Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
16.09.1991 to 19.10.1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
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. 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.

Test material

Constituent 1
Chemical structure
Reference substance name:
N-(3-(trimethoxysilyl)propyl)ethylenediamine
EC Number:
217-164-6
EC Name:
N-(3-(trimethoxysilyl)propyl)ethylenediamine
Cas Number:
1760-24-3
Molecular formula:
C8H22N2O3Si
IUPAC Name:
N-(3-(trimethoxysilyl)propyl)ethylenediamine

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: young adult
- Weight at study initiation: 300-500 g
- Housing: by sex and in groups of up to 5 or 6 (2 for the preliminary studies), in polystyrene cages with perforated flooring
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
other: sterile Codex liquid paraffin
Concentration / amount:
Intradermal injections: 0.1%
Epicutaneous induction: 10%
Topical challenge: 10%
Challenge
Route:
epicutaneous, occlusive
Vehicle:
other: sterile Codex liquid paraffin
Concentration / amount:
Intradermal injections: 0.1%
Epicutaneous induction: 10%
Topical challenge: 10%
No. of animals per dose:
Control: 20
Test: 20
Details on study design:
Induction
Treated group:
By intradermal route: 3 series of 2 x 0.1 ml injections.
1) FCA at 50% (v/v) in an isotonic injectable solution;
2) test substance in a 0.1% (v/v) solution in sterile Codex liquid paraffin;
3) mixture 50/50 (v/v): test substance in a 0.2% (v/v) in sterile Codex liquid paraffin + FCA at 50% (v/v) in an isotonic injectable solution, i.e. a final 0.1% concentration of the test substance.

By topical occlusive route for 48 hours: with 0.5 ml of the test substance in a 10% (v/v) solution in sterile Codex liquid paraffin. As this application only provoked a weak irritation during the preliminary study, a skin painting was performed on Day 8, with 0.5 ml of sodium lauryl sulfate at 10% (w/w) in Codex paraffin.

Control: The intradermal injections and the topical occlusive application for 48 hours were carried out under the same conditions as in the treated group, sterile sterile Codex liquid paraffin replacing the test substance.

The rest period was 11 days without treatment.

Challenge
Topical occlusive application for 24 hours performed in the treated and control groups with the test substance in a 10% (v/v) solution in
sterile Codex liquid paraffin and at a rate of 0.5 ml. The vehicle was also applied during the challenge.

The cutaneous macroscopic examinations were performed according to Magnusson & Kligman scale and to the challenge application site, 24 and 48 hours after removal of the patches. Histopathological examinations of the skin were performed for nine animals of the treated group that showed doubtful macroscopic reactions at 24 hours and for one animal of the control group, which showed abnormal macroscopic reactions at 24 hours.
Challenge controls:
Vehicle or water + test article
Positive control substance(s):
yes

Results and discussion

Positive control results:
In total, 6 substances were used as positive controls: dihydrocoumarin in solution at 20% (v/v) in ethanol for the induction and the challenge respectively; paraphenylenediamine in solution at 10 and 0.5 % (w/w) in deionised water for induction and challenge respectively; formalin in solution at 5% (w/w) in deionised water for induction and challenge respectively; penicillin G in suspension at 25 and 10% (w/w) in ethanol for induction and challenge respectively; benzocaine (Ethoform) in suspension at 25% (w/w) in absolute ethanol for induction and 10% (w/w) in sterile codex liquid paraffin for challenge.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10% v/v
No. with + reactions:
6
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10% v/v
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10% v/v
No. with + reactions:
6
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
10% v/v
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Dihydrocoumarin in solution at 20% (v/v)
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Dihydrocoumarin in solution at 20% (v/v)
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Paraphenylenediamine in solution at 10%
No. with + reactions:
11
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
paraphenylenediamine in solution at 0.5% (w/w) in deionised water
No. with + reactions:
11
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
formalin in dilution at 5% (w/w) in deionised water
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
formalin in dilution at 5% (w/w) in deionised water
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
penicillin G in suspension at 25% (w/w) in ethanol at 70°C
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
penicillin G in suspension at 10% (w/w) in ethanol at 70°C
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Benzocaine in suspension at 25% (w/w) in absolute ethanol
No. with + reactions:
9
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Benzocaine in suspension at 10% (w/w) in sterile Codex liquid paraffin
No. with + reactions:
9
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
propylene glycol
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
propylene glycol
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

Signs of irritation were noted during the induction.

The macroscopic and histopathological examinations revealed pathological lesions of delayed hypersensitivity in 6 out of the 20 treated animals. A weak irritation was noted in one animal of the control group. No other cutaneous abnormality was noted in the 19 other guinea pigs examined in the control group.

Overall, the test substance provoked a reaction of cutaneous sensitisation in 30% of the animals examined.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
In a guinea pig maximisation study conducted according to OECD 406 and in compliance with GLP (reliability score 1) N-(3-(trimethoxysilyl)propyl)ethylenediamine provoked a positive reaction in 30% of the test animals. Hence, this test substance is considered to be a skin sensitiser.