Registration Dossier

Administrative data

Description of key information

The structural analogue substance does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test.

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:
1997/1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Method was not available
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River GmbH - Wiga, Kisslegg, Germany
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Microbiological status of animals, when known:
- Age at study initiation: young adults
- Weight at study initiation: 322 - 436 g
- Housing: 5/cage
- Diet (e.g. ad libitum): Kliba Labordiat 341 (Kaninchen-Meerschweinchen-Haltungsdiat) ad libitum
- Water (e.g. ad libitum): Water ad libitum (tap water; about 2 g of ascorbic acid per 10 L water was added to the drinking water twice a week)
- Acclimation period: 14 days
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12
- In-life dates: From April 25, 1995 To May 26, 1995.
Route:
intradermal
Vehicle:
olive oil
Concentration / amount:
5%: four injections a 0.1 mL
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, semiocclusive
Vehicle:
olive oil
Concentration / amount:
50%
Day(s)/duration:
on Day 8 - 48 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
50%
Day(s)/duration:
on Day 15 - for 24 hours
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
50%
Day(s)/duration:
on Day 22 - for 24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Main test
Number of animals per control group: 10
Number of animals of the test group: 20
Details on study design:
RANGE FINDING TESTS:
Determination of the primary non-irritant concentration
Determination of the tolerance of the intradermal injections

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal + 1 epicutaneous
- Exposure period: intradermal: 24 hours; epicutaneous: 48 hours
- Test groups: 1
- Control group: 2
- Site: shoulder
- Frequency of applications: Day 1; Day 8
- Duration: 24 and 48 hours
- Concentrations: 5 and 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: Day 22 and Day 29
- Exposure period: 24 hours
- Test groups: 1
- Control group: 1 + 1
- Site: flank
- Concentrations: 50%
- Evaluation (hr after challenge): 24 and 48 hours after removal of patches

OTHER:
Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
a separate study is performed twice a year
Positive control results:
The positive control with Alpha-Hexylcinnamaldehyde techn. 85% showed that the test system was able to detect sensitizing compounds under the laboratory conditions chosen.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
8
Total no. in group:
18
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
2
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0
No. with + reactions:
1
Total no. in group:
18
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
7
Total no. in group:
19
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
7
Total no. in group:
18
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
1
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0
No. with + reactions:
1
Total no. in group:
18
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
4
Total no. in group:
19
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
18
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
19
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
0
No. with + reactions:
0
Total no. in group:
18
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
1
Total no. in group:
19
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
18
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
19
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
0
No. with + reactions:
0
Total no. in group:
18
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
19

Body weights: The expected body weight gain has generally been observed in the course of the study.

Mortality: One animal of control group 2 and 2 animals of the test group died 6, 8 or 10 days after the beginning of the study. Macroscopic examination revealed that the animals suffered from pneumonia.

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test under the test conditions chosen
Executive summary:

The test substance was tested for its sensitizing effect on the skin of the guinea pig in the Maximization Test based on the method of Magnusson and Kligman.

The intradermal induction with 5% test substance preparations caused slight oedema in all test group animals. The index for erythema could not be determined because of staining due to the colour of the test substance.

After the percutaneous induction with a 50% test substance preparation incrustation, partially open (caused by the intradermal induction) could be observed in addition to well-defined erythema and slight oedema in all test group animals. The application areas were stained due to the colour of the test substance but it was possible to clean the treated area thoroughly, thus the index for erythema could be determined.

Two challenges were performed 14 and 21 days after the percutaneous induction. After the first challenge with a 50% test substance preparation very slight to well-defined skin reactions were observed in test group animals and animals of control group 1. Olive oil DAB 10 applied as vehicle caused very slight to well-defined erythema in one test group animal and in animals of control group 1 and 2. The second challenge with a 50% test substance preparation did not cause any skin reactions in all animals. Olive oil DAB 10 caused very slight erythema in one animal of control group 2.

Based on the results of this study, it was concluded that the test substance does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test under the test conditions chosen.

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

The test substance was tested for its sensitizing effect on the skin of the guinea pig in the Maximization Test based on the method of Magnusson and Kligman.

The intradermal induction with 5% test substance preparations caused slight oedema in all test group animals. The index for erythema could not be determined because of staining due to the colour of the test substance.

After the percutaneous induction with a 50% test substance preparation incrustation, partially open (caused by the intradermal induction) could be observed in addition to well-defined erythema and slight oedema in all test group animals. The application areas were stained due to the colour of the test substance but it was possible to clean the treated area thoroughly, thus the index for erythema could be determined.

Two challenges were performed 14 and 21 days after the percutaneous induction. After the first challenge with a 50% test substance preparation very slight to well-defined skin reactions were observed in test group animals and animals of control group 1. Olive oil DAB 10 applied as vehicle caused very slight to well-defined erythema in one test group animal and in animals of control group 1 and 2. The second challenge with a 50% test substance preparation did not cause any skin reactions in all animals. Olive oil DAB 10 caused very slight erythema in one animal of control group 2.

Based on the results of this study, it was concluded that the test substance does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test under the test conditions chosen.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

No sensitising effect was observed with the structural analogue substance; hence, no classification is necessary.