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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Study was not conducted under GLP and reporting of results is limited.

Data source

Reference
Reference Type:
publication
Title:
Cutaneous tolerance to nitroxide free radicals and nitrone spin traps in the guinea pig
Author:
Fuchs J., Groth N., Herrling T.
Year:
1998
Bibliographic source:
Toxicology 126, 33–40

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Standardized performance according to Magnusson and Kligman (1969, J. Invest. Dermatol. 52, 268–76) and Schlede and Eppler (1995,Contact Dermatitis 32,1–4)
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study is publicly available, thererfore a new study was not conducted for animal welfare reasons.

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2,6,6-tetramethylpiperidinooxy
EC Number:
219-888-8
EC Name:
2,2,6,6-tetramethylpiperidinooxy
Cas Number:
2564-83-2
Molecular formula:
C9H18NO
IUPAC Name:
2,2,6,6-tetramethylpiperidinooxy
Test material form:
solid
Details on test material:
Handbok data

In vivo test system

Test animals

Species:
guinea pig
Details on test animals and environmental conditions:
TEST ANIMALS
- Species/Strain: Guinea pig
- Source: Charles River Wiga, Sulzfeld, Germany
- Body weigth: 300 to 400 g
- Housing: single housing in stainless steel cages
- Diet: Food pellets ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 60 %
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
100 or 10 mM
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
not disclosed
Day(s)/duration:
Day 8, 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
not disclosed
Day(s)/duration:
Day 24, 24 h
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
not disclosed
Day(s)/duration:
Day 24, 48 h
Adequacy of challenge:
highest non-irritant concentration
No.:
#3
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
not disclosed
Day(s)/duration:
Day 24, 72 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10
Details on study design:
Intradermal induction:
In the intradermal induction treatment, the animals are given the following injections at the beginning of the first week in the shoulder region on both the right and left sides. (1) Cranial injections: 0.1 ml Freunds complete adjuvans (1:1 with physiological saline); (2) medial injections: 0.1 ml of the test substance at a locally and systemically well tolerated concentration (10–100 mM in physiological saline; (3) caudal injections: 0.1 ml Freunds complete adjuvant plus test substance (1:1), final concentration of the test substance as for the medial injection.

Dermal induction:
In the dermal induction experiment on day 8, the test substance was applied at a concentration causing slight to moderate irritation in petrolatum to a filter paper and fixed to the site of application for 48 h. The animals were then left to rest until the challenge test. The negative controls are treated in the same way as the test animals, except that during the induction experiments, application of the test material is omitted. The positive controls were exposed to the skin sensitizer DNCB (0.01%).

Challenge:
In the challenge experiment on day 24, the test substance in the vehicle (petrolatum) was applied at a non-irritant concentration to the sheared flank on a filter paper (2x2 cm), fixed to the skin for 24 h under an occlusive covering.

Evaluation:
The treated area of the skin was cleaned and inspected 24, 48 and 72 h after removal of the occlusive patch. The skin reaction after challenge were assessed according to the Draize scale. Evaluation of the sensitizing potential of the substances is based on the number of the guinea pigs showing a positive degree of sensitization (score > 1) in comparison to the total numbers of animals tested.
Challenge controls:
negative control group with petrolatum
Positive control substance(s):
yes
Remarks:
DNCB (0.01%)

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.01%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10 mM, 100 mM
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item does not have skin sensitizing properties according to the standardized performance of the Magnuson and Kligman test. Thus, the available data on skin sensitivity of 2,2,6,6-tetramethylpiperidinooxy do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.