Registration Dossier

Administrative data

Description of key information

In the key experimental non-LLNA skin sensitisation study, a Buehler test conducted with guinea-pigs, 3-(2,3-epoxypropoxy)propyltrimethoxysilane was not sensitising in guinea pigs (Hüls, 1993). Additionally, a good quality study that was conducted using human subjects also evidenced negative results (TKL Research, 2001).

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:
26.09.1993 to 05.11.1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler 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 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.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, 33176 Borchen.
- Age at study initiation: 'young'
- Weight at study initiation: <500 g
- Housing: Maximum of five animals per Makrolon type IV cage.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.3°C
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 26.09.1993 to 05.11.1993
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% test substance.
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% test substance.
No. of animals per dose:
Pre-test: 3
Main study group: 20
Control group: 10
Details on study design:
RANGE FINDING TESTS: 2.5%, 25% and 50% w/w test substance in corn oil MEH 56 and 100% test substance were applied to the skin of three guinea-pigs, under occlusive conditions for six hours. The skin reactions were then assessed 24 and 48 hours after dressing removal. No signs of irritation were observed in any of the animals.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three
- Exposure period: Six hours
- Control group: Treated the same with corn oil MEH 56
- Site: Left flank
- Frequency of applications: On days 0, 7 and 14
- Concentrations: 100% undiluted test substance


B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Day 28
- Exposure period: Six hours
- Test groups: 100 % test substance
- Control group: Corn oil MEH 56
- Site: Right flank
- Evaluation (hr after challenge): 24 and 48 hours after dressing removal.

In a separate study, Dunkin-Hartley guinea-pigs were treated with standard allergen 1-chlor-2,4-dinitrbenzol (0.05-0.1 % in vaseline) under the conditions of the Buehler test. They were tested alongside negative controls (vaseline only). This separate study showed the sensitivity of the Buehler test in the laboratory in question.
Challenge controls:
Negative - corn oil MEH 56
Positive control substance(s):
yes
Remarks:
1-chlor-2,4-dinitrobenzol (CDNB; separate investigation)
Positive control results:
Approximately 40-50% of animals gave a positive result.
Reading:
1st reading
Hours after challenge:
30
Group:
test group
Dose level:
100% test substance
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No effect on body weight gain in control or test animals.
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
54
Group:
test group
Dose level:
100 % test substance
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No effect on body weight gain in control or test animals.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
30
Group:
negative control
Dose level:
100% vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
54
Group:
negative control
Dose level:
100% vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.05% 1-chloro-2,4-dinitrobenzol in vaseline
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
No clinical effect observed
Remarks on result:
positive indication of skin sensitisation
Remarks:
In an assay to determine the sensitivity of the assay, carried out between 1993-04-25 and 1993-05-27, 50% of animals showed evidence of sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
0.05% 1-chloro-2,4-dinitrobenzol in vaseline
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
No clinical effects observed
Remarks on result:
positive indication of skin sensitisation
Remarks:
In an assay to determine the sensitivity of the assay, carried out between 1993-04-25 and 1993-05-27, 50% of animals showed evidence of sensitisation

There were no substance related effects or influence on body weight in either test or control animals. There was no
erythema or edema observed during Induction Phase I, II or III; no skin irritation was observed in the control animals.
There was no skin irritation observed in either test or control animals in the Challenge Phase.

Interpretation of results:
GHS criteria not met
Conclusions:
In a well conducted Buehler test (reliability score 1) conducted to OECD 406 and GLP, DYNASYLAN GLYMO (glycidyloxypropyl-trimethoxysilan) was not a skin sensitiser in guinea-pigs.
Executive summary:

In a well conducted Buehler test (reliability score 1) conducted to OECD 406 and GLP, DYNASYLAN GLYMO (glycidyloxypropyl-trimethoxysilan) was not a skin sensitiser in guinea-pigs.

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

The key study for skin sensitisation was conducted according to an OECD Test Guideline 406, and in compliance with GLP. The dose level selected in the range finding test, for the main study and challenge exposure, was 100% undiluted test substance. There was no substance related clinical effects in any of the test or control animals. Furthermore, no erythema or oedema during induction or challenge phase occurred. The positive and negative control animals gave expected responses. The substance was concluded to be not sensitising to Guinea pig skin in a well conducted Buehler test (Hüls, 1993).

A supporting repeated insult patch test with 3-(2,3-epoxypropoxy)propyltrimethoxysilane is also included in the data set. The objective of the study was to determine the ability of the test material to cause sensitisation by repeated applications to the skin of selected human subjects. A semiocclusive application of 1% of the test material to 111 subjects over a 6 week period comprising of an induction, rest and challenge phase was carried out. The subjects were between 20 and 75 years old with a mean age of 47.9 years and mainly of Caucasian origin. One-hundred subjects completed the study. There were no dermal reactions noted during induction or challenge with the test article. Under the conditions of this study, there was no evidence of sensitisation to the test article (TKL Research, 2001).

A supporting guinea pig maximisation tests (GPMT) which was conducted according to OECD Test Guideline 406, with acceptable restrictions, concluded that the test material is not sensitising to skin (Dow Corning Corporation, 1984).

In a Buehler test which was not conducted according to any guideline and not in compliance with GLP showed the test material to be a very slight sensitiser in guinea pigs (Dow Corning Corporation, 1982).

In a Buehler test which was conducted according to a test protocol comparable to OECD Test Guideline 406 and in compliance with GLP, the substance was reported to be a very slight sensitiser, although, this is considered to be ambiguous (FDRL, 1982).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data do not suggest that 3-(2,3-epoxypropoxy)propyltrimethoxysilane should be classified as a skin or respiratory sensitiser according to Regulation (EC) No. 1272/2008.