Registration Dossier

Administrative data

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:
experimental study
Adequacy of study:
key study
Study period:
July 03rd 1989, August 03rd 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD guideline and GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Animal strain as given in the report: Pirbright White Strain (Tif: DHP)
- Source: CIBA-GEIGY Limited, Tierfarm, 4332 Stein / Switzerland
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: 336 to 446 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: standard guinea pig pellets - NAFAG No. 845, Gossau SG, ad libitum
- Water: fresh water, ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+3°C
- Humidity (%): 30 to 70 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light cycle day

All batches of the diet are assayed for nutritive ingredients and contamination level by the manufacturer. Analytical results are available at the animal supply office. The drinking water is examined periodically by the IWB (Industrielle Werke Basel).
Route:
intradermal and epicutaneous
Vehicle:
petrolatum
Concentration / amount:
The following concentrations have been examined on separate animals for the evaluation of the primary irritant potential and the maximum subirritant concentration: 30 and 10 % in vaseline. Erythema reactions were observed with 30% in vaseline. 30% was, therefore, selected for the epidermal induction application and 10% as maximum subirritant concentration for the epidermal challenge application.
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
The following concentrations have been examined on separate animals for the evaluation of the primary irritant potential and the maximum subirritant concentration: 30 and 10 % in vaseline. Erythema reactions were observed with 30% in vaseline. 30% was, therefore, selected for the epidermal induction application and 10% as maximum subirritant concentration for the epidermal challenge application.
No. of animals per dose:
10 male and 10 female guinea pigs per group
Details on study design:
The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later.
First Induction, intradermal application
Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shaved neck of the guinea pigs as follows:
- adjuvant/saline mixture 1:1 (v/v)
- test article in sesame oil (w/v)
- test article in the adjuvant saline mixture (w/v)
Second Induction, epidermal application
One week later the test article was incorporated in vaseline (w/w) and applied on a filterpaper patch to the neck of the animals (patch 2x4 cm; approx. 0.4 g paste per patch; occluded administration for 48 hours).

Challenge
Two weeks after the epidermal induction application the animals were tested on the flank with test material in vaseline (w/w) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration for 24 hours).

Twenty four hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale. A second evaluation was made 48 hours after removing the dressings. The sensitising potential of the test item was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the test.

Observations and records
Induction reactions
After the intradermal and the epidermal induction application irritant reactions are normally induced by the adjuvant, the high test article concentration, or the sodium lauryl sulfate pretreatment. Because most of the reactions are treatment related and not compound related, the reactions are only described in special cases in the section of results.
Challenge reactions
Twenty four hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale. A second evaluation was made 48 hours after removing the dressings.

The sensitising potential of the test item was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the test.
Challenge controls:
A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test article (at least 10 animals) to check the maximum subirritant concentration of the test article in adjuvant treated animals.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
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: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
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.
Interpretation of results:
not sensitising
Remarks:
Migrated information (EU 67/548/EEC and EC/1271/2008)
Conclusions:
In the GPMT, none of the guinea pigs of the test group showed skin reactions 24 and 48 hours after challenge with 10% test item.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The assessment of skin sensitization was performed by two guinea pig maximization studies (Ciba-Geigy, 1987 and Ciba-Geigy, 1989). Both studies were performed following OECD testing guideline 406 and under GLP. In the key study, 10% were used as the highest concentration for challenge whereas for the supporting study, 3% was used. In both cases, none of the 20 animals in the test group showed skin reactions.

In the key study, the following concentrations were examined on separate animals for the evaluation of the primary irritant potential and the maximum subirritant concentration: 30 and 10 % in vaseline. Erythema reactions were observed with 30% in vaseline. 30% was, therefore, selected for the epidermal induction application and 10% as maximum subirritant concentration for the epidermal challenge application.


Migrated from Short description of key information:
The substance did not cause skin sensitization in the guinea pig maximization test (OECD 406, GLP).

Justification for selection of skin sensitisation endpoint:
GLP-compliant guideline study

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Migrated from Short description of key information:
No experimental data is available regarding respiratory sensitization. As the substance is a viscous liquid of low volatility, inhalation route of exposure is not considered relevant.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for skin sensitization under Directive 67/548/EEC.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008.