Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-05-28 to 1985-06-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 406: Maximisation test in the Guinea pig) under GLP-like quality assurance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted May 12, 1981
Deviations:
no
GLP compliance:
no
Remarks:
QAU-statement included
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: solid
- Analytical purity: commercial grade
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxicology GU 2.5, CIBA-GEIGY AG Basel, Switzerland (bred on premises)
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 276 to 410 g
- Housing: Individually in Macrolon cages (type 3)
- Diet: ad libitum standard guinea pigs pellets (NAFAG No. 846, Gossau SG), supplemented with fresh carrots
- Water: fresh water ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 2 °C
- Relative humidity: 50 ± 10%
- Photoperiod: 12 hours light cycle day

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: physiological saline, sesame oil
Concentration / amount:
Intradermal Induction: 1% test item in sesame oil or phys. saline / CFA mixture
Epidermal Induction: 30% in vaseline approx. 0.4 g per patch
Epidermal Challenge: 10% in vaseline, approx. 0.2 g per patch
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: physiological saline, sesame oil
Concentration / amount:
Intradermal Induction: 1% test item in sesame oil or phys. saline / CFA mixture
Epidermal Induction: 30% in vaseline approx. 0.4 g per patch
Epidermal Challenge: 10% in vaseline, approx. 0.2 g per patch
No. of animals per dose:
Test item group: 10 males and 10 females
Control group: 10 males and 10 females
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- Test groups: 20 animals (10 m/10 f)
- Control group: 20 animals (10 m/10 f)
First, two intradermal injections (0.1 ml per injection) were made into the neck of the guinea pigs with a mixture of adjuvant and saline, with the test compound in sesame oil and with the test compound in the adjuvant saline mixture. Concentration of the test compound was 1%. Control animals received the same pairs of injections but without the test article (vehicle only).
One week later the test substance was incorporated in vaseline at a concentration of 30% (0.4 g) and applied on a filter paper patch to the neck of the animals (occlusive administration for 48 hours). Control animals were treated with vaseline alone.

B. CHALLENGE EXPOSURE
- No. of exposures: once
- Day(s) of challenge: two weeks after the epidermal induction
- Exposure period: 24 h occlusive application
- Site: on the flank of the guinea pig
- Concentrations: 10% test item in vaseline and the vehicle alone
- Evaluation: Twenty four hours after removing the dressings, the challenge reactions were graded according the Draize scoring scale

The concentrations of the test compound for induction and challenge periods were determined on separate animals.
Challenge controls:
A control group of 20 animals (10 m/10 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 item to check the maximum subirritant concentration of the test article in adjuvant treated animals.
Positive control substance(s):
no

Results and discussion

Positive control results:
The sensitivity of the strain was controlled every six months with p - phenylenediamine (PPD).

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10% test substance in vaseline
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10% test substance in vaseline
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10% test substance in vaseline
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10% test substance in vaseline
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Executive summary:

In a 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, the test article was incorporated in vaseline at a concentration of 30% and applied on a filter paper patch to the neck of the animals (occlusive administration for 48 hours). Two weeks after the epidermal induction application the animals were tested on the flank with 10% test substance in vaseline and the vehicle alone (24 h occlusive application). Twenty four hours after removing the dressings the challenge reactions were graded according the Draize scoring scale. A second evaluation was made 48 hours after removing the dressings. A control group (20 m/20 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 compound to control the maximal subirritant concentration of the test compound in adjuvant treated animals. No animal of the test group was sensitized by the test substance, all skin reactions at 24 and 48 hour time points were scored 0. Therefore, under the experimental conditions of this study, the test material is non-sensitizing when topically applied to albino guinea pigs.