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Description of key information

The key skin sensitisation study, conducted according to OECD Test Guideline 406 and in compliance with GLP, concluded the registered substance, N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine (CAS No. 3069-29-2, EC No. 221-336-6), to be a skin sensitiser (Safepharm Laboratories Ltd, 1988). 19/20 test animals showed positive responses at both 24 and 48-hour readings.

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:
08/01/1988-12/02/1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (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.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Interfauna (UK) Ltd., Wyton, Huntingdon, Cambridgeshire
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 315-395 g
- Housing:The animals were housed in groups of up to 4 in solid-floor polypropylene cages furnished with softwood shavings.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-23
- Humidity (%): 35-60
- Air changes (per hr): ca.15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
water
Concentration / amount:
INDUCTION: First exposure: a row of three injections (0.1 ml each), Freunds Complete Adjuvant plus distilled water in the ratio of 1:1, 0.1% (w/v) dilution of test material in distilled water, 0.1% (w/v) dilution of test material in a 1:1 preparation of Freud's Complete Adjuvant plus distilled water. Second exposure: undiluted test material.
CHALLENGE: undiluted
































































































Intradermal induction: 0.1% (w/v) in distilled water
Topical induction: undiluted as supplied
Topical challenge: undiluted as supplied
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
INDUCTION: First exposure: a row of three injections (0.1 ml each), Freunds Complete Adjuvant plus distilled water in the ratio of 1:1, 0.1% (w/v) dilution of test material in distilled water, 0.1% (w/v) dilution of test material in a 1:1 preparation of Freud's Complete Adjuvant plus distilled water. Second exposure: undiluted test material.
CHALLENGE: undiluted
































































































Intradermal induction: 0.1% (w/v) in distilled water
Topical induction: undiluted as supplied
Topical challenge: undiluted as supplied
No. of animals per dose:
20 (test), 10 (control) animals
Details on study design:
RANGE FINDING TESTS: The dose level for each of the three stages of the main study were determined using one or two guinea pigs and up to four dose levels tested on each animal.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Test groups: First exposure: a row of three injections (0.1ml each), Freunds Complete Adjuvant plus distilled water in the ratio of 1:1, 0.1% (w/v) dilution of test material in distilled water, 0.1% (w/v) dilution of test material in a 1:1 preparation of Freud's Complete Adjuvant plus distilled water. Second exposure: undiluted test material.
- Control group: identical to test group but without test material
- Site: shoulder region of each animal
- Exposure period: one week, followed by a 48-hour occlusive exposure.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2
- Site: right flank
- Concentrations: undiluted
- Evaluation (hr after challenge): 24 and 48 hours

Positive control substance(s):
yes
Remarks:
Formaldehyde (40% aqueous solution)
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
undiluted
No. with + reactions:
19
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
undiluted
No. with + reactions:
19
Total no. in group:
20
Clinical observations:
desquamation and thickening of skin
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
20% v/v
No. with + reactions:
17
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
20% v/v
No. with + reactions:
17
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
The test material is reported to be an extreme sensitiser to guinea pig skin in a study conducted according to OECD Test Guideline 406 and in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The key skin sensitisation study is the only available study for this endpoint. The study was conducted according to OECD Test Guideline 406 and in compliance with GLP.

Twenty test and ten control animals were used for the main study. Following sighting studies, the following concentrations were used in the induction and challenge phases:

Intradermal Induction: 0.1% (w/w) in distilled water

Topical Induction: undiluted as supplied

Topical Challenge: undiluted as supplied

The test material produced a 95 % (19/20) sensitisation rate and was concluded to be sensitising to guinea pig skin.

A supporting skin sensitisation test for the analogue substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS No. 1760-24-3, EC No. 217-164-6) is included only to support the read-across justification for the genetic toxicity endpoint currently using this analogue substance.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available information, N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine is classified for skin sensitisation Category 1A, H317: "May cause an allergic skin reaction" according to Regulation (EC) No. 1272/2008.

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