[3-(2,3-epoxypropoxy)propyl]triethoxysilane

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10.10.2005 to 18.11.2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study was conducted according to an appropriate OECD test guideline, with acceptable restrictions. The restriction was that sodium lauryl sulfate was not used in the topical induction phase; the guideline recommends that this substance be applied before the test substance, for non-irritating substances.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

No sodium lauryl sulfate applied during induction phase.

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Buehler/Guinea Pig Maximisation test method. Furthermore, the LLNA test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.

Test material

Test material information

Constituent 1

Reference substance name:

[3-(2,3-epoxypropoxy)propyl]triethoxysilane

EC Number:

220-011-6

EC Name:

[3-(2,3-epoxypropoxy)propyl]triethoxysilane

Cas Number:

2602-34-8

Molecular formula:

C12-H26-O5-Si

IUPAC Name:

triethoxy[3-(oxiran-2-ylmethoxy)propyl]silane

Details on test material:

- Name of test material (as cited in study report): A-1871
- Substance type: Alkoxysilane
- Physical state: Amber liquid
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature, protected from moisture in a cool dry area.

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Age at study initiation: No data
- Weight at study initiation: 300-500 g
- Housing: Groups in Terluran cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Described as 'adequate'

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3
- Humidity (%): 55 ±10
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17.10.2005 To: 18.11.2005

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

cotton seed oil

Induction 2

Concentration / amount:

Intradermal induction: 10% in cottonseed oil
Topical induction and challenge: 100% (neat)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

cotton seed oil

Challenge 2

Concentration / amount:

Intradermal induction: 10% in cottonseed oil
Topical induction and challenge: 100% (neat)

No. of animals per dose:

Test: 10
Negative ontrol: 5

Details on study design:

RANGE FINDING TESTS: Two animals were intradermally treated with 10, 25, 50 and 100% test substance in cottonseed oil. For the 100 and 50% concentration grade 2 erythema at 24 and 48 hours, and grade 1 erythema at 72 hours were recorded. Both concentrations showed grade 1 oedema at 24 and 72 hours. For the 100 and 50% concentrations necrosis was recorded at all observation points.
For the 25% concentration grade 1 erythema and oedema were recorded at all observation times.
For the 10% concentration grade 1 erythema was observed at 24, 48 and 72 hours. Grade 1 oedema was recorded at 48 hours.

Therefore the concentration of 10% was chosen for the intradermal induction.

Two animals were topically treated with 50 as well as 100% concentration for 24 and 48 hours, respectively. There were no signs of irritation, therefore the 100% concentration was used for the topical induction as well as the challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: Topical application was for 48 hours
- Test groups: Three injections as follows:
Injection 1: Freund's Complete Adjuvant, 1+1 (v/v) diluted with isotonic saline.
Injection 2: Prepared test substance
Injection 3: Prepared test substance at a concentration of 50% (v/v) in Freund's Complete Adjuvant, 1+1 (v/v) diluted with isotonic saline.

For topical induction: 0.5 ml of test substance applied for 48 hours under an occlusive dressing.

- Control group: Three injections as follows:
Injection 1: Freund's Complete Adjuvant, 1+1 (v/v) diluted with isotonic saline.
Injection 2: Vehicle at a concentration of 100%
Injection 3: Vehicle at a concentration of 50% (v/v) in Freund's Complete Adjuvant, 1+1 (v/v) diluted with isotonic saline.

For topical induction 0.5 ml vehicle applied for 48 hours under an occlusive dressing.
- Site: Shoulder region
- Frequency of applications: Intradermal injection on Day 0; Topical induction on Day 7.

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Day 20
- Exposure period: 24 hours
- Test groups: 0.5 ml test substance applied under occlusive dressing
- Control group: 0.5 ml test substance applied under occlusive dressing
- Site: Flank
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48 and 72 hours after removal of the patches

OTHER: All animals were observed for signs of toxicity daily during the test period.

Challenge controls:

Negative control: 0.5 ml neat test substance applied as for the test group.

Positive control substance(s):

no

Remarks:

but sensitising substance (mercaptobenzothiazole results presented) have been tested at the laboratory and have proven the sensitivity of the test.

Results and discussion

Positive control results:

Historical controls confirmed the sensitivity of the test.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No clinical signs of toxicity.

Remarks on result:

no indication of skin sensitisation

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

No clinical signs of toxicity.

Remarks on result:

no indication of skin sensitisation

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

Mercaptobenzothiazole 15%

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

Mercaptobenzothiazole 15%

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Conclusions:

In a guinea pig maximisation study conducted according to a protocol similar to OECD 406 (sodium lauryl sulfate not used in topical induction for this non-irritating substance) and in compliance with GLP (reliability score 2) [3-(2,3-epoxypropoxy)propyl]triethoxysilane was not sensitising to skin of guinea pigs.