Registration Dossier

Administrative data

Description of key information

No skin sensitisation potential of the test substance was observed in a guinea pig maximization study and in a Maurer Optimization Test.

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:
13 Dec 1988 - 12 Jan 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(adopted 1992)
Deviations:
no
GLP compliance:
yes
Remarks:
Dermatotoxicology, CIBA-GEIGY Limited, 4002 Basel / Switzerland
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Two valid in vivo studies performed with guinea pigs are available. No further LLNA study is required.
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 Limited, Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: about 10 weeks old
- Weight at study initiation: 340 - 424 g
- Housing: single housing in Makrolon cages (type 3)
- Diet: standard guinea pig pellets (NAFAG No. 846, Gossau SG), ad libitum
- Water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 30-70
- Photoperiod: 12 hours light cycle
Route:
intradermal
Vehicle:
other: Sesame oil
Concentration / amount:
1%
Route:
epicutaneous, occlusive
Vehicle:
other: Vaseline
Concentration / amount:
30%
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Vaseline
Concentration / amount:
10%
No. of animals per dose:
10 males and 10 females
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 test substance: 10 and 30 % of test substance 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, 1980).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
First induction
Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shaved neck of the guinea pigs as follows:
- adjuvant and saline (1:1)
- test article in sesame oil
- test article in the adjuvant saline mixture
Second induction
-epicutaneous: test substance (30% in vaseline; 0.4 g paste per patch)
- Control group: A control group was treated with adjuvant and the vehicle during the induction period.
- Site: shaved neck
- Frequency of applications: day 1 (first induction) and day 7 (second induction)
- Duration: day 1-7
- Concentrations: intradermal 1%; epicutaneous 30%

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (epicutaneous)
- Day of challenge: 22
- Exposure period: 24 h
- Test groups: vehicle control and test substance (20 animals)
- Control group: vehicle control (20 animals) and test substance (10 animals)
- Site: flank
- Concentrations: 10% in vaseline (0.2 g paste per patch)
- Evaluation (hr after challenge): 24 and 48 hours
The application sites were pretreated the day before with 10 % sodium lauryl sulfate (open application).

OTHER:
One day before the second induction the application sites were pretreated with 10 % sodium lauryl sulfate (open application).
Challenge controls:
Control animals were exposed to vaseline and 10% test substance in vaseline at the epicutaneous challenge.
Positive control results:
No positive control was used in this test. Sensitivity of the strain is checked every 6 months with p-phenylenediamine or potassium dichromate.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
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:
10
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:
negative control
Dose level:
0%
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:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions employed, 0% of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings. Thus, the test substance had no skin-sensitizing potential in albino guinea pigs.
Executive summary:

In a GLP-compliant guinea pig maximization test according to OECD guideline No. 406, 10 male and 10 female animals were first induced and then challenged with the test article to investigate its sensitization potential. Induction was a two-stage operation: First, three pairs of intradermal injections (1 % test substance in sesame oil) were made into the neck of the animals with a 1:1 mixture (v/v) of FCA/ physiological saline, the test substance in sesame oil, and the test substance in a 1:1 mixture (v/v) of FCA/ physiological saline. One week later, 0.4 g of the test article in vaseline at a concentration of 30% was spread onto a filter paper patch (2 x 4 cm) and applied occlusively to the neck of the animals for 48 hours. The application sites were pretreated the day before with 10% sodium lauryl sulfate (open application). Two weeks after the epidermal induction application the animals were tested on the flank with 10% test substance (0.2 g) in vaseline and the vehicle alone for 24 hours. Twenty four hours after removing the dressings the challenge reactions were graded according the Draize scoring scale. An additional evaluation was made 48 hours after removing the dressings. A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period the control animals were treated with the vehicle as well as with the test compound to control the maximum subirritant concentration. No animal of the test group was sensitized by the test substance; all skin reactions at any time point were scored 0. Therefore, under the experimental conditions of this study, the test material is non-sensitizing when topically applied to albino guinea pigs.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The test substance was investigated for its sensitizing potential in a GLP-compliant Maximization test according to OECD guideline 406 (Ciba-Geigy, 1989). Twenty guinea pigs received intradermal induction treatments with 1% in sesame oil and one epicutaneous induction treatment with 30% in vaseline. For intradermal induction, three pairs of injections (adjuvant/saline; test item in vehicle; test item in adjuvant/saline) were given. Epidermal challenge was performed by occlusive application for 24 h two weeks later (10 % in vaseline). Concurrent vehicle control animals were treated similarly, except that during the induction phase the test substance was omitted. No skin reactions were observed either for control or test group animals and therefore no animal was sensitized by the test article under the experimental conditions employed. The sensitivity of the strain is controlled every six months. In conclusion, the test substance is not considered to be a skin sensitizer in albino guinea pigs and does not require classification.

In a supporting study 10 male and 10 female guinea pigs per group were tested on the skin sensitisation potential of the test article following the Maurer Optimization protocol as laid out in the OECD TG 406 adopted in 1981 (Ciba-Geigy, 1983). In this test 10 intradermal inductions (0.1%) followed by an intradermal (0.1%) and epicutaneous (30%) challenges were performed. The vehicle control alone unexpectedly induced a high number of positive reactions (16/20) after intradermal challenge, which was also seen in the test group (16/20). In addition, significant differences between the test group and the vehicle-treated controls were seen after intradermal challenge application, i.e. when the skin barrier was intentionally by-passed. No difference between the test and the control group was seen after epidermal challenge application. The negative results upon epidermal challenge demonstrate that, in artificially sensitized guinea-pigs, exposure of the intact skin to the test compound does not provoke contact dermatitis.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There is no information available on the potential for the test substance to produce respiratory sensitisation in animals or humans.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the present data, classification for sensitization is not warranted under Regulation (EC) No.1272/2008.