Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992-02-24 to 1992-05-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant; Guideline Study (OECD 406)

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
April 25, 1984
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
May 12, 1981
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical properties: powder;
- Storage conditions: 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; 4332 Stein / Switzerland
- Age at study initiation: not stated;
- Weight at study initiation: 346 - 425 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: 5 days;

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3°C,
- Humidity: relative humidity of 30 to 70%;
- Air changes (per hr): not stated;
- Light cycle: 12 hours light cycle/day;

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: vaseline (epidermal treatment); physiological saline ( intradermal treatment)
Concentration / amount:
Intradermal induction: 5 % in physiological saline;
Epidermal induction: 30 % of the test article in vaseline;
Epidermal challenge: 10 % of the test article in vaseline;
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline (epidermal treatment); physiological saline ( intradermal treatment)
Concentration / amount:
Intradermal induction: 5 % in physiological saline;
Epidermal induction: 30 % of the test article in vaseline;
Epidermal challenge: 10 % of the test article in vaseline;
No. of animals per dose:
10 male/10 females in the test group;
5 males/5 females in the control group;
Details on study design:
RANGE FINDING TESTS:
The concentrations for the epidermal applications were selected on account of the primary irritation potential of the test article. The following concentrations of the test item have been examined on separate animals for the determination of the maximum subirritant concentration:
1, 5, 10, and 30% in vaseline.
The tested concentrations did not induce erythema reactions.
Because a higher concentration may lead to nonspecific reactions in adjuvant treated animals, the test article concentration of 10% in vasiline was chosen as subirritant for the challenge application.

MAIN STUDY
A. INDUCTION EXPOSURE
First induction week, 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 in physiological saline (w/v)
- test article in the adjuvant saline mixture (w/v)
Second induction week, epidermal application:
In the second week of induction the test item 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
- No. of exposures: 1
- Day(s) of challenge: during week 5
- Exposure period: 24 hours;
- Test groups: 10 males / 10 females;
- Control group: 5 males / 5 females;
- Site: flank
- Concentrations: 10 % in vaseline
- Evaluation (hr after challenge): 24 h; 48 h;

C. CONTROL GROUP
- A control group of 10 animals (5 m/5 f) 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 to check the maximum subirritant concentration of the test article in adjuvant treated animals.

Positive control substance(s):
yes
Remarks:
Potassium dichromate

Results and discussion

Positive control results:
Results of the latest positive control test (perfomred every six months)

The following concentrations of the reference compound (potassium dichromate) and vehicles were used:
Intradermal induction: Concentration of compound: 0.2%, Vehicle: physiological saline
Epidermal induction: Concentration of compound: 5%, Vehicle: vaseline
Epidermal challenge: Concentration of compound: 1%, Vehicle: vaseline

Number of positive animals per group after occlusive epidermal application:
Control group: after 24 hours: vehicle control: 0/10; test article: 0/10; after 48 hours: vehicle control: 0/10; test article: 0/10;
Test group: after 24 hours: vehicle control: 0/10; test article: 7/10; after 48 hours: vehicle control: 0/10; test article: 6/10;

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
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.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
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: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
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.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
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: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Under the experimental conditions employed, none of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU