3-ethyloxetane-3-methanol

Skin sensitisation

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

not specified

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

Study performed prior to adoption of the LLNA test method (OECD 429).

Test material

Test material information

Constituent 1

Reference substance name:

3-ethyloxetane-3-methanol

EC Number:

221-254-0

EC Name:

3-ethyloxetane-3-methanol

Cas Number:

3047-32-3

Molecular formula:

C6H12O2

IUPAC Name:

(3-ethyloxetan-3-yl)methanol

Specific details on test material used for the study:

- Name of test material (as cited in study report): Trimethylolpropane Oxetane.
- Physical state: Colourless liquid.
- Analytical purity: No information provided; treated as 100% pure.
- Purity test date: No information provided.
- Lot/batch No.: TT099-2
- Expiration date of the lot/batch: 31st December 1999
- Stability under test conditions: No information provided.
- Storage condition of test material: In a refrigerator in the dark.
- Other: Density: 1022 kg/m3.

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Himalayan Strain albino guinea pig.

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland.
- Age at study initiation: Approximately 4 - 5 weeks old.
- Weight at study initiation: Less than 500 grams.
- Housing: Group housing of 5 animals per labelled metal cage with wire-mesh floors and equipped with an automatic drinking system.
- Diet (e.g. ad libitum): Free access to standard guinea pig diet, including ascorbic acid (1000mg/kg).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark.

IN-LIFE DATES: From: To: No information provided.

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, semiocclusive

Vehicle:

water

Induction 2

Concentration / amount:

100% concentration

Challenge

Challenge 1

Route:

epicutaneous, semiocclusive

Vehicle:

water

Challenge 2

Concentration / amount:

100% concentration

No. of animals per dose:

20

Details on study design:

RANGE FINDING TESTS:
A preliminary study was conducted in order to select the test substance concentrations to be used in the main study. A series of test substance concentrations was used, with the starting concentration of 100% (undiluted) and subsequent concentrations taken from the series (50%, 20%, 10%, 5%, 2%, 1% and if needed, further lower concentrations using the same steps.
The test system, procedures and techniques were identical to those used in the main study, with animals between 4 and 9 weeks of age. Body weights may have exceeded 500 grams.
A series of 4 test substance concentrations was sued, the highest concentration being the maximum concentration that could technically be appled. Two different concentratiosn were applied (0.15ml each) per animal to the clipped flank using Metalline patches (2x3cm) mounted on Medical tape, which was held in place with Micropore tape and subsequently Coban elastic bandage. After 6 hours, the dressing were removed and the skin cleaned of residual test substance. The resulting dermal reactions were assessed for irritation 24 and 48 hours after exposure.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three exposures on days 1, 8 and 15.
- Exposure period: 6 hours exposure.
- Test groups: 0.5ml of undiluted test substance was applied epidermally using Metalline patches (2x3cm) mounted on medical tape which was held in place with Micropore tape and subsequently Coban elastic bandage. After 6 hours, the dressing were removed and the skin cleaned of residual test substance. Immediately after removal of the last induction application on day 15, the treated skin was assessed for irritation.
- Control group: The control animals were treated as described for the experimental animals except that vehicle alone was administered.
- Site: Left side of the scapular region.
- Frequency of applications: Days 1, 8 and 15.
- Duration: 6 hours
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: Single exposue on day 28.
- Day(s) of challenge: Day 28
- Exposure period: 6 hours.
- Test groups: The right flank of all animals was clipped and subsequently treated epidermally with the undiluted test susbtance and the vehicle (0.15ml of each), using patch test plasters. The patches were held in place with Micropore tape and subsequently with Covan elastic bandage. The dressings were removed after 6 hours and the skin cleaned of residual test substance and vehicle.
- Control group: Received same treatment as treated animals .
- Site: Right flank.
- Concentrations: 100%
- Evaluation (hr after challenge): The treated sites were assessed for challenge reactions 24 and 48 hours after removal of the dressings.

OTHER:

Challenge controls:

All animals, including control, were treated epidermally with the undiluted test susbtance and the vehicle (0.15ml of each), using patch test plasters. The patches were held in place with Micropore tape and subsequently with Covan elastic bandage. The dressings were removed after 6 hours and the skin cleaned of residual test substance and vehicle.

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin reactions were observed. No mortality occurred and no symptoms of systemic toxicity were observed in animals in the main study. Body weights and body weight gains were in the same range as controls over the study period.

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No skin reactions were observed. No mortality occurred and no symptoms of systemic toxicity were observed in animals in the main study. Body weights and body weight gains were in the same range as controls over the study period. .

Results 2

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Results as per 1st reading

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: Results as per 1st reading.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: Not applicable

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Not applicable

Any other information on results incl. tables

No additional information provided.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

There was no evidence that Trimethylolpropane Oxetane caused skin hypersensitivity in the guinea pig, since no responses were observed in the experimental animals in the challenge phase. Based on these results, Trimethylolpropane Oxetane is not sensitising to the skin.

Executive summary:

The potential of Trimethylolpropane Oxetane to cause hypersensitivity was assessed in a skin sensitisation study conducted in accordance with OECD Test Guideline 406 and EC Commission 96/54/EEC, Part B.6, using the Buehler method. A preliminary study was conducted prior to the main study to ascertain the test substance concentrations. In the main study, 20 experimental animals were epidermally treated on three occasions (Days 1, 8 and 15) with undiluted test substance and ten control animals were similarly treated but with vehicle alone. Two weeks after the last induction exposure, all animals were challenged with the undiluted test substance and the vehicle.

No skin reactions were evident after the challenge exposure in the experimental animals or in the control animals. There was no evidence that Trimethylolpropane Oxetane caused skin hypersensitivity in the guinea pig, since no responses were observed in the experimental animals in the challenge phase. Based on these results, Trimethylolpropane Oxetane was nto found to be a skin sensitiser.