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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:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
2003

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Valid in vivo data with guinea pigs are available therefore no further needs to be performed

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-)
EC Number:
255-527-0
EC Name:
Sodium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-)
Cas Number:
41741-86-0
Molecular formula:
C34H24CrN8O6.Na
IUPAC Name:
Sodium;chromium(3+);2-[(3-methyl-5-oxido-1-phenylpyrazol-4-yl)diazenyl]benzoate
Test material form:
solid: particulate/powder

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Remarks:
Pirbright White Strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein / Switzerland
- Weight at study initiation: 336 to 402 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: ad libitum standard guinea pig pellets - NAFAG No. 845, Gossau SG
- Water: ad libitum

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
Vehicle:
arachis oil
Concentration / amount:
5%
Day(s)/duration:
3 pairs of injections
Route:
epicutaneous, occlusive
Vehicle:
other: Vaseline
Concentration / amount:
50%
Day(s)/duration:
48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Vaseline
Concentration / amount:
10 %
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 females and 10 males (test group)
5 females and 5 males (control group)
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 in a pretest. The following concentrations of test article have been prepared for intradermal injection: 5 % in Oleum arachidis. Since 5% test substance 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 of test substance have been examined on separate animals for the determination of the maximum subirritant concentration: 10, 20, 30, and 50% in vaseline. Erythema reactions were observed with 20, 30, and 50% in vaseline.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48h (epicutaneous)
- Test groups:
Interdermal (3 pairs of injections, 0.1 ml each):
Injection 1: adjuvant/saline mixture 1:1 (v/v)
Injection 2: test article in Oleum arachidis (w/v)
Injection 3: test article in the adjuvant/saline mixture (w/v)
Epicutaneous: test substance in vaseline (w/w), occluded
- Control group: was treated with adjuvant and the vehicle during the induction period
- Site: neck (intradermal and epicutaneous)
- Concentrations: intradermal: 5%, epicutaneous: 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: week 5
- Exposure period: 24 hours
- Test groups: test substance and vehicle only
- Control group: test substance and vehicle only
- Site: flank
- Concentrations: 10%
- Evaluation (hr after challenge): 24 and 48 hours

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
11
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
15
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
55 and 75% of the animals were sensitised by the test article under the experimental conditions employed. According to the maximisation gradingthe test item showed a moderate t strong grade of skin-sensitising (contact allergenic) potential in albino guinea pigs.
Executive summary:

The test substance was investigated for its sensitizing potential in a GLP-compliant Maximization test according to OECD guideline 406. Pirbright White guinea pigs received intradermal induction treatments with 5% in oleum arachidis and one epicutanous induction treatment with 50% in vaseline. For intradermal induction, three pairs of injections (adjuvant/saline; test item in vehicle; test item in adjuvant/saline) were given. Epidermal challenge was performed by occlusive application for 24 h two weeks later (10% in vaseline). The control group was exposed to vehicle only during this procedure. 55 and 75% of the animals were sensitised by the test article under the experimental conditions employed. In conclusion, the test substance is considered to be a skin sensitizer in albino guinea pigs.