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Description of key information

Skin: not sensitising (OECD Guideline Study)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adapted July 17, 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
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
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 Limited, Animal Production, 4332 Stein / Switzerland
- Weight at study initiation: 303 to 400 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
Route:
intradermal
Vehicle:
arachis oil
Concentration / amount:
5%
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
50%
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
50%
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. The tested concentrations did not induce erythema reactions, therefore 50% test article was selected for epidermal induction and challenge.

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: 50%
- Evaluation (hr after challenge): 24 and 48 hours

OTHER:
Epidermal induction: No skin irritation was observed in the pretest. Therefore the application site was pretreated with 10% sodium-laurylsulfate (open application) 24 hours prior to the epidermal induction application.
Positive control substance(s):
yes
Remarks:
Potassiumdichromate
Positive control results:
The following concentrations of the reference compound and vehicles were used:
Intradermal induction: Concentration of compound: 0.2%, Vehicle: physiological saline
Epidermal induction: Concentration of compound: 5%, Vehicle: vaseline
Epidermal challenge: Concentration of compound: 1%, Vehicle: vaseline

Result: 90% of the tested animals in the test group showed positive reactions whereas 0% positive results were found in control group.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
20
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions employed, none of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings. The test substance is therefore classified as not sensitising to skin in albino guinea pigs according to EU and GHS classification criteria.
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 (50% in vaseline). The control group was exposed to vehicle only during this procedure. No skin reactions were observed either for control or test group animals and therefore no animal was sensitized by the test article under the experimental conditions employed. The sensitivity of the strain is controlled every six month with p - phenylenediamine. In conclusion, the test substance is not considered to be a skin sensitizer in albino guinea pigs.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

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 epicutaneous 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 (50% in vaseline). The control group was exposed to vehicle only during this procedure. No skin reactions were observed either for control or test group animals and therefore no animal was sensitized by the test article under the experimental conditions employed. The sensitivity of the strain is controlled every six month with p - phenylenediamine. In conclusion, the test substance is not considered to be a skin sensitizer in albino guinea pigs and does not require classification. This finding is further supported by repeated insult patch conducted with 50 human volunteers. The test article did not elicit visible skin changes or sensitisation on any of the human subjects (see chapter 7.10.4)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the present data, classification for sensitization is not warranted under Regulation (EC) No.1272/2008.