3-(4,4-dimethylcyclohex-1-en-1-yl)propanal

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23-03-2010 to 30-06-2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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: September 2009 ; signature: November 2009

Test material

Test material information

Constituent 1

Reference substance name:

3-(4,4-dimethylcyclohex-1-en-1-yl)propanal

EC Number:

700-339-0

Cas Number:

850997-10-3

Molecular formula:

C11H18O

IUPAC Name:

3-(4,4-dimethylcyclohex-1-en-1-yl)propanal

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: Refrigerator (between 0 and 10ºC 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 (documented in the full study report)
- Age at study initiation: 12 to 20 weeks
- Weight at study initiation: 2.19 to 2.22 kg
- Housing: Individually housed in suspended cages.
- Diet (ad libitum): Certified Rabbit diet (recognised supplier); provided ad libitum
- Water (ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

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

IN-LIFE DATES: From: 23-03-2010 To: 06-04-2010

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration (if solution): Not applicable.

VEHICLE
- Amount applied: Not applicable.

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 males

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. Earlier if appropriate based on observations.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 1 hour, 4 hours, 24 hours, 48 hours and 72 hours. Additional observations daily up to 7 or 14 days, as appropriate

SCORING SYSTEM: Draize Scale:
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

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: Slight desquamation at day 14

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks:

Slight desquamation at day 14

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks:

Slight desquamation at day 14

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Well-defined erythema (score =2) and slight oedema (score = 2) were noted at both (n=2) treated skin sites at the 24, 48 and 72-Hour observations. Other skin reactions noted at both treated skin sites at the 48 and 72-Hour observations were light brown discolouration of the epidermis and loss of skin flexibility and/or elasticity. Crust formation, prevented accurate evaluation of erythema and oedema, was noted at both treated skin sites at the 7-Day observation. Slight desquamation was noted at both treated skin sites at the 14-Day observation.

Other effects:

- Other adverse local effects: None reported.
- Other adverse systemic effects: None reported. Individual bodyweights increased during the conduct of the study period.

Any other information on results incl. tables

Table 1. Individual skin reactions

Skin Reaction	Observation Time	Individual Scores
		1 (male)	2 (male)	3 (-)
Erythema/Eschar formation	1 hour	0	0	-
	24 hours	2	2	-
	48 hours	2 BrLe	2 BrLe	-
	72 hours	2 BrLeLf	2 BrLeLf	-
	7 days	#e Cf	#e Cf	-
	14 days	0 D	0 D	-
Oedema formation	1 hour	0	0	-
	24 hours	2	2	-
	48 hours	2	2	-
	72 hours	2	2	-
	7 days	#od	#od	-
	14 days	0	0	-

Br = Light brown discoloration of the epidermis

Le = Loss of skin elasticity

Lf = Loss of skin flexibility

Cf = Crust formation

D = Slight desquamation

#e = adverse reaction prevented accurate evaluation of erythema

#od = adverse reaction prevented accurate evaluation of oedema

- = observation not performed or observation not required

 

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

Erythemea/Escar Formation:

1: total = 6 ; mean score = 2.0 (and slight desquamation at day 14)

2: total = 6 ; mean score = 2.0 (and slight desquamation at day 14)

3: total = - ; mean score = - (score -)

Oedema Formation:

1: total = 0 ; mean score = 2.0 (reversed at day 14)

2. total = 5 ; mean score = 2.0 (reversed at day 14)

3: total = - ; mean score = - (score -)

 

Note: Crust formation, prevented accurate evaluation of erythema and oedema, was noted at both treated skin sites at the 7-Day observation. Slight desquamation was noted at both treated skin sites at the 14-Day observation.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test item is 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 item in New Zealand White rabbits in accordance with GLP. The test item was applied to two males f by semi-occluded application to the intact rabbit skin with 0.5 mL test item introduced under a 2.5 cm x 2.5 cm cotton gauze patch on the clipped skin or 4-hours. The patch was secured in position with a strip of surgical adhesive tape. After exposure to the test item, the patches were removed and individual dose sites were scored at approximately 1, 24, 48, and 72 hours. No corrosive effects were noted. Well-defined erythema (score =2) and slight oedema (score = 2) were noted at both (n=2) treated skin sites at the 24, 48 and 72-Hour observations. Other skin reactions noted at both treated skin sites at the 48 and 72-Hour observations were light brown discolouration of the epidermis and loss of skin flexibility and/or elasticity. Crust formation, prevented accurate evaluation of erythema and oedema, was noted at both treated skin sites at the 7-Day observation. Mean scores following grading at 24, 48 and 72h were score 2.0/2.0 in erythema and eschar and score 2.0/2.0 in oedema scoring criteria, respectively. Slight desquamation was noted at both treated skin sites at the 14-Day observation. Under the conditions of the study, the test item is considered to be a skin irritant. Applicant assessment indicates: that the CLP Regulation (EC) 1272/2008 Skin Irritation : category 2 classification within the inflammation criteria (erythema/eschar and oedema) being mean score at 24, 48 and 72 h > or = 2.3 in two (of three potential) sites was not met. The study was originally classified under DSD 67/548/EEC which utilised a mean score of 2.0 for positive result. The study was terminated on day 14 under DSD 67/548/EEC, all erythema/eschar and oedema inflammation had ceased although ‘slight desquamation’ persisted in two (of three potential) sites to day 14. Therefore, CLP Regulation (EC) 1272/2008 : Skin Irritant Category 2 classification is maintained.