of 20 test animals 24 hours after induction.

14 Days after the last induction, both flanks were cleared of hair and prepared for challenge application. At challenge, 0.5 mL of 3.1% test substance was loaded on a Hill Top Chamber and applied to the area for 6 hours under occlusive dressing. The same procedure was performed for the vehicle. Erythema grade 2 was observed in 2 out of 20 test animals and erythema grade 1 in 11 out of 20 test animals at 24 and 48 hours after challenge. The percentage of sensitised animals was 65% and therefore the test substance was concluded to be a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available in vivo skin sensitisation data for the registered substance amino functional alkoxysilanes (reaction mass of tri-(methoxy/ethoxy)-methylsilane and amino-functional(methoxy/ethoxy)-silanes), the registration substance is classified as Skin Sens. Cat. 1A according to Regulation (EC) No. 1272/2008.

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