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Description of key information

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:
07 Oct - 07 Nov 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Ministry of Environment, Nature Protection and Regional Planning, Potsdam, Germany
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Tierzucht Schönwald GmbH, Schönwalde, Germany
- Weight at study initiation: 356 - 406 g
- Housing: 2-3 animals per cage in polycarbonate macrolone cages (type IV) on softwood sawdust
- Diet: Altromin 3122 (Altromin, Lage, Germany), ad libitum
- Water: with vitamin C enriched domestic quality water acidified to pH 2.5, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: intradermal induction: peanut oil; dermal induction and challenge: ethanol/diethylphthalate (1:1)
Concentration / amount:
Induction: intradermal 2.5%, epicutaneous 100%
Challenge: epicutaneous 100%
Route:
epicutaneous, occlusive
Vehicle:
other: intradermal induction: peanut oil; dermal induction and challenge: ethanol/diethylphthalate (1:1)
Concentration / amount:
Induction: intradermal 2.5%, epicutaneous 100%
Challenge: epicutaneous 100%
No. of animals per dose:
10 (controls), 20 (test group)
Details on study design:
RANGE FINDING TESTS:
A range finding study was performed to determine the appropriate dose level of the test substance following intradermal and epicutaneous administrations. The intradermal irritancy of the test substance was investigated in order to find the minimal irritant test substance concentration for the intradermal induction. The epicutaneous irritancy of the test substance was investigated in order to find the minimal irritant test substance concentration for the dermal induction, and the maximum non-irritating test substance concentration for challenge application. For the intradermal administration test item concentrations of 0.6, 1.25, 2.5 or 5% were injected intradermally in two animals each. Slight skin reactions were observed at all test concentrations in all animals after 24 h and 48 h after application.
For the epicutaneous administration test item concentrations of 12.5, 25, 50 and 100% were applied to the clipped skin of two animals. No skin reactions were observed up to the highest concentration tested 24 and 48 h after removal of the patch.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture FCA/sterile distilled water
Injection 2: test substance in peanut oil
Injection 3: equal amounts of 5% test substance and FCA/sterile water in a 1:1 mixture (v/v)
Epicutaneous: undiluted test substance
- Control group:
Injection 1: a 1:1 mixture FCA/sterile distilled water
Injection 2: peanut oil
Injection 3: equal amounts of peanut oil and FCA in a 1:1 mixture (v/v)
Epicutaneous: ethanol/diethylphthalate (1:1)
- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 0-7
- Concentrations: intradermal 2.5%, epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 21
- Exposure period: 24 h
- Test groups: undiluted test substance and ethanol/diethylphthalate (1:1)
- Control group: undiluted test substance and ethanol/diethylphthalate (1:1)
- Site: right anterior flank (test substance) and left anterior flank (ethanol/diethylphthalate (1:1))
- Concentrations: 100%
- Evaluation: 24 and 48 h after patch removal
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
hexylcinnamaldehyde, induction: intradermal 10%, epicutaneous 100%, challenge: 100%
Positive control results:
The positive control substance induced positive reactions (score 2 and 3) in 6/10 animals (60% second reading), thus meeting the reliability criteria for the Guinea Pig Maximisation Test (≥ 30% positive response). The positive control group was not carried out concurrently with this study but is a historical background data group from a study performed during June 1997.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Induction: 0%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 2.5%; challenge: 100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction: 2.5%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Induction: 10%; challenge: 100%
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: Induction: 10%; challenge: 100%. No with. + reactions: 8.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Induction: 0%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 2.5%; challenge: 100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction: 2.5%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Induction: 10%; challenge: 100%
No. with + reactions:
6
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: Induction: 10%; challenge: 100%. No with. + reactions: 6.0. Total no. in groups: 10.0.

The challenge with undiluted test item revealed slight erythema (score 1) in 11 of 20 animals after 24 h. After 48 h one animal showed slight erythema (score 1).

The challenge with ethanol/diethylphthalate (1:1) revealed slight erythema (score 1) in 3 of 20 animals after 24 h. After 48 h no skin reactions were observed.

A slight or discrete erythema scored with „1" is not considered as a allergic reaction. The slight skin reactions were only seen in the test group. Some of the animals with this erythema showed a similar reaction on the patch area treated with the vehicle. After 48 h all skin reactions, except in one animal, disappeared. Therefore it is assurned, that the observed skin reactions were not caused by the treatment with the test article.

The animals showed normal body weight gain during the study period.

The animals showed no signs of ill health.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test the test substance revealed no sensitising properties.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:
Migrated from Short description of key information:
skin sensitisation (OECD 406): not sensitising

Justification for selection of skin sensitisation endpoint:
There is only one study available.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Justification for selection of respiratory sensitisation endpoint:
Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

The available data on sensitisation do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.