4,8-Cyclododecadien-1-one

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06-03-2014 to 09-03-2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met.

Justification for type of information:

Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: July 2012; signature: November 2012

Test material

Test material information

Constituent 1

Reference substance name:

(3E,7E)-cyclododeca-3,7-dien-1-one; (4E,8Z)-cyclododeca-4,8-dien-1-one; (4Z,8E)-cyclododeca-4,8-dien-1-one

EC Number:

941-893-5

Cas Number:

15229-79-5

Molecular formula:

C12H18O

IUPAC Name:

(3E,7E)-cyclododeca-3,7-dien-1-one; (4E,8Z)-cyclododeca-4,8-dien-1-one; (4Z,8E)-cyclododeca-4,8-dien-1-one

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: Keep in the dark at 0 - 10 °C, under nitrogen
- Other: Colourless

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised Supplier
- Age at study initiation: 12 - 20 weeks
- Weight at study initiation: 2.76 - 2.93 kg
- Housing: Individually housed in suspended cages.
- Diet (e.g. ad libitum): certified rabbit diet ad libitum
- Water (e.g. ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: From: To: 06-03-2014 to 09-03-2014

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL
- Concentration (if solution): Test material was used as supplied.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours (initial observation); additional observations are made daily up to Days 7 and 14 to assess the reversibility of skin reactions (as appropriate).

Number of animals:

3 female

Details on study design:

TEST SITE
- Area of exposure: dorsal
- Type of wrap if used: semi-occlusive (2.5 cm x 2.5 cm cotton gauze patch secured with surgical adhesive tape)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): Immediately, 1 hour, 24 hours, 48 hours and 72 hours. Additional observations daily up to 7 or 14 days, as appropriate.

SCORING SYSTEM:
Erythema and Eschar Formation
No erythema _________________________________________________________________________0
Very slight erythema (barely perceptible) ________________________________________________1
Well-defined erythema ________________________________________________________________2
Moderate to severe erythema __________________________________________________________3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) ________________4

Oedema Formation
No oedema __________________________________________________________________________0
Very slight oedema (barely perceptible) _________________________________________________1
Slight oedema (edges of area well-defined by definite raising) _____________________________2
Moderate oedema (raised approximately 1 millimetre) ____________________________________3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) ___4
Any other skin reactions and clinical signs of toxicity, if present, were also recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Max. score:

6

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No evidence of skin irritation was noted (maximum score = 0 for erythema and edema) in n=3 females at all observation periods.

Other effects:

All females showed expected gain in body weight during the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the test item is not considered to be irritating.

Executive summary:

The study was performed to OECD TG 404 and to assess the primary skin irritancy potential of the test substance in accordance with GLP in New Zealand White rabbits. Following single 4-Hour, semi-occluded applications to the intact rabbit skin. 0.5 ml of the test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the clipped skin to assess the irritancy potential of the test item. The patch was secured in position with a strip of surgical adhesive tape. After 4 hours of exposure to the test substance, the patches were removed and individual dose sites were scored at approximately 1, 24, 48, and 72 hours. A single 4-Hour, semi occluded application of the test item to the intact skin of three rabbits produced no erythema or edema after patch removal in the observation period up to 72 hours . No corrosive effects were noted. Mean scores for following grading at 24, 48 and 72h were zero (score = 0) in erythema and eschar and in edema scoring criteria. Under the conditions of the study, the test item is not considered to be a skin irritant.