Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25.03.1985 - 25.04.1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD guidelines, no GLP statement, however QAU statement is included.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1981)
Qualifier:
according to
Guideline:
other: EEC directive 79/831
GLP compliance:
no
Remarks:
but QAU statement included
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: liquid
- Purity: commercial grade
- 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
- Age at study initiation: 10 weeks
- Weight at study initiation: 291 - 420 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: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 50 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: intradermal: sesame oil; epidermal: vaseline
Concentration / amount:
1% for intradermal application in sesame oil and saline adjuvant mixture
3% for epidermal application (Induction) in vaseline, about 0.4 g per patch
0.3% for epidermal application (Challenge) in vaseline, about 0.2 g per patch
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: intradermal: sesame oil; epidermal: vaseline
Concentration / amount:
1% for intradermal application in sesame oil and saline adjuvant mixture
3% for epidermal application (Induction) in vaseline, about 0.4 g per patch
0.3% for epidermal application (Challenge) in vaseline, about 0.2 g per patch
No. of animals per dose:
20 in test group, 10 in control group
Details on study design:
RANGE FINDING TEST
The concentrations of the test compound for induction and challenge periods were determined on separate animals. (no details given in the report).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (three pairs of intradermal injections and one epidermal applications)
- Exposure period: 48 hours (epidermal patch)
- Test group: 3 pairs of injections: Mixture of adjuvant and saline; test compound in vehicle; mixture of test compound in vehicle plus adujvant/saline mixture
- Control group: treated with adjuvant and vehicle
- Site: neck
- Duration: 1 week (intradermal induction) and 2 weeks (epidermal induction)
- Concentrations: 1% intradermally and 3% epidermally

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: two weeks after epidermal induction
- Exposure period: 24 hours
- Test groups: test substance
- Control group: treated with the vehicle as well as with test compound
- Site: flank
- Concentrations: 0.3%
- Evaluation (hr after challenge): 24 hours and 48 hours
Challenge controls:
The sensitivity of the strain is controlled every six month with p - phenylenediamine

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1 % intradermal, 0.3 % challenge
No. with + reactions:
15
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1 % intradermal, 0.3 % challenge. No with. + reactions: 15.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1 % intradermal, 0.3 % challenge
No. with + reactions:
15
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1 % intradermal, 0.3 % challenge. No with. + reactions: 15.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 % intradermal, 0.3 % challenge
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 % intradermal, 0.3 % challenge. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 % intradermal, 0.3 % challenge
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 % intradermal, 0.3 % challenge. No with. + reactions: 0.0. Total no. in groups: 10.0.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
75% of the animals were sensitized by the test article under the experimental conditions employed. The test article, is therefore considered to be a skin sensitizer.
Executive summary:

 In a maximization test according to OECD guideline 406 and performed under QAU surveillance, the test article was tested for sensitizing potential in Pirbright White guinea pigs. The test animals were first induced with three pairs of intradermal injections (adjuvant/saline; 1% test item in sesame oil; 1% test item in sesame oil plus adjuvant/saline). One week later, the animals were treated epicutanously for 48 hours with 3% test material in vaseline. Control animals received the vehicle alone during induction. Two weeks after induction, the animals were challenged by occlusive epicutaneous exposure (0.3 % concentration) for 24 hours. During the challenge, the control 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. Twenty four hours after removing the dressings the challenge reactions were graded according the Draize scoring scale. A second evaluation is made 48 hours after removing the dressings. In the test group, 15/20 animals showed skin reactions, whereas in the control group no skin reactions could be observed. In animals treated with the vehicle alone, no skin reactions could be observed either. The test article is therefore considered to be skin sensitizing and requires classification. The sensitivity of the strain is controlled every six month with p – phenylenediamine.