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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 04, 1986 to March 06, 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline study performed under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Data available from historic non-LLNA study.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy Ltd. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 339 - 463 grams
- Housing: individually in macrolon type 3 cages
- Diet (e.g. ad libitum): guinea pig pellets - NAFAG No. 486, Gossau SG.
- Water (e.g. ad libitum): Fresh water
- Acclimation period: 8 days

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: The intradermal induction was performed with adjuvant saline and sesame oil. The epidermal induction and challenge were performed with vaseline.
Concentration / amount:
The substance at 0.1% in sesame oil or adjuvant saline during the intradermal induction.
The substance at 30% in vaseline was used during the epidermal induction.
The substance at 10% in vaseline was used during the challenge procedure.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: The intradermal induction was performed with adjuvant saline and sesame oil. The epidermal induction and challenge were performed with vaseline.
Concentration / amount:
The substance at 0.1% in sesame oil or adjuvant saline during the intradermal induction.
The substance at 30% in vaseline was used during the epidermal induction.
The substance at 10% in vaseline was used during the challenge procedure.
No. of animals per dose:
Control group: 10 males and 10 females
Test group: 10 males and 10 females
Details on study design:
RANGE FINDING TESTS:
The concentration of the test compound for the induction and challenge periods were determined on separate animals.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: one intradermal exposure and one epidermal exposure
- Exposure period: First induction week: intradermal induction
Second induction week: epidermal induction
- Test groups:
Intradermal Induction:
1) adjuvant / saline mixture 1:1 (v/v)
2) substance at 0.1% in sesame oil (v/v)
3) substance at 0.1% in sesame oil and adjuvant/saline mixture (v/v)
Epidermal Induction:
The substance at 30% in vaseline
- Control group:
The control animals were treated with adjuvant and vehicle during the induction period.
- Site: The intradermal induction was performed on the sahved neck of the guinea pigs. The epidermal induction was performed over the injection sites.
- Frequency of applications: One week after the intradermal induction injections the epidermal induction application was performed.
- Duration:
Three pairs of intradermal injections made simultaneously for the intradermal induction.
Colsed patch exposure for 48 hours for the epidermal induction.
- Concentrations:
0.1 mL of the substance at 0.1% for the intradermal induction
0.4 g of the substance at 30% for the epidermal induction

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge: week 5
- Exposure period: 24 hours
- Test groups:
The animals were treated with the substance in vaseline (w/w) and the vehicle alone by occluded administration.
- Control group:
The animals were treated with the vehicle alone as well as with the maximum subirritant concentration of the substance
- Site: Flank
- Concentrations: 0.2 g of the substance at 10% in vaseline
- Evaluation (hr after challenge): 24 hours and 48 hours after removal of the dressings.
Positive control substance(s):
yes
Remarks:
paraphenylene-diamine or potassium-dichromate

Results and discussion

Positive control results:
no data provided in the report

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
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: 10%. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
19
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: 19.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
vehicle
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: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
vehicle
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: vehicle. 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:
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.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Under the experimental conditions employed, 100% of the animals of the test group showed skin reactions after the challenge application.
The substance is, therefore, classified as skin sensitiser in albino guinea pigs.
Executive summary:

In order to assess the cutaneous allergenic potential of the substance, the Maximisation-Test was performed in 40 (20 test and 20 control) males and females albino guinea pigs, in accordance with OECD Guideline No. 406 and the Directive 79/831/EEC.

The intradermal induction of sensitization in the test group was performed in the nuchal region with a 0.1% dilution of the test item in sesame oil and in mixture of Adjuvant saline. The epidermal induction of sensitization was conducted for 48 hours under occlusion with the test item at 30 % in vaseline one week after the intradermal induction. The animals of the control group were induced with the vehicle and Adjuvant saline.

Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the test item at 10 % in vaseline and vaseline alone under occlusive dressing.

Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.20 out of 20 animals (100%) after 24 hours and 19 out of 20 animals (95%) after 48 hours showed positive skin reactions after the challenge procedure with the substance at 10% in vaseline, no skin effects were noted in the test animals when treated with the vehicle alone. No control animal showed effects when treated with the substance at 10% in vaseline or when treated with vaseline alone. Based on the above mentioned findings the substance is considered to be a skin sensitiser.