Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20-May to 10-June 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Study was not conducted in compliance with GLP, but is well documented and sufficient to cover this endpoint (conduction close to OECD 404). 3 male and 3 females animals were used, observation period was 21 days.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
3 male and 3 female amimals were used and observation period was 21 days after removal of patches.
GLP compliance:
no

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
Remarks:
color: orange
Details on test material:
purchased from Sigma Chemical Company, Munich, Germany.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Species/Strain: Rabbit (New Zealand albino)
- Source: R and B Enterprise, Hamilton OH
- Body weigth: 2.7 to 3.1 kg
- Housing: single housing in stainless steel cages
- Diet: Purina Lab Rabbit Chow HF #5325, 150 g daily
- Water: Water supplied from a reverse-osmosis purifier, ad libitum
- Acclimation period: 14 days befor the first test-substance application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 40 %
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Approximateyl 24 hours prior to study initiation, fur was clipped from an area of approximateyl 240 cm2 on the back of each rabbit. A 0.5 g quantity of the test article was applied uniformly to each test side and was covered with a 2.5 x 2.3 cm adhesive dressing.
Duration of treatment / exposure:
4 hours, afterwards application sites were rinsed with 0.9% saline
Observation period:
21 days
Number of animals:
3F / 3M
Details on study design:
Application sites were examined for signs of dermal irritiation and corrosivity 50-60 min, 24, 48, and 72 hours, and 7, 14, and 21 days following removal of the wrappings.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Remarks:
Animal was sacrificed after 72 h.
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Remarks:
Animal was sacrificed after 72 h.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Remarks:
Animal was sacrificed after 72 h.
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Remarks:
Animal was sacrificed after 72 h.
Irritant / corrosive response data:
Brown areas were seen within the test sites of all tested rabbits 30-60 minutes after removal of the wrappings and persisted through the 72-hour scoring interval. Eschar formation was apparent in five out of six rabbits at that time. Therefore, two rabbits exhibiting the strongest signs of dermal irritation (Nos 3 and 6) were sacrificed following the 72-hour scoring interval and most severely affected dermal sections were subjected to histopathological investigation and compared to untreated skin. As a result, severe necrosis of the epidermis and moderate necrosis of the dermis were observed in correlation with acute mild to moderate inflammation of the dermis. Deeper necrosis including adnexa was seen with foci distribution.
In the other four animals, eschar formation persisted through day 7 or day 14. Cracking and/or concavity of the test site was also seen during the study. New or repaired skin was evident within the test sites of three of the four remainign rabbits by day 21.

Applicant's summary and conclusion

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
Based on the irritation parameters and the histopathological evaluation following 4-hour occlusive test item application in an in vivo irritation/corrosion study in male and female rabbits, 2,2,6,6-tetramethylpiperidinooxy is considered to be corrosive to the skin.
As a conclusion, the test substance is classified for this endpoint in accordance to the CLP Regulation (EC) No 1272/2008 as corrosive to the skin, category 1C.