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

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
Justification for non-LLNA method:
When the GPMT was performed, the LLNA did not yet exist as an OECD guideline.

Test material

Constituent 1
Chemical structure
Reference substance name:
Bumetrizole
EC Number:
223-445-4
EC Name:
Bumetrizole
Cas Number:
3896-11-5
Molecular formula:
C17 H18 Cl N3 O
IUPAC Name:
2-tert-butyl-6-(5-chloro-2H-1,2,3-benzotriazol-2-yl)-4-methylphenol
Test material form:
solid
Specific details on test material used for the study:
- Name of test material (as cited in study report): TK 10048
- Analytical purity: 100.1 %
- Lot/batch No.: EN 325964.12
- Expiration date of the lot/batch: June, 1996
- Storage condition of test material: Room temperature
- Physical state: solid

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: Ciba-Geigy Ltd, Animal Production, 4332 Stein, Switzerland
- Age at study initiation: adult
- Weight at study initiation: 352 - 409 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: NAFAG No. 845 (Gossau AG); ad libitum
- Water: ad libitum
- Acclimation period: 5 days

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

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
other: intradermal injections: Oleum arachidis and saline; epidermal applications: vaseline
Concentration / amount:
Intradermal injection: 0.1 mL of a 5% mixture of test substance in Oleum arachidis
Epidermal: 0.4 g of a 30% mixture of the test substance in vaseline

Challenge
Route:
epicutaneous, occlusive
Vehicle:
other: intradermal injections: Oleum arachidis and saline; epidermal applications: vaseline
Concentration / amount:
Epidermal: 0.2 g of a 20% mixture of the test substance in vaseline
No. of animals per dose:
10 animals/sex/dose
Details on study design:
PRE-TEST:
- 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. The following concentration of test article have been prepared for intradermal injection: 1 and 5% in oleum arachidis. Since 5% was well tolerated, this concentration was used for intradermal induction.
- The concentrations for 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 for the maximum subirritant concentration: 1, 5, 10 and 30% in vaseline. The tested concentrations did not induce erythema reactions. 30% were chosen for epidermal induction and 20% for epidermal challenge application.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous), one week between intradermal und epidermal exposure
- Exposure period: 48 h for epicutaneous
- Test groups: 1). FCA/saline 1:1 mixture, 2). test substance in Oleum arachidis, 3). test substance in FCA/saline mixture
- Control group: same as the test group with the exception that the test substance was ommited
- Site: neck
- Frequency of applications: single

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge: 29 (2 weeks after epidermal induction)
- Exposure period: 24 h
- Test groups: Test substance in vaseline and vaseline alone
- Control group: Vaseline and test substance on separate flanks
- Site: flank
- Evaluation (hr after end of challenge exposures): 24 and 48


Positive control substance(s):
yes
Remarks:
The sensitivity of the strain is checked every 6 months with at least one of the following known sensitiser: 2,4-dinitrochlorobenzene, paraphenylene diamine or potassium dichromate.

Results and discussion

Positive control results:
Positive control test performed using 1-chlor-2,4-dinitrobenzol between June 17, 1991 and July 18, 1991. In the test group, test article treated animals showed 10/10 animals with positive responses at 24 and 48 hours after challenge. Vehicle control animals showed 0/10 animals with positive responses at 24 and 48 hours after challenge. In the negative control group, there were 0/10 animals with positive responses at 24 and 48 hours after challenge in both the vehicle control and test article treated animals.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
20%
No. with + reactions:
1
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
20%
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10

Any other information on results incl. tables

Mean body weights (g)

Control

Test group

Control

Test group

Males

Females

Day 0

390

386

381

376

End of study

596

605

577

553

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met