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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study. According to ECHA guidance, a study with a read-across substance can have no reliability of higher than 2. The study itself is valid without restriction.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(adopted May 12, 1981)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
other: Pirbright White Strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba Geigy Ltd. Tierfarm, Sisseln, Switzerland
- Age at study initiation: no data
- Mean weight at study initiation: males = 382.7 g; females = 376.1 g
- Housing: housed individually in Macrolon cages (Type 3)
- Diet: ad libitum; standard guinea pig pellets -NAFAG No.847, Gossau SG (assayed for nutritive ingredients and contamination level by the manufacturer)
- Water: ad libitum (drinking water was examined periodically by the IWB (Industrielle Werke Basel)
- Acclimation period: 8 days
- Rationale for choice: The albino guinea pig is the recommended species for skin sensitization studies.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: Sesame oil (Intradermal induction), Vaseline (epicutaneous induction and challenge)
Concentration / amount:
Intradermal induction: 1%
epicutaneous induction: 30%
challenge: 3%
Route:
epicutaneous, occlusive
Vehicle:
other: Sesame oil (Intradermal induction), Vaseline (epicutaneous induction and challenge)
Concentration / amount:
Intradermal induction: 1%
epicutaneous induction: 30%
challenge: 3%
No. of animals per dose:
Test group : 20 animals
control group: 20 animals
Details on study design:
RANGE FINDING TESTS:
Separate animals were treated with the test article for the evaluation of the primary irritation threshold concentration. 10 % in Vaseline induced erythema reactions. 3 % in Vaseline did not induce skin reactions and, therefore, this concentration was used as the maximal sub-irritant concentration for the challenge applications.

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal Injection
- Site/Area: Neck region/2 x 4 cm
- No. of injections/animal: 3 pairs
- Test substance group (cranial; 2 injections side by side): Freund's complete adjuvant (FCA) blended (1:1, v/v) with physiol. saline
- Test substance group (middle; 2 injections side by side): The test article (1%) in sesame oli
- Test substance group (caudal; 2 injections side by side): Freund's complete adjuvant blended (1:1, v/v) with physiol. saline + 1 % test article in vehicle.
- Control group (cranial; 2 injections side by side): Freund's complete adjuvant (FCA) blended (1:1, v/v) with physiol. saline
- Control group (middle; 2 injections side by side): Sesame oil
- Control group (caudal; 2 injections side by side): Freund's complete adjuvant blended (1:1, v/v) with physiol. saline + 1 % test article in vehicle.
- Volume per injection: 0.1 ml
- Evaluation (hr after injection): from 24 hour till day 7
- Exposure period: Single exposure

Epicutaneous induction exposure
- Time schedule: 1 week after intradermal injection
- Site: same site as intradermal injections
- Frequency of applications: Once.
- Area of application: 2 x 4 cm (filterpaper patch)
- Concentrations: 30% (test group), vehicle (control group)
- Amount applied: approx. 0.4 g paste of test substance in vaseline
- Type of coverage: occlusive
- Duration: 48 hours
- Evaluation (hr after challenge): directly after removal of patch

B. CHALLENGE EXPOSURE (all animals i.e treated animals and control animals)
- Time schedule: 2 weeks after termination of epicutaneous induction exposure
- Site: flank
- Area of application: 2 x 2 cm (filterpaper patch)
- Concentrations: 3%
- Amount applied: 0.2 g paste of test substance in vaseline (one flank) and vaseline (other flank)
- Type of coverage: occlusive
- Duration: 24 hours
- Evaluation (hr after challenge): 24 and 48 hours after termination of exposure

B.2. RECHALLENGE EXPOSURE
After the standard challenge exposures, 6 animals of the test group showed very slight skin reactions 24 and 48 hours. Because all the reactions observed were mild, a second challenge application was performed after a further period of 1 week.

SCORING SYSTEM: Draize in Appraisal of the Safety of chemicals in Foods, Drugs and Cosmetics (1959), The US Association of Food and Drug Officials (AFDO).
Erythema and eschar formation:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Oedema formation:
No oedema: 0
Very slight edema (barely perceptible): 1
Slight edema (edges of area well defined by definite raising): 2
Moderate oedema (raised approximately 1 millimetre): 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4
Positive control substance(s):
yes
Remarks:
The sensitivity of the assay was checked every six months with Paraphenylene-diamine or Potassium-dichromate
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
3%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 3%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
3%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 3%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
3%
No. with + reactions:
7
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 3%. No with. + reactions: 7.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
3%
No. with + reactions:
6
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 3%. No with. + reactions: 6.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
3%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 3%. No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
3%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 3%. No with. + reactions: 1.0. Total no. in groups: 20.0.

Average body weights at termination

- males = 656 g

- females = 526.1 g

Interpretation of results:
not sensitising
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:
Justification for selection of skin sensitisation endpoint:
The substance is considered to be non-sensiting to skin based on the minimal erythematous response (1/20 responders) observed at re-challenge in a guinea-pig M&K study with its close analogue.

Justification for classification or non-classification

Not classified for skin sensitisation, according to the criteria of CLP regulation EC No.1272/2008