Registration Dossier

Administrative data

Description of key information

Guinea Pig Maximisation Test (GPMT): not sensitising (GLP, OECD 406; 1990)

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted in 1991, when the GPMT was the internationally accepted and recommended study type in order to assess sensitizing potential of a substance.
Species:
guinea pig
Strain:
other: Pirbright White Strain
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Tierfarm, Stein / Switzerland
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: 322 to 449 g
- Housing: individually
- Diet (e.g. ad libitum): guinea pig pellets (NAFAG No. 84 5, Gossau SG) ad libitum
- Water (e.g. ad libitum): fresh water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours
Route:
intradermal
Vehicle:
other: sesame oil
Concentration / amount:
5 %
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
30 %
Day(s)/duration:
48h
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
10 %
No. of animals per dose:
Number of animals in test group: 20
Number of animals in negative control group: 20
Details on study design:
RANGE FINDING TESTS:
The following concentrations have been examined on separate animals for the evaluation of the primary irritant potential and the maximum subirritant concentration of the test article:
30 and 10 % in vaseline. The tested concentrations did not induce erythema reactions. 30 % was, therefore, selected for the epidermal induction application.
10 % was used as subirritant concentration for the challenge application, because highest concentrations may lead to nonspecific reactions in adjuvant treated animals (Magnusson B., Contact Dermatitis 6, 46-50, 1980).
The concentration for the intradermal injections was selected on account of the solubility of the test article in standard vehicles. Concentration: 5 %
Vehicle: sesame oil.

MAIN STUDY
A. INDUCTION EXPOSURE
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).
The application sites were pretreated the day before with 10 % sodium lauryl sulfate (open application).

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

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):
yes
Remarks:
2,4-dinitrochlorobenzene, paraphenylene- diamine or potassium-dichromate
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The potential of the test substance to induce delayed contact hypersensitivity was assessed using the Guinea Pig Maximisation Test (GPMT) in a GLP conform study according to OECD guideline 406 (1990). Groups of 10 male and 10 female Pirbright White Strain guinea pigs were treated with 5 and 30 % w/w of the test substance in sesame oil or vaseline or with the vehicle alone in the induction phase. The tested concentrations did not induce erythema reactions. 10 % was used as subirritant concentration for the challenge application, because higher concentrations may lead to nonspecific reactions in adjuvant treated animals. 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 substance was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the testand increased throughout the study period. There is no incidence of positive animals per group and individual challenge reactions. Under the experimental conditions employed, none of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings. The test substance is, therefore, not classified as a sensitizer in guinea pigs according to the grading of Magnusson and Kligman.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

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