Registration Dossier

Administrative data

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
Reliability:
2 (reliable with restrictions)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
other: Pirbright White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation:327-333 g
- Housing: Makrolon cage type IV
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12h dark / 12 h light
Route:
intradermal and epicutaneous
Vehicle:
other: vaseline
Concentration / amount:
Intradermal induction: 0.5 % in soybean oil
epicutaneous induction: 10 % in vaseline
challenge: 1 % in vaseline
Concentration / amount:
Intradermal induction: 0.5 % in soybean oil
epicutaneous induction: 10 % in vaseline
challenge: 1 % in vaseline
No. of animals per dose:
- range finding test. 15
- main test: 20 test animals, 20 control animals
Details on study design:
RANGE FINDING TESTS: 3 tests were done with 5 guinea pigs each
- group A: intracutaneous application: 0.1, 0.5, 1.0, 2.0 % (vehicle: soybean oil)
- group B: dermal induction: 5, 10 % (vehicle: vaseline)
- goup C: intracutaneous injection of Freund's adjuvans (0.1 ml), in the 3rd week: dermal induction: 0.2 g of a 2.5 and 5% solution

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures:
- 1st induction: 6 intradermal injections (Freund'S Adjuvans, 0.5 % test item, Freund's Adjuvans + 1 % test item)
- 2nd induction: one week after intradermal induction, dermal inducation (10 % in vaseline)
- Exposure period: 48 h
- Test groups: 20
- Control group: 20

B. CHALLENGE EXPOSURE
- Day(s) of challenge: 14 days after last induction
- Exposure period: 24 h
- Concentrations: 1% in vaseline
- Evaluation (hr after challenge): 24, 48 h
Challenge controls:
no data
Positive control substance(s):
no
Positive control results:
no data
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1 % in vaseline
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1 % in vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1 % in vaseline
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1 % in vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

No changes in bodyweight gain were seen. No mortality occurred. No skin reactions were noted after challenge.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to these test results the test item can be classified as "no skin sensitizer" in the Magnusson-Kligman test on guinea pigs.
Executive summary:

The test substance was tested for its sensitization potential in guinea pigs, using the method of B. Magnusson and A. M. Kligman, J. Invest. Dermatol. 52, 268 -276 (1969). First the minimum irritant concentration for the induction application (intracutaneous and epidermal) and the maximum non irritant concentration for the challenge application were estimated in separate tests. For the main test 20 female test animale and 20 controls, Pirbright white strain, were used. The initial average body weight of the test group animals was 333.8 g, that one of the control animals was 314.0 g. The test substance was applied in oily dilutions. 24 and 48 hours after removing of the patches of the challenge application no skin reactions were observed on the test animals as well as on the control animals. According to these test results the test substance can be regarded as a "non sensitizer' for albino guinea pigs.

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

The evaluation of the skin sensitizing potential of RRR-(alpha-, beta-, gamma-, delta)-tocopherol is based on one in-vivo study with the test substance and three in-vivo studies with the a close homolog (RRR-alpha-tocopherol) and a reliable publication.

The skin sensitising potential of the test item was assessed using the Guinea pig maximization test. The assays are done according to the OECD guideline 406.

Key Study:

The test substance, RRR-(alpha-, beta-, gamma-, delta)-tocopherol, was tested for its sensitisation potential in guinea pigs, using the method of B. Magnusson and A. M. Kligman, J. Invest. Dermatol. 52, 268 -276 (1969). The test substance was applied in oily dilutions. 24 and 48 hours after removing of the patches of the challenge application no skin reactions were observed on the test animals as well as on the control animals. According to these test results the test substance can be regarded as a "non-sensitiser” for albino guinea pigs.

Supporting Study:

The study is done with a close homolog of the test substance, RRR-alpha-tocopherol.

For the GPMT 20 female test animals and 20 controls, Pirbright white strain, were used. For the dilution of the test concentration of the intracutaneous test soybean oil and for the epicutaneous application paraffinum album were used.

24 and 48 hours after the removing of the patches of the challenge application neither the test nor the control animals showed any skin reactions on the treated skin areas.

According to these test results the test item can be classified as "no skin sensitizer" in the Magnusson-Kligman test on guinea pigs.

Supporting Study:

The second supporting study was done with a close homolog of the test substance, RRR-alpha-tocopherol, according to the key study. 24 and 48 hours after the removing of the patches of the challenge application neither the test nor the control animals showed any skin reactions on the treated skin areas.

According to these test results the test item can be classified as "no skin sensitizer" in the Magnusson-Kligman test on guinea pigs.

Supporting Study:

This study was also done with a close homolog of the test substance, RRR-alpha-tocopherol.

The sensitising properties of RRR-alpha-tocopherol (Purity 87%) were evaluated in the guinea pig maximization test.

20 guinea pigs were used for the test group and 19 guinea pigs were used for the control group.

Sensitisation rates were 0/20 and 0/19 in the test and control group, respectively. The test substance was not a sensitiser under the conditions of this study.

The information available on the skin sensitizing potential of the test item show no need for a classification of the test item concerning skin sensitization.


Migrated from Short description of key information:
Skin sensitisation:
Key: not sensitising (GPMT)
Supporting: RA: 59-02-9, not sensitising (GPMT)
Supporting study: RA: 59-02-9, not sensitising (GPMT)
Supporting study: RA: 59-02-9, not sensitising (GPMT, publication)

Justification for selection of skin sensitisation endpoint:
Most reliable guideline study was choosen for classification.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

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