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Administrative data

Description of key information

The key study is the only study available for skin sensitisation. It was carried out in accordance with an appropriate OECD test guideline (OECD 406) and in compliance with GLP and found 3-(trimethoxysilyl)propylamine to be not sensitising

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:
11/10/2000 to 10/11/2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
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 Guinea Pig Maximisation test method.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: Charles Rivers Laboratories, Raleigh, NC

- Age at study initiation: Young adult

- Weight at study initiation: 280 - 336 g (males) and 285 - 319 g (females)

- Housing: Individual suspended wire-mesh cages.

- Diet: PMI Nutritional International Certified Guinea Pig LabDiet 5026, ad libitum

- Water: Municipal water ad libitum

- Acclimation period: Minimum 7 days.

ENVIRONMENTAL CONDITIONS

- Temperature: 68-74 °F (20-23.3 °C)

- Humidity (%): 30-62%

- Air changes (per hr): Not stated

- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 11/10/2000 To: 10/11/2000
Route:
intradermal and epicutaneous
Vehicle:
other: Mineral oil
Concentration / amount:
Intradermal induction: 5%
Topical induction: 100%
Topical challenge: 10%
Route:
epicutaneous, occlusive
Vehicle:
other: Mineral oil
Concentration / amount:
Intradermal induction: 5%
Topical induction: 100%
Topical challenge: 10%
No. of animals per dose:
Test group: 10 male and 10 female
Control group: 5 male and 5 female
Details on study design:
RANGE FINDING TESTS:

The test article was prepared in mineral oil and 1:1 Freund's Complete Adjuvant and sterile saline mix at concentrations of 1, 3 and 5% (w/v) for intradermal injection. The test article was also prepared at concentrations of 2.5, 5. 10. 25 and 50% in mineral oil for topical application.

Intradermal: Four animals received 0.1 ml intradermal injections on the dorsal surface. Three pairs of injections were made along the spine of each guinea pig. Each animal received one injection of 1, 3 and 5% test article in mineral oil and in 1:1 Freund's Complete Adjuvant and sterile saline mix.

Topical: 0.3 ml per site were applied under four patches of Whatman No 5 filter paper. The patches were secured with micropore tape, occluded with plastic wrap and overwrapped with non-irritating elastic tape. There were three sites per guinea pig and four sites per concentration. The various concentrations of test article were rotated around the available sites to minimise site-to-site variations in response. The period of exposure was 24 hours, after which the patches were removed and the sites washed with disposable paper towels moistened with tepid tap water.

MAIN STUDY:

A. INTRADERMAL INDUCTION EXPOSURE

- No. of exposures: 1

- Exposure period: N/A

- Test groups: 5% (w/v) in mineral oil and 5% (w/v) in 1:1 Freund's Complete Adjuvant (FCA) and sterile saline mix.

- Control group: Negative control: Mineral oil and a 50% mix of mineral oil and 1:1 FCA/saline; Positive control: 5% w/v HCA in 0.5% methoxycellulose/0.1% Tween 80 and 5% (w/v) HCA in 1:1 FCA/saline.

- Site: Two rows of three injections on dorsal midline (0.1 ml)

- Frequency of applications: N/A

- Duration: N/A

- Concentrations: 5%

B. TOPICAL INDUCTION EXPOSURE

- No. of exposures: 1

- Exposure period: Day 0

- Test groups: 100% undiluted test article

- Control group: Negative control: Deionised water; Positive control: 50% HCA in acetone

- Site: Over injection sites

- Frequency of applications: N/A

- Duration: 48 hours

- Concentrations: Neat

C. CHALLENGE EXPOSURE

- No. of exposures: 1

- Day(s) of challenge: Day 21

- Duration: 24 hours

- Test groups: 10% in mineral oil

- Control group: Negative control: 10% test article in mineral oil; Positive control: 10% HCA in acetone

- Site: Anterior left flank

- Concentrations:

- Evaluation (hr after challenge):

OTHER:
Challenge controls:
None
Positive control substance(s):
yes
Remarks:
Alpha-hexylcinnamaldehyde (HCA)
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
15
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 15.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Vehicle only
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Vehicle only. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Vehicle only
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Vehicle only. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Vehicle only
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Vehicle only. No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Vehicle only
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Vehicle only. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 5%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Vehicle only
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: Vehicle only. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
5%
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 5%. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Vehicle only
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: Vehicle only. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

Mortality:

There were no deaths during the study.

Clinical Observations:

There were no clinical findings noted during the study.

Body weights:

There were no remarkable body weight changes observed during the study.

Dermal observations:

Primary Irritation Phase: Intradermal injections of 5% concentrations of the test article in mineral oil and 1:1 FCA:saline did not cause ulceration of the injection sites and were systemically well-tolerated. Therefore, the 5% concentration was considered appropriate for intradermal induction in the main study.

During the topical range-finding portion of the Primary Irritation Phase, undiluted test article caused minimal dermal irritation and was therefore chosen for the topical induction. As the maximal non-irritation concentration, 10% test article in mineral oil was chosen for challenge dosing.

Challenge Phase: The test group was noted with 15 slight (grade 1) dermal responses for the test article-treated sites and four slight dermal responses for the vehicle-treated sites at the 24-hour observations. All dermal irritation had completely subsided by the 48 -hour observation.

The negative control group was noted with six slight dermal responses for the test article-treated sites and four slight dermal responses for the vehicle-treated sites at the 24-hour observation. All dermal irritation for both sites had completely subsided by the 48-hour observation.

The positive control group animals were noted with nine slight and one moderate (grade 2) dermal reactions at the 24-hour observation and six slight dermal reactions at the 48-hour observation. No dermal irritation was noted on the vehicle-treated sites.

Incidence and Severity Indices:

The Incidence Index for the positive control was 10/10 (100%) following challenge dosing with 10% HCA. The Severity Index was 1.1 and 0.6 at the 24- and 48-hour observations, respectively.

The Incidence Index for the test group was 0/20 (0%) following challenge dosing with 10% Silquest A-1110 Silane. The Severity Index was 0.8 and 0.0 at the 24- and 48 -hour observations, respectively, for the test group and 0.6 and 0.0 at the 24- and 48 -hour observations, respectively, for the negative control group.

Interpretation of results:
GHS criteria not met
Conclusions:
In a study conducted according to OECD 406 and in compliance with GLP, 3-(trimethoxysilyl)propylamine was not sensitising in the guinea pig.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In the key skin sensitisation study (WIL, 2001), 3-(trimethoxysilyl)propylamine was found to be not sensitising in a test conducted according to OECD 406 (guinea pig maximisation test) and in compliance with GLP.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

On the basis of the available data 3-(trimethoxysilyl)propylamine does not require classification as a skin sensitiser according to EU Directive 67/548/EEC and Regulation (EC) 1272/2008. There are no data to suggest that the substance is a respiratory sensitiser.