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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:
November 7, 1990 - February 7, 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 1H-Benzotriazole-1-methanamine, N,N-bis(2-ethylhexyl)-6-methyl- and 2H-Benzotriazole-2-methanamine, N,N-bis(2-ethylhexyl)-5-methyl- and N,N-bis(2-ethylhexyl)-4-methyl-1H-benzotriazole-1-methylamine and 2H-Benzotriazole-2-methanamine, N,N-bis(2-ethylhexyl)-4-methyl- and N,N-bis(2-ethylhexyl)-5-methyl-1H-benzotriazole-1-methylamine
EC Number:
939-700-4
Molecular formula:
Unspecified
IUPAC Name:
Reaction mass of 1H-Benzotriazole-1-methanamine, N,N-bis(2-ethylhexyl)-6-methyl- and 2H-Benzotriazole-2-methanamine, N,N-bis(2-ethylhexyl)-5-methyl- and N,N-bis(2-ethylhexyl)-4-methyl-1H-benzotriazole-1-methylamine and 2H-Benzotriazole-2-methanamine, N,N-bis(2-ethylhexyl)-4-methyl- and N,N-bis(2-ethylhexyl)-5-methyl-1H-benzotriazole-1-methylamine
Details on test material:
- Physical state: liquid
- Analytical purity: a.i. 99%
- Expiration date of the lot/batch: October 1991
- Solubility in water: < 0.1 g/L
- 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: from Ciba Geigy Limited, Animal Production, 4332 Stein, Switzerland
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: between 338 and 437 g
- Housing: housed individually in Macrolon cages (Type 3)
- Diet: standard guinea pig pellets (NAFAG no. 845, Gossau SG); ad libitum
- Water: ad libitum
- Acclimation period: 8 days


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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: sesame oil for the intradermal induction and vaseline for the epidermal treatments.
Concentration / amount:
INDUCTION:
Intradermal injection: 3% in sesame oil
Epidermal application: 10% in vaseline

CHALLENGE:
Epidermal application: 3% in vaseline
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: sesame oil for the intradermal induction and vaseline for the epidermal treatments.
Concentration / amount:
INDUCTION:
Intradermal injection: 3% in sesame oil
Epidermal application: 10% in vaseline

CHALLENGE:
Epidermal application: 3% in vaseline
No. of animals per dose:
20 (10 males and 10 females)
Details on study design:
INDUCTION:
- 2-stage operation
- First induction: 3 pairs of intradermal injections (0.1 mL per injection) made simultaneously into the shaved neck of the guinea pigs as follows:
adjuvant/saline mixture 1:1 (v/v)
test article in sesame oil (3%) (w/v)
test article in the adjuvant saline mixture (w/v)
- Second induction: in the second week, the test article was incorporated in vaseline (10%) (w/w) and applied on a filterpaper patch to the neck of the animals (patch 2 x 4 cm, approximately 0.4 g paste per patch
Occluded administration for 48 hours.
A control group (20 animals: 10 males and 10 females) was treated with adjuvant and the vehicle during the induction period.

REST PERIOD:
no treatment performed during weeks 3 and 4

CHALLENGE:
Animals were tested on the flank with the test article in vaseline (3%) (w/w) or the vehicle alone (patch 2 x 2 cm, approximately 0.2 g paste per patch)
Occluded administration for 24 hours.
During the challenge period, the control group of the induction 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.
Challenge controls:
A control group (20 animals: 10 males and 10 females) was treated with adjuvant and the vehicle during the induction period.
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:
sensitivity checked every 6 months: potassium dichromate

Results and discussion

Positive control results:
Incidence of positive animals per group after epidermal challenges 24 hours after removing of bandages:
7/10 for erythema
5/10 for edema

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
3%
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
(effects only in females)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 3%. No with. + reactions: 5.0. Total no. in groups: 20.0. Clinical observations: (effects only in females).
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
3%
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
(effects only in females)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 3%. No with. + reactions: 5.0. Total no. in groups: 20.0. Clinical observations: (effects only in females).
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
3%
No. with + reactions:
8
Total no. in group:
20
Clinical observations:
(3 males, 5 females)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 3%. No with. + reactions: 8.0. Total no. in groups: 20.0. Clinical observations: (3 males, 5 females).
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
3%
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
(2 males, 5 females)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 3%. No with. + reactions: 7.0. Total no. in groups: 20.0. Clinical observations: (2 males, 5 females).
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No toxic symptoms
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No toxic symptoms.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No toxic symptoms
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No toxic symptoms.

Any other information on results incl. tables

Results of test group:

Males

Animal number

Challenge

1

2

3

4

5

6

7

8

9

10

24 h

Erythema

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

48 h

Erythema

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

Re-Challenge

 

24 h

Erythema

1

2

0

1

0

0

0

0

0

0

Edema

0

1

0

0

0

0

0

0

0

0

48 h

Erythema

2

2

0

0

0

0

0

0

0

0

Edema

1

1

0

0

0

0

0

0

0

0

 

Females

Animal number

Challenge

1

2

3

4

5

6

7

8

9

10

24 h

Erythema

0

1

1

0

1

1

1

0

0

0

Edema

0

1

2

0

1

1

1

0

0

0

48 h

Erythema

0

1

1

0

1

1

1

0

0

0

Edema

0

0

2

0

1

1

1

0

0

0

Re-Challenge

 

24 h

Erythema

0

2

2

1

0

1

2

0

0

0

Edema

0

1

1

0

0

0

1

0

0

0

48 h

Erythema

0

2s

2s

1

0

2

2s

0

0

0

Edema

0

1

1

0

0

1

2

0

0

0

s = scaling

In both control groups (vehicle control and test article treated control), there were 0/20 animals with positive responses at 24 and 48 hours after challenge.

Under the experimental conditions employed, 25% of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings.

Because the reactions were not very strong and the number of positive animals was at the threshold of significance, a second challenge was performed after a further rest period. The control group was not challenged again.

After the second challenge application, the number of positive animals was increased to 40% and the reactions intensified.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
25 to 40% of the animals were sensitised by the test substance under the experimental conditions employed.