Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Skin sensitisation (OECD 406), Buehler test: not sensitising (RA from CAS 16415-12-6)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across source
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
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
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
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
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
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 with OECD 406 and under GLP the source substance did not induce any skin sensitisation in any of the animals tested at any time point. There were no clinical signs of systemic toxicity. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in sensitisation potential.
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
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".“
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
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
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
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.
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
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
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
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
Group:
positive control
Remarks on result:
positive indication of skin sensitisation

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.

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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No data on skin sensitisation of trimethoxyoctadecylsilane (CAS 3069-42-9) are available. Therefore, the risk assessment was performed based on the available data from the source substance hexadecyltrimethoxysilane (CAS 16415-12-6). In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and following the Read across assessment framework (RAAF, ECHA 2017) read across from an analogue substance has been applied to support the human health hazard assessment of trimethoxyoctadecylsilane (CAS 3069-42-9).

 

Skin sensitisation

The skin sensitising properties of Hexadecyltrimethoxysilane (CAS 16415-12-6) were tested in a study performed according to OECD 406 under GLP conditions using the test for delayed contact hypersensitivity in guinea pigs (Buehler test, Research Toxicology Centre SpA, 2004).The Buehler test was performed on 30 female Dunkin Hartley guinea pigs. For the dermal inductions the initially test item concentration was 50% (v/v). A 20% (v/v) preparation of the test item was selected for the challenge application. Topical application of the appropriate test substance concentrations (20 test animals) or vehicle (10 control animals) was performed once a week at the flanks of each animal for three consecutive weeks. Seven days after the last topical application of the test substance or vehicle all animals were challenged with the test substance at a concentration of 20% (v/v). Skin reactions of all animals were evaluated 24 and 48 hours after challenge administration. A slight to moderate erythema (grade 1 and 2) was observed in 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 of the 20 animals of the test group, following the second induction. No reaction was observed at any animal after the third induction. After the challenge application (20% (v/v)) no skin reactions were observed in either the test or the control group 24 and 48 hours following 6 hours topical exposure. Periodically performed validity checks in the test strain with alpha-hexyl cinnamaldehyde gave the respective results.Thus, Hexadecyltrimethoxysilane (CAS 16415-12-6) was not skin sensitising under the conditions of this Buehler test. The same skin sensitising potential is assumed for Trimethoxyoctadecyldilane (CAS 3069 -42 -9).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

Reliable data from a structural analogue on skin sensitisation indicates that the registered substance does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and the available data are therefore conclusive but not sufficient for classification.