N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]ethylenediamine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The test was performed in 1992 when the OECD Guideline 406 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:

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%

Day(s)/duration:

48 hours

Challenge

Route:

epicutaneous, occlusive

Vehicle:

other: sterile Codex liquid paraffin

Concentration / amount:

10%

Day(s)/duration:

48 hours

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 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:

The control group is actually a challenge control.

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

intradermal induction 0.1 % (v/v); challenge 10% (v/v)

No. with + reactions:

6

Total no. in group:

20

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

intradermal induction 0%; challenge 10% (v/v)

No. with + reactions:

0

Total no. in group:

20

Results 3

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

intradermal induction 0.1 % (v/v); challenge 10% (v/v)

No. with + reactions:

6

Total no. in group:

20

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

intradermal induction 0%; challenge 10% (v/v)

No. with + reactions:

0

Total no. in group:

20

Results 5

Group:

positive control

Remarks on result:

not measured/tested

Remarks:

not reported

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:

other: CLP/EU GHS Category 1A (H317) according to Regulation (EC) No 1272/2008

Conclusions:

In a guinea pig maximisation study conducted to OECD 406 and to GLP the source substance 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.