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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:
From Sep. 18, 1991 to Feb. 4, 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study was performed in accordance with OECD guideline 406 (1981) and appears to follow the updated guideline 406 (1992) without deviation. Contains GLP certification statement. Dated and signed quality assurance inspection statements included.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
- 1981 followed, reliability scoring based on 1992 guideline
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
When the study was performed, the LLNA did not yet exist. The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report): TK 10047 (Tinuvin P)
- Physical state: solid
- Analytical purity: > 98.1%
- Lot/batch No.: EN 139879.82
- Expiration date of the lot/batch: September, 1993
- Storage condition of test material: Room temperature
Specific details on test material used for the study:
- Name of test material (as cited in study report): TK 10047 (Tinuvin P)
- Physical state: solid
- Analytical purity: > 98.1%
- Lot/batch No.: EN 139879.82
- Expiration date of the lot/batch: September, 1993
- Storage condition of test material: Room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: CIBA-GEIGY Limited (Animal Production) 4332 Stein/Switzerland- Age at study initiation: Not reported- Weight at study initiation: 354 to 433 g- Housing: Housed individually in Macrolon cages (Type 3)- Diet (e.g. ad libitum): standard guinea pig pellets NAFAG No. 845, Gossau SG, ad libitum- Water (e.g. ad libitum): fresh water, ad libitum- Acclimation period: 6 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 22 ± 3- Humidity (%): 30 to 70- Air changes (per hr): Not reported- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
arachis oil
Concentration / amount:
5%
Day(s)/duration:
single injection
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
30%
Day(s)/duration:
48h
Adequacy of induction:
highest technically applicable concentration used
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
20%
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Test group: 10/sex
Control group: 5/sex
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. 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: 1, 5, 10, and 30% in vaseline (no other details provided).

MAIN STUDY
Control group: One side of flank induced with vehicle and challenged with vehicle; other side of flank induced with vehicle and challenged with test substance
Test group: One side of flank induced with test substance and challenged with vehicle; other side of flank induced with test substance and challenged with test substance.

INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: single exposure (intradermal); 48 hours (epidermal)
- Test groups: First induction week, intradermal injection: Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shaved neck of the guinea pigs as follows:- adjuvant/saline mixture 1:1 (v/v)- test article 7 in Oleum arachidis (w/v)- test article in the adjuvant saline mixture (w/v)
Second induction week, epidermal application:In the second week of induction the substance was incorporated in vaseline (w/w) and applied on a filterpaper patch to the neck of the animals (patch 2x4 cm; approx. 0.4 g paste per patch; occluded administration for 48 hours).
- Control group: A control group of 10 animals (5 m/5 f) was treated with adjuvant and the vehicle during the induction period.
- Site: Intradermal injections into the neck region, followed by closed patch exposure over the injection sites
- Frequency of applications: Single dose exposures (intradermal injection in the first week and epidermal application in the second week)
- Duration: 0-8 days- Concentrations: 5% in vehicle (intradermal) and 30% in vaseline (epidermal)B. CHALLENGE EXPOSURE
- No. of exposures: 1- Day(s) of challenge: The animals were challenged at Week 5.
- Exposure period: 24 hours- Test groups: The animals were tested on the flank with the test material in vaseline (w/w) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration).- Control group: During the challenge period the group was treated with the vehicle as well as with the test article to check the maximum subirritant concentration of the test article in adjuvant treated animals.
- Site: flank- Concentrations: 20% in vaseline (epidermal challenge)
- Evaluation (hr after challenge): 24 and 48 hrsChallenge reactions: Twenty four and forty eight hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale (Appraisal of the Safety of chemicals in Foods, Drugs and Cosmetics (1959), The US Association of Food and Drug Officials (AFDO). General: The sensitising potential was classified according to the grading of Magnusson and Kligman.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:
During the challenge period the group was treated with the vehicle as well as with the test article to check the maximum subirritant concentration of the test article in adjuvant treated animals.
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzol

Results and discussion

Positive control results:
The sensitivity of the strain is checked every six months with a known sensitiser, such as 2,4-dinitrochlorobenzene, para-phenylene-diamine or potassium-dichromate). The number of positive animals per group after occlusive epidermal application (induced with sensitiser and challenged with sensitiser) was both 10/10 animals after 24 and 48 hours. The results of the latest positive control test were provided using 1-chloro-2,4-dinitrobenzol.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
20%
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
20%
No. with + reactions:
18
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
other: control (induced with vehicle, challenged with test article)
Dose level:
20%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: control (induced with vehicle, challenged with test article)
Dose level:
20%
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Results from other groups tested:

Number of positive animals per group after occlusive epidermal application (induced with vehicle and challenged with vehicle) after 24 hours: 0/10

Number of positive animals per group after occlusive epidermal application (induced with vehicle and challenged with vehicle) after 48 hours: 0/10

Number of positive animals per group after occlusive epidermal application (induced with test article and challenged with vehicle) after 24 hours: 0/20

Number of positive animals per group after occlusive epidermal application (induced with test article and challenged with vehicle) after 48 hours: 0/20

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
The substance is classified as a skin sensitiser in albino guinea pigs according to the grading of Magnusson and Kligman.