Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 23, 1995 - February 16, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Since a valid GPMT was available, no LLNA was performed

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: liquid
- 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:CIBA-GEIGY Limited, Animal Production
- Weight at study initiation: between 329 to 425 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: d libitum standard guinea pig pellets - NAFAG No. 845, Gossau SG
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
other: Oleum arachidis (intradermal), vaseline (epidermal)
Concentration / amount:
intradermal: 5%
epidermal: 20%
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Oleum arachidis (intradermal), vaseline (epidermal)
Concentration / amount:
10%
No. of animals per dose:
10 (test group)
5 (control group)
Details on study design:
RANGE FINDING TESTS:
The concentration for the intradermal injections was selected on account of the solubility of the test article in standard vehicles and its local and systemic tolerability in a pretest. Since 5% in Oleum arachidis could be injected and was well tolerated, this concentration was used for the intradermal induction. The concentrations for the epidermal applications were selected on account of the primary irritation potential of the test article. The following concentrations have been examined on separate animals for the determination of the maximum subirritant concentration: 10 and 20% in vaseline. 20% was the highest possible concentration of the test article in vaseline. Reactions were observed with 20% in vaseline.

MAIN STUDY
A. INDUCTION EXPOSURE
Three pairs of intradermal 0.1 ml injections (adjuvant/saline mixture 1:1 (v/v); 5% test article in Oleum arachidis (w/v); 5% test article in the adjuvant/saline mixture (w/v)) were made simultaneously into the left and right side of the shaved neck of the test and control group animals. The control group received the same injections without the test article. Eight days after the intradermal induction, the test article was incorporated in vaseline (w/w; 20%) and applied on a filterpaper patch to the neck of the animals (patch 2x4 cm; approx. 0.4 g per patch; occluded administration for 48 hours). The control group was treated with the vehicle only.

B. CHALLENGE EXPOSURE
Two weeks later, the test and control group animals were tested on one flank with the test article in vaseline (w/w; 10%) and on the other flank with the vehicle alone (patch 2x2 cm; approx. 0.2 g per patch; occluded administration for 24 hours). Twenty four and forty eight hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale.
Positive control substance(s):
yes
Remarks:
The sensitivity of the strain is checked once or twice a year with a known mild to moderate sensitiser. The results of the last control with 2-Mercaptobenzothiazole is included in the report.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
18
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
19
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:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
Under the experimental conditions employed, 90% and 95% of the animals of the test group were sensitised 24 and 48 hours after removing the dressings.