Trimethoxyoctadecylsilane

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 Aug 2004 to 15 Sep 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

The test was performed in 2004 when the OECD Guideline 406 adopted in 1992 was the current version. According to this guideline "the Guinea Pig Maximisation Test (GPMT) [...] and the non-adjuvant Buehler Test are given preference over other methods".“

Test material

Test material information

Constituent 1

Reference substance name:

Hexadecyltrimethoxysilane

EC Number:

240-464-3

EC Name:

Hexadecyltrimethoxysilane

Cas Number:

16415-12-6

Molecular formula:

C19H42O3Si

IUPAC Name:

hexadecyl(trimethoxy)silane

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 Netherlands, Netherlands and Harlan Winkelmann GmbH, Germany
- Age at study initiation: 4 - 5 weeks
- Weight at study initiation: 250 - 300 g
- Housing: stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09 Aug 2004 To: 15 Sep 2004

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, semiocclusive

Vehicle:

corn oil

Concentration / amount:

50% in corn oil

Day(s)/duration:

0-17

Adequacy of induction:

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

Challenge

No.:

#1

Route:

epicutaneous, semiocclusive

Vehicle:

corn oil

Concentration / amount:

20% in corn oil

Day(s)/duration:

29

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10 (control group), 20 (test group)

Details on study design:

RANGE FINDING TESTS
Five animals were selected from those available and the flanks clipped free of hair. Each animal was dosed with 2 concentrations of the test substance, 1 on either flank. A gauze patch measuring at least 20x20 mm was soaked with 0.4 ml of the selected concentration of the test substance. This was then placed onto the selected treatment site. When both sites of the animal had been treated, they were secured in position by wrapping the trunk with a length of adhesive strapping. All animals were treated in this manner such that a total of 5 concentrations (100%, 50%, 20%, 10% and 5% in corn oil) of the test substance were each dosed in duplicate. The adhesive strapping and patches were removed after 6 hours contact with the skin. The treated sites were washed with water at approximate body temperature to remove any remaining test substance. Twenty four and 48 hours after removal of the dressings, the treated sites were examined for signs of reaction to treatment.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance in corn oil (0.4 ml)
- Control group: corn oil (0.4 ml)
- Site: left flank
- Frequency of applications: every 7 days (days 8 to 10 and 15 to 17 of the study)
- Duration: Days 0-17
- Concentrations: 50% in corn oil (test group)
- Examination of treated sites: 24 and 48 hours

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (challenge)
- Day of challenge: 29
- Exposure period: 6 h
- Test groups: test substance in corn oil and corn oil only
- Control group: test substance in corn oil and corn oil only
- Site: posterior right flank (test substance) and anterior right flank (corn oil)
- Concentrations: 20%
- Evaluation (hr after challenge): 24 and 48 h after patch removal

Animals used in the main sensitisation assessment were weighed on Day 1 of the study and again on termination of the study following completion of the challenge procedures. All animals were killed following the end of the experimental procedure. No necropsy examination was performed in these animals.

Challenge controls:

The control group is actually a challenge control.

Positive control substance(s):

yes

Remarks:

alpha-Hexylcinnamaldehyde

Results and discussion

Positive control results:

Alpha-Hexylcinnamaldehyde (induction 70% in DMSO and challenge 15% in acetone) was used as positive control in periodic reliability checks. In the most recent reliability check 55% of the guinea pig responded in the test group, whereas none responded in the control group. Thus, the test system is regarded as valid.

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Induction: 0%, challenge: 20%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no clinical signs observed

Remarks on result:

no indication of skin sensitisation

Results 2

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

Induction: 50%, challenge: 20%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no clinical signs observed

Remarks on result:

no indication of skin sensitisation

Results 3

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Induction: 0%, challenge: 20%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no clinical signs observed

Remarks on result:

no indication of skin sensitisation

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

Induction: 50%, challenge: 20%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no clinical signs observed

Remarks on result:

no indication of skin sensitisation

Results 5

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

Any other information on results incl. tables

RANGE FINDING STUDY

A moderate erythema (grade 2) was apparent at sites treated with the undiluted test substance. A slight erythema was observed at sites treated with the test substance at a concentration of 50%. Therefore, a concentration of 50% was selected for use during the induction phases of the main study. A concentration of 20% in corn oil was selected for use at challenge, being judged the highest non-irritant.

 

MAIN STUDY

A slight to moderate erythema (grade 1 and 2) was observed in 20/20 animals of the test group at the first induction, following 6 hours topical exposure to the test substance at 50% concentration. A slight erythema (grade 1) was noted in 2/20 animals of the test group, following the second induction. No reaction was observed in any animal at the third induction. No positive response was observed following administration of the test substance (challenge) at a concentration of 20% in corn oil in either the test or control group 24 and 48 hours following 6 hour topical exposure. No reaction was observed to the vehicle alone.

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:

In a guinea pig skin sensitisation study (Buehler test) conducted to OECD 406 and to GLP the test material did not induce any skin sensitisation in any of the animals tested at any time point. There were no clinical signs of systemic toxicity.