Oxacycloheptadecan-2-one

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 November 1994 - 13 December 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

yes

Remarks:

The study was extended to investigate 5 different concentrations of the test article and a vehicle control on each animal

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

29 December 1992

Deviations:

yes

Remarks:

The study was extended to investigate 5 different concentrations of the test article and a vehicle control on each animal

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pentadecan-15-olide

EC Number:

203-354-6

EC Name:

Pentadecan-15-olide

Cas Number:

106-02-5

Molecular formula:

C15H28O2

IUPAC Name:

oxacyclohexadecan-2-one

Test material form:

solid

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature in the dark
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: soluble in ethanol/diethyl phthalate 1:1 (w/w)

Test animals

Species:

rabbit

Strain:

other: Mol:Russian

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mollegaard Breeding and Research Centre A/S, Ejby, DK-4623 Lille Skensved
- Weight at study initiation: 2.0-2.3 kg
- Housing: single 62 x 52 cm PPO cages with perforated floor
- Diet (e.g. ad libitum): a pelleted complete rabbit diet "Altromin 2123" from Chr. Petersen, DK-4100 Ringsted, ad libitum.
- Water (e.g. ad libitum): bottles with domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28-11-1994 To: 13-12-1994

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: ethanol/diethylphthalate 1:1 (w/w)

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 100% (undiluted test substance), 20%, 10%, 5%, 1% in ethanol/diethylphthalate

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 0.5 mL ethanol/diethylphthalate 1:1 (w/w)

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72 hours, 7 and 14 days

Number of animals:

4 females

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm on a total of 6 test sites: 2 anterior located, 2 centrally located and 2 posterior located. In total 5 different concentrations and a vehicle control were tested on each animal.
- % coverage: 100
- Type of wrap if used: 1 cm wide adhesive tap, fixed with Scanpor tape, 4.5 cm width, loosely wound round the truml

REMOVAL OF TEST SUBSTANCE
- Washing (if done): soap and lukewarm water
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 1, 24, 48 and 72 hours, 7 and 14 days after the end of the exposure

SCORING SYSTEM:
- Method of calculation: Draize

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

100% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

1.58

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Results 2

Irritation parameter:

edema score

Remarks:

100% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.08

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Results 3

Irritation parameter:

erythema score

Remarks:

20% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Results 4

Irritation parameter:

edema score

Remarks:

20% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.08

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Results 5

Irritation parameter:

erythema score

Remarks:

10% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.92

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Results 6

Irritation parameter:

edema score

Remarks:

10% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed in any animal at all time points

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

erythema score

Remarks:

5% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.415

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Results 8

Irritation parameter:

edema score

Remarks:

5% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed in any animal at any time point

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

erythema score

Remarks:

1% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0.92

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of weak irritation

Results 10

Irritation parameter:

edema score

Remarks:

1% test substance

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed in any animal at any time point

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

erythema score

Remarks:

vehicle control

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours (weak erythema in 1 animal 1 hour post-exposure)

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema in any animal at any time point

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

In general slight to well defined erythema was observed 1 to 72 hours after termination of exposure of 100% and 20% concentration of test article. Similarily in general slight erythema was observed 1 to 72 hours alter termination of exposure of 10%, 5% and 1% concentration of test article. Slight oedema was only observed in 1 rabbit 48 hours after termination of exposure of 100% and 20% concentration of test article. Thereafter no oedema was observed.
On day 7 and 14 dose related accumulations of scales were observed in all rabbits. On day 14 the skin of all rabbits was intact.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In the GLP-compliant guideline study, the test substance oxacyclohexadecan-2-one was not irritating to rabbit skin.

Executive summary:

In a GLP-compliant OECD 404 guideline study, the test substance oxacyclohexadecan-2 -one was tested for skin irritation in 4 rabbits, as a neat substance, 20%, 10%, 5% and 1% solution. Each animal received in total 6 applications (5 tested concentrations and a vehicle control). The exposure was 4 hours under semi-occlusive conditions. In general slight to well defined erythema was observed 1 to 72 hours after termination of exposure of 100% and 20% concentration of test article. Similarily in general slight erythema was observed 1 to 72 hours alter termination of exposure of 10%, 5% and 1% concentration of test article. Slight oedema was only observed in 1 rabbit 48 hours after termination of exposure of 100% and 20% concentration of test article. Thereafter no oedema was observed. Based on the calculated scores (mean for erythema and oedema at 24/48/72 hours of 1.58 and 0.08, respectively) for the neat substance no classification of oxacyclohexadecan-2-one for skin irritation is warranted according to Regulation 1272/2008/EC.