Trimethoxy(2,4,4-trimethylpentyl)silane

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 October - 01 December 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

BAYERISCHES LANDESAMT FÜR ARBEITSSCHUTZ, ARBEITSMEDIZIN UND SICHERHEITSTECHNIK, München, Germany

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study was done before LLNA method was first choice.

Test material

Test material information

Constituent 1

Reference substance name:

Triethoxy(2,4,4-trimethylpentyl)silane

EC Number:

252-558-1

EC Name:

Triethoxy(2,4,4-trimethylpentyl)silane

Cas Number:

35435-21-3

Molecular formula:

C14H32O3Si

IUPAC Name:

triethoxy(2,4,4-trimethylpentyl)silane

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Strain: Hsd Poc: DH Guinea pigs
- Source: Harlan Winkelmann GmbH (Borchen, Germany)
- Weight at study initiation: 300- 500 g
- Housing: in groups of max. 10 in Terluran cages on Altromin saw fiber bedding
- Diet: Altromin 3122 maintenance diet for guinea pigs, rich in crude fiber, totally-pathogen-free-TPF, ad libitum
- Water: tap water, ad libitum
- Acclimation period: adequate

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22±3 °C
- Humidity (%): 55±10%
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12 (artificial light from 6.30-18.30)

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

cotton seed oil

Concentration / amount:

For the intradermal injection (induction stage), 0.5 ml of the test item (purity 98.53%) was diluted with 9.5 ml of cotton seed oil (= 5%).

Day(s)/duration:

Day 0

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Induction 2

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

For topical applications the test item was applied at a 100% concentration.

Day(s)/duration:

Day 6/48 h topical application

Adequacy of induction:

non-irritant substance, but skin pre-treated with 10% SDS

Challenge

Route:

epicutaneous, occlusive

Vehicle:

cotton seed oil

Concentration / amount:

100%

Day(s)/duration:

Day 20/24 h topical application

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10/test group, 5/control group

Details on study design:

RANGE FINDING TESTS:
For the justification of dose levels a preliminary test was performed. Four animals were topically treated with 25%, 50%, and 100% concentration of the test item. No signs of irritation and systemic toxicity were recorded after a contact period of 48 h after application of 100% concentration. Therefore, the 100% concentration was chosen for the topical induction and for the challenge as well.
For the justification of the first stage of the induction three animals were intradermally treated with 1%, 2.5%, and 5%. Slight erythema was found in the animal treated with the 5% concentration. These symptoms lasted until 48 h after application. No other signs of irritation and systemic toxicity were recorded until 72 h after application. Therefore, the highest concentration (5%) was chosen for the intradermal induction.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections) on day 0:
Injection 1: a 1+1 mixture (v/v) FCA/isotonic saline
Injection 2: prepared test item
Injection 3: prepared test item at a concentration of 50% (v/v) in FCA, 1+1 (v/v) diluted with isotonic saline
Epicutaneous on day 6: 0.5 ml of the test item (100%)
- Control group:
Intradermal (3 pairs of injections) on day 0:
Injection 1: a 1+1 mixture (v/v) FCA/isotonic saline
Injection 2: vehicle
Injection 3: vehicle at a concentration of 50% (v/v) in FCA, 1+1 (v/v) diluted with isotonic saline
Epicutaneous on day 6: 0.5 ml of the vehicle
- Site: shoulder region
- Frequency of applications: every 6 days
- Duration: days 0-6
- Concentrations: intradermal 5%, epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20
- Exposure period: 24 h
- Test groups: 0.5 ml of 100% test substance
- Control group: 0.5 ml of 100% test substance
- Site: flank
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48, and 72 h

OTHER: During challenge the patches were held in contact by occlusive dressing. At the end of the challenge skin was cleaned with the aid of moistened gauze patches.

Challenge controls:

The control group is actually a challenge control.

Positive control substance(s):

yes

Remarks:

Mercaptobenzothiazole, purity > 98% (historical positive control data; the latest check was performed in August/September 2000)

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

intradermal induction: 5%; challenge: 100%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

intradermal induction: 5%; challenge: 100%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

intradermal induction: 0%; challenge: 100%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

intradermal induction: 5%; challenge: 100%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None

Results 5

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

Remarks:

tested on regular basis in the laboratory

Any other information on results incl. tables

After intradermal injection of the test item slight erythema (grade 1) were observed in all animals.

Applicant's summary and conclusion

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 tested for skin sensitisation according to OECD TG 406 (Guinea Pig Maximization Test) and in compliance with GLP. There were no signs of sensitisation recorded for any of the tested animals. Based on these findings classification for skin sensitisation according to Regulation (EC) No. 1272/2008 is not warranted.