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Toxicological information

Skin sensitisation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
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.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: 99.1%
- Physical state: solid, powder

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: Sesame oil
Concentration / amount:
1%
Route:
epicutaneous, occlusive
Vehicle:
other: Vaseline
Concentration / amount:
30%
Challenge
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.

Results and discussion

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.

In vivo (non-LLNA)

Resultsopen allclose all
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

Applicant's summary and conclusion

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.