Registration Dossier

Administrative data

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:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: melt; yellow to dark yellow
- Storage condition of test material: room temperature

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, Animal Production, Switzerland
- Weight at study initiation: 327 - 425 g
- Housing: single
- Diet: standard guinea pig pellets, NAFAG No. 845, Gossau SG (ad libitum)
- Water: ad libitum
- Acclimation period: yes, not further specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12


Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: intradermal and epicutaneous, occlusive
Vehicle:
other: Oleum arachidis or vaseline
Concentration / amount:
- induction phase: intradermal: 1% (in Oleum arachidis); epicutaneous: 50% (in vaseline);
- challenge phase: 50% (in vaseline);
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Oleum arachidis or vaseline
Concentration / amount:
- induction phase: intradermal: 1% (in Oleum arachidis); epicutaneous: 50% (in vaseline);
- challenge phase: 50% (in vaseline);
No. of animals per dose:
- test group: 10 males and 10 females;
- control group: 5 males and 5 females;
Details on study design:
RANGE FINDING TESTS:
The following concentrations of test article have been prepared for intradermal injection: 1, 3, and 5 % in Oleum arachidis. In a pretest 3 and 5% in Oleum arachidis induced skin necrosis at the injection sites. Therefore 1% in Oleum arachidis was used for intradermal induction.
The following concentrations of TK 11831 have been examined on separate animals for the determination of the maximum subirritant concentration: 1, 5, 10, 20, 30, and 50% in vaseline. Erythema reactions were observed with 30 and 50% TK 11831 in vaseline. Therefore 50% in vaseline was used for epidermal induction and challenge phase.

MAIN STUDY
A. INDUCTION EXPOSURE
First inductionweek, intradermal injection:
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 TK 11831 in Oleum arachidis (w/v)
- test article TK 11831 in the adjuvant/saline mixture (w/v)
Second inductionweek, epidermal application:
In the second week of induction TK 11831 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).
Rest period:
During weeks 3 and 4 no treatments were performed.
- Control group: treated with adjuvant and the vehicle
- Site: neck region
- Concentrations: intradermal: 1% (in oleum arachidis); epidermal: 50% (in vaseline);


B. CHALLENGE EXPOSURE
The animals were tested on the flank with TK 11831 in vaseline (w/w) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration for 24 hours).
- No. of exposures: 1
- Control group: treated with the vehicle as well as with the test article to check the maximum subirritant concentration of the test article in adjuvant treated animals
- Site: flank
- Concentrations: 50% in vaseline
- Evaluation (hr after challenge): 24 and 48 h after removing the dressings, the challenge reactions were graded according to the Draize scoring scale

Positive control substance(s):
yes
Remarks:
see below (positive control results)

Results and discussion

Positive control results:
The sensitivity of the strain is checked once or twice per year with a known sensitiser, such as mercaptobenzothiazole, benzocaine, or potassium-dichromate. The results of the latest positive control test are presented in this report.

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:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
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: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
other: challenge control (no treatment in the induction period)
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: challenge control (no treatment in the induction period). Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: challenge control (no treatment in the induction period)
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: challenge control (no treatment in the induction period). Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
18
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 18.0. Total no. in groups: 20.0.

Any other information on results incl. tables

Vehicle controls (treatment only in the induction period): 24 h after challenge: 0/20; 48 h after challenge: 0/20;

Challenge reactions of the test group after epidermal application (mean Draize score):

24 h after removal of the dressing: erythema: 1.8; edema: 0.5;

48 h after removal of the dressing: erythema: 1.2; edema: 0.3;

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
According to the test conditions, the test substance has to be classified: Xi, R43 (EU) and Cat. 1 (GHS).