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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
13.REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to Read-Across Justification Document in chapter 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to Read-Across Justification Document in chapter 13.

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to Read-Across Justification Document in chapter 13.

4. DATA MATRIX
Please refer to Read-Across Justification Document in chapter 13.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
July 03rd 1989, August 03rd 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted in 1989 when the GPMT was an internationally accepted and recommended method.
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Animal strain as given in the report: Pirbright White Strain (Tif: DHP)
- Source: CIBA-GEIGY Limited, Tierfarm, 4332 Stein / Switzerland
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: 336 to 446 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: standard guinea pig pellets - NAFAG No. 845, Gossau SG, ad libitum
- Water: fresh water, ad libitum

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

All batches of the diet are assayed for nutritive ingredients and contamination level by the manufacturer. Analytical results are available at the animal supply office. The drinking water is examined periodically by the IWB (Industrielle Werke Basel).
Route:
intradermal
Vehicle:
other: sesame oil
Concentration / amount:
10 %
Day(s)/duration:
day 0
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
10 %
Day(s)/duration:
day 7 / 48 h
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
10 %
Day(s)/duration:
day 21 / 24 h
No. of animals per dose:
10 male and 10 female guinea pigs per group
Details on study design:
The following concentrations have been examined on separate animals for the evaluation of the primary irritant potential and the maximum subirritant concentration: 30 and 10 % in vaseline.
Erythema reactions were observed with 30% in vaseline. 30% was, therefore, selected for the epidermal induction application and 10% as maximum subirritant concentration for the epidermal challenge application.

The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later.
First Induction, intradermal application
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 in sesame oil (w/v)
- test article in the adjuvant saline mixture (w/v)
Second Induction, epidermal application
One week later the test article 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).

Challenge
Two weeks after the epidermal induction application the animals were tested on the flank with test material in vaseline (w/w) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration for 24 hours).

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 sensitising potential of the test item was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the test.

Observations and records
Induction reactions
After the intradermal and the epidermal induction application irritant reactions are normally induced by the adjuvant, the high test article concentration, or the sodium lauryl sulfate pretreatment. Because most of the reactions are treatment related and not compound related, the reactions are only described in special cases in the section of results.
Challenge reactions
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 sensitising potential of the test item was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the test.
Challenge controls:
A control group 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 (at least 10 animals) to check the maximum subirritant concentration of the test article in adjuvant treated animals.
Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Interpretation of results:
GHS criteria not met
Conclusions:
In the GPMT, none of the guinea pigs of the test group showed skin reactions 24 and 48 hours after challenge with 10% test item.
Reason / purpose for cross-reference:
read-across: supporting information
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
August 25 to September 25, 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted in 1987 when the GPMT was an internationally accepted and recommended method.
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Animal strain as given in the report: Pirbright White Strain (Tif: DHP)
- Source: CIBA-GEIGY Limited, Tierfarm, 4332 Stein / Switzerland
- Age at study initiation: approx. 10 weeks old
- Weight at study initiation: 336 to 462 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: standard guinea pig pellets - NAFAG No. 846, Gossau SG, ad libitum
- Water: fresh water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22+3°C
- Humidity: 30 to 70 %
- Photoperiod: 12 hours light cycle day

All batches of the diet are assayed for nutritive ingredients and contamination level by the manufacturer. Analytical results are available at the animal supply office. The drinking water is examined periodically by the IWB (Industrielle Werke Basel).
Route:
intradermal
Vehicle:
other: sesame oil
Concentration / amount:
3 %
Day(s)/duration:
day 0
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
3 %
Day(s)/duration:
day 7
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
3 %
Day(s)/duration:
day 21 / 24 h
No. of animals per dose:
10 male and 10 female guinea pigs per group
Details on study design:
The following concentrations have been examined on separate animals for the evaluation of the primary irritant potential and the maximum subirritant concentration: 30, 10, 3 and 1% in vaseline.
Erythema reactions were observed with 10 and 30% in vaseline. 30% was, therefore, selected for the epidermal induction application and 3% as maximum subirritant concentration for the epidermal challenge application.

The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later.
First Induction, intradermal application
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 in sesame oil (w/v)
- test article in the adjuvant saline mixture (w/v)
Second Induction, epidermal application
One week later the test item 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).

Challenge
Two weeks after the epidermal induction application the animals were tested on the flank with test material in vaseline (w/w) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration for 24 hours).

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 sensitising potential of the test item was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the test.

Observations and records
Induction reactions
After the intradermal and the epidermal induction application irritant reactions are normally induced by the adjuvant, the high test article concentration, or the sodium lauryl sulfate pretreatment. Because most of the reactions are treatment related and not compound related, the reactions are only described in special cases in the section of results.
Challenge reactions
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 sensitising potential of the test item was classified according to the grading of Magnusson and Kligman. The body weight was recorded at start and end of the test.
Challenge controls:
A control group 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 (at least 10 animals) to check the maximum subirritant concentration of the test article in adjuvant treated animals.
Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
3%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
3%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Interpretation of results:
GHS criteria not met
Conclusions:
In the GPMT, none of the guinea pigs of the test group showed skin reactions 24 and 48 hours after challenge with 3% test item.

Data source

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, 2-ethylhexyl ester
EC Number:
807-747-9
Cas Number:
144429-84-5
Molecular formula:
C25H42O3
IUPAC Name:
Benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, 2-ethylhexyl ester
Test material form:
liquid

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: CAS 125643-61-0
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: CAS 125643-61-0

Applicant's summary and conclusion