Registration Dossier

Administrative data

Description of key information

Study carried out according to guideline and with GLP compliance.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Jul. 17, 1985 to Aug. 15, 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
-no reasoning for moderately low dose selection given
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This study was conducted in 1985, before the LLNA guideline was adopted in 2002. This study is considered to be reliable with restrictions (2), under the crteria of Klimisch et al, 1997. No further LLNA testing is considered to be scientifically justified based upon humane grounds.
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 Ltd. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: Approximately 10 weeks old
- Weight at study initiation: 288 to 409 g
- Housing: Housed individually in Macrolon cages (Type 3)
- Diet (e.g. ad libitum): standard guinea pig pellets, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 to 70
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: sesame oil
Concentration / amount:
Induction period:
Intradermal application - 1% of Tk 12599 in sesame oil and adjuvant mixture
Epidermal application - Approximately 0.4 g paste of 30% TK 12599 in vaseline

Challenge exposures:
Dose of application - Approximately 0.2 g paste of 10% TK 12599 in vaseline
Route:
epicutaneous, occlusive
Vehicle:
other: sesame oil
Concentration / amount:
Induction period:
Intradermal application - 1% of Tk 12599 in sesame oil and adjuvant mixture
Epidermal application - Approximately 0.4 g paste of 30% TK 12599 in vaseline

Challenge exposures:
Dose of application - Approximately 0.2 g paste of 10% TK 12599 in vaseline
No. of animals per dose:
Induced with test article and challenged with test article = 10/sex
Induced with test article and challenged with vehicle only = 10/sex
Induced with adjuvant and challenged with test article = 10 male animals
Induced with adjuvant and challenged with vehicle only = 10/sex
Details on study design:
RANGE FINDING TESTS: Not reported

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: Three pairs of intradermal injections were administered once, followed by epidermal application 1 week later.
- Test groups:
First induction (intradermal application) - 3 injections consisted of 1) adjuvant and saline; 2) test compound TK 12599 in sesame oil; and 3) test compound TK 12599 in adjuvant mixture.
Second induction (epidermal application) - TK 12599 was incorporated in vaseline and applied on a filter paper patch to the neck of the animals (patch 2x4 cm; occluded administration for 48 hours).
- Control group: A control group was treated with the adjuvant and the vehicle during the first induction period.
- Site: neck
- Frequency of applications: Single dose exposures (intradermal applications were administered, and 1 week later, epidermal applications were applied)
- Duration: 0 to 8 days for induction period. Epidermal application = 48 hours
- Concentrations: Intradermal application - 1% of TK 12599 in sesame oil and adjuvant mixture
Epidermal application - Approximately 0.4 g paste of 30% TK 12599 in vaseline


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 22
- Exposure period: 24 hours
- Test groups: Two weeks after the epidermal induction application the animals were tested on the flank with TK 12599 in vaseline and the vehicle alone.
- Control group: Same as the test group
- Site: flank
- Concentrations: Approximately 0.2 g paste of 10% TK 12599 in vaseline
- Evaluation (hr after challenge): 24 and 48

Twenty four hours after removing the dressings, the challenge reactions were graded according to the Draize Scoring scale. A second evaluation was made 48 hours after removing the dressings.
The sensitizing potential of TK 12599 was classified according to the grading of Magnusson and Kligman, as shown below.

Maximization grading:
Sensitization rate (%) - Grade - Classification
0 - 8 - I - weak
9 - 28 - II - mild
29 - 64 - III - moderate
65 - 80 - IV - strong
81-100 - V - extreme
Challenge controls:
At least 10 animals were included in the control group (sex not reported). Dose levels used is the same level as the concentrations administered in the challenge test group animals.
Positive control substance(s):
yes
Remarks:
Paraphenylene-diamine or potassium-dichromate
Positive control results:
The sensivity of the strain is checked every six months with paraphenylene-diamine or potassium-dichromate (no other details provided).
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.2 g paste of 10% test item 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: 0.2 g paste of 10% test item 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:
0.2 g paste of 10% test item 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: 0.2 g paste of 10% test item 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:
0.2 g paste of 10% test item in vaseline
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.2 g paste of 10% test item in vaseline. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.2 g paste of 10% test item in vaseline
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.2 g paste of 10% test item in vaseline. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
paraphenylene-diamine or potassium-dichromate (no other details provided)
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
No details provided
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
paraphenylene-diamine or potassium-dichromate (no other details provided)
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
No details provided
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
The test item was found to be devoid of a skin sensitizing potential under the test conditions.
Executive summary:

In this guideline (OECD 406) study conducted with GLP certification, the test material was found to be non-sensitising to the Guinea pig. The test was conducted using the Guinea pig maximisation methodology. 10 Guinea pigs of each sex were induced with the test material in the vehicle, with a further 10 of each sex induced with the test material vehicle and adjuvant. The topical challenge stage was conducted 2 weeks after dermal induction. Responses were graded after a 24 hour exposure using the Draise system. The test material was determined not to meet the criteria for classification as a skin sensitiser under the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Procedure and results

To evaluate the allergic potential of the substance, a skin maximisation test in guinea-pig was perfomed. twenty test and ten control guinea-pigs were used in this study. For induction of animals, three pairs of intradermal injection (1%) were made. 6 days later, topical induction (30%) in the same area was performed after treatment with sodium lauryl sulphate in petrolatum. Control and test animals were challenged topically two weeks after the topical induction application using the test substance, 10 % w/v in distilled water.

No skin reactions or signs of toxicity were recorded. There were no dermal reactions seen in any of the test animals.

Discussion

The test substance did not provoke skin sensitization or any dermal reaction. Thus, the test substance is not considered to be skin sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008.