Reaction mass of (3E)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butan-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)butan-2-one

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

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:

Reaction mass of (3E)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butan-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)butan-2-one

EC Number:

700-956-5

Molecular formula:

not applicable (reaction mass of constitutional isomers)

IUPAC Name:

Reaction mass of (3E)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butan-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)butan-2-one

Test material form:

gas under pressure: refrigerated liquefied gas

Details on test material:

- Physical state: liquid
- Storage condition of test material: Approximately 4 °C in the dark, under nitrogen.
- Other: Pale yellow

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: recognised animal supplier
- Age at study initiation: 12 - 20 weeks
- Weight at study initiation: 2.37 - 2.75 kg
- Housing: Individually housed in suspended cages.
- Diet: certified rabbit diet ad libitum
- Water: mains drinking water ad libitum
- Acclimation period: at least 5 days

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

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

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

Number of animals:

3

Details on study design:

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

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, only within sentinel rabbit used in preliminary test. Three patches applied. One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test item was removed by gentle swabbing with cotton wool soaked in distilled water.
In the definitive test for skin irritation (after consideration of the sentinel skin reactions) with two additional rabbits; no washing/swabbing of the test site was reported after 4 hours application and removal of the patch.
- Time after start of exposure: 4 hours

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:

erythema score

Basis:

mean

Remarks:

(n=3)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

(n=3)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(n=3)

Time point:

other: 24h

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Results 4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(n=3)

Time point:

other: 48h

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Results 5

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(n=3)

Time point:

other: 72h

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Results 6

Irritation parameter:

edema score

Basis:

mean

Remarks:

(n=3)

Time point:

other: 24h

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Results 7

Irritation parameter:

edema score

Basis:

mean

Remarks:

(n=3)

Time point:

other: 48h

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Results 8

Irritation parameter:

edema score

Basis:

mean

Remarks:

(n=3)

Time point:

other: 72h

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Irritant / corrosive response data:

- Erythema: No evidence of skin irritation was noted during the study.
- Edema: No evidence of skin irritation was noted during the study.
- Reversibility of effects: Not applicable.

Other effects:

- Other adverse local effects: None
- Other adverse systemic effects: No signs of systemic toxicity were noted during the observation period. All animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Table 1. Individual skin reactions

Skin Reaction	Observation Time	Individual Scores
		1 (male)	2 (male)	3 (male)
Erythema/Eschar formation	1 hour	0	0	0
	24 hours	0	0	0
	48 hours	0	0	0
	72 hours	0	0	0
Edema formation	1 hour	0	0	0
	24 hours	0	0	0
	48 hours	0	0	0
	72 hours	0	0	0

 

Mean scores per organism at 24, 48 and 72h:

Erythemea/Escar Formation:

1: total = 0; mean score = 0

2: total = 0; mean score = 0

3: total = 0; mean score = 0

Edema Formation:

1: total = 0; mean score = 0

2. total = 0; mean score = 0

3. total = 0; mean score = 0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

EU criteria not met

Conclusions:

Under the conditions of this study the substance is not irritating to the skin.

Executive summary:

The study was performed to OECD TG 404 and EU Method B.4 in accordance with GLP to assess the primary skin irritancy potential of the test item in New Zealand White rabbits to assess the irritancy potential of the test item following single, 3-Minute, 1 and 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. The patch was secured in position with a strip of surgical adhesive tape. 3-Minute and 1-Hour semi-occluded applications of the test item to the intact skin of one rabbit produced no evidence of skin irritation. After 4 hours of exposure to the test substance, the patches were removed and individual dose sites were scored according to the Draize scoring system 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 evidence of skin irritation. Mean scores for following grading at 24, 48 and 72h were zero in both scoring criteria and there was no other signs or systemic toxicity noted during the study. Under the conditions of the study, the substance cannot be considered a skin irritant.