Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Remarks:
CIBA-GEIGY Limited, Toxicology Services, Short-term Toxicology
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.
The test was conducted in 1993. However, the original Test Guideline (TG) for the determination of skin sensitization in the mouse, the Local Lymph Node Assay (LLNA; TG 429) was adopted in 2002.

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2,6,6-tetramethylpiperidin-4-ol
EC Number:
219-291-2
EC Name:
2,2,6,6-tetramethylpiperidin-4-ol
Cas Number:
2403-88-5
Molecular formula:
C9H19NO
IUPAC Name:
2,2,6,6-tetramethylpiperidin-4-ol
Details on test material:
- Name of test material (as cited in study report): TK 11725/1, HTMP
- Physical state: solid, white

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White Strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein / Switzerland
- Weight at study initiation: 300 to 431 g
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: physiolog. saline and vaseline
Concentration / amount:
1. induction: 1 % in physio. saline
2. induction: 50% in vaseline
challenge: 30% in vaseline
rechallenge: 10% in vaseline
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: physiolog. saline and vaseline
Concentration / amount:
1. induction: 1 % in physio. saline
2. induction: 50% in vaseline
challenge: 30% in vaseline
rechallenge: 10% in vaseline
No. of animals per dose:
20 for test group (10 females and 10 males)
10 for control group (5 females and 5 males)
Details on study design:
RANGE FINDING TESTS: The following concentrations of test article have been prepared for intradermal injection: 1, 3, and 5 % in physiological saline.
Because necrosis was observed with 3 and 5% the following concentration was used for intradermal induction: Concentration of test article : 1%
Vehicle: physiological saline.
The concentrations for the epidermal applications were selected on account of the primary irritation potential of the test article. The following concentrations of the test substance have been examined on separate animals for the determination of the maximum subirritant concentration: 10, 20, 30, and 50% in vaseline. Only minimal erythema reactions were observed with 50% test substance in vaseline. Therefore for epidermal induction 50% in vaseline, for epidermal challenge 30% in vaseline and epidermal rechallenge 10% were used.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 pairs of intradermal injections and one closed patch epidermal induction
- Exposure period: 2 weeks
- Test groups: 1
- Control group: 1
- Site: neck region
- Frequency of applications: once per week
- Duration: epidermal induction: 48 hours
- Concentrations: 1% intradermal, 50% epidermal


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: week 5
- Exposure period: 24 hours
- Test groups: 1
- Control group: 1
- Site: flank
- Concentrations: 30%
- Evaluation (hr after challenge): 24 and 48 hours

OTHER: Rechallenge: (week 6): 10% test substance in vaseline
Positive control substance(s):
yes
Remarks:
Potassiumdichromate

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
30%
No. with + reactions:
9
Total no. in group:
16
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30%. No with. + reactions: 9.0. Total no. in groups: 16.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
30%
No. with + reactions:
9
Total no. in group:
16
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30%. No with. + reactions: 9.0. Total no. in groups: 16.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
5
Total no. in group:
16
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 5.0. Total no. in groups: 16.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
11
Total no. in group:
16
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 11.0. Total no. in groups: 16.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
30%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 30%. No with. + reactions: 7.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
30%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 30%. No with. + reactions: 7.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 1%. No with. + reactions: 9.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
1%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 1%. No with. + reactions: 9.0. Total no. in groups: 10.0.

Any other information on results incl. tables

- In all animals of the test group hunched posture, piloerection, and sedation were observed on experimental day 11. Hunched posture and piloerection were observed in several animals up to experimental day 17.

- One moribund male and one female were sacrificed on experimental day 11 and 14, respectively. On experimental day 15 two females were found dead.

- Macroscopical investigations of all animals of the test and control group revealed a dilatation of the small and large intestine in two animals and a dilatation of the large intestine including caecum in further two animals, being common findings in moribund sacrificed guinea pigs or in guinea pigs found dead. Additionally, in one female multiple bilateral nodules of the kidneys were noted. All other animals of the test and control group were devoid of macroscopical changes indicative of systemic toxicity. Histopathological investigations were not considered necessary. Since initially symptoms were observed in all animals of the test group and with respect to the mortality recorded treatment-relation cannot be fully excluded.

- After the first challenge application 56% of the animals of the test group and 70% of the animals of the control group showed skin

reactions (erythema of score 1). After a second challenge application, using a lower test article concentration and a new control group, 31 and 69% of the animals of the test group were sensitised 24 and 48 hours after removing the dressings, respectively (erythema score 1, one animal also edema score 1). None of the animals of the control group showed skin reactions during the second challenge.

The test substance is therefore classified as a moderate to strong sensitiser in albino guinea pigs according to the grading of Magnusson and Kligman.

Applicant's summary and conclusion