[No public or meaningful name is available]

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25-11-2003 to 02-12-2003

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:

2004

Report date:

2004

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: December 2002 ; signature: February 2003

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

451-230-7

EC Name:

-

Cas Number:

55739-89-4

Molecular formula:

C10H18O

IUPAC Name:

2-ethyl-4,4-dimethylcyclohexan-1-one

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: approximately 4 ºC in the dark, under nitrogen
- Other: clear 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 to 20 weeks
- Weight at study initiation: 2.0 to 3.5 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: 12-11-2003 To: 02-12-2003

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration (if solution): Used as supplied (liquid)

VEHICLE
- Amount applied: Not applicable.

Duration of treatment / exposure:

4 hours - 3 males

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): 3 males: Immediately, 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

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0.9

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

n = 3

Time point:

24/48/72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 8

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Very slight erythema (score = 1) was noted at all treated sites one hour after patch removal and at the 24 and 48-hour observations and persisted at two treated skin sites at the 72-hour observation. Very slight oedema (score = 1) was noted at two treated sites at the 24-hour observation. All sites were normal at the 7 day observation period.

Any other information on results incl. tables

Table 1. Individual Scores and Mean Scores following 4-hour exposure

Skin Reaction	Reading (hours)	1# Male	#2 Male	3# Male
Erythema/Escar Formation	24	1	1	1
	48	1	1	1
	72	1 Le	1	0
	Total	3.0	3.0	2.0
	Mean	1.0	1.0	0.7
Oedema Formation	24	1	0	1
	48	0	0	0
	72	0	0	0
	Total	1.0	0.0	1.0
	Mean	0.3	0.0	0.3

 * Le : loss of elasticity

Note: All effects reversed by day 7 (score = 0.0)

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

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 item in accordance with GLP in New Zealand White rabbits. The test item was applied sequentially. Initially, one male for 3-minute, 1-hour and 4-hour 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. 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. Very slight erythema (score = 1) was noted at all treated sites one hour after patch removal and at the 24 and 48-hour observations and persisted at two treated skin sites at the 72-hour observation. Very slight oedema (score = 1) was noted at two treated sites at the 24-hour observation. Loss of skin elasticity was noted at one site. One treated site was normal at 72 hours. All sites were normal at the 7 day observation period. No corrosive effects were noted. Mean scores following grading at 24, 48 and 72h were score 1.0/1.0/0.7 in erythema and eschar and score 0.3/0.0/0.3 in oedema scoring criteria, respectively. Under the conditions of the study, the test item is not considered to be a skin irritant.