Methyl [1α,2β(Z)]-(±)-3-oxo-2-(pent-2-enyl)cyclopentaneacetate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 09 September and 16 September 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

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

Test material

Test material information

Constituent 1

Reference substance name:

Methyl [1α,2β(Z)]-(±)-3-oxo-2-(pent-2-enyl)cyclopentaneacetate

EC Number:

243-497-1

EC Name:

Methyl [1α,2β(Z)]-(±)-3-oxo-2-(pent-2-enyl)cyclopentaneacetate

Cas Number:

20073-13-6

Molecular formula:

C13H20O3

IUPAC Name:

methyl 2-[(1S,2S)-3-oxo-2-[(2Z)-pent-2-en-1-yl]cyclopentyl]acetate

Specific details on test material used for the study:

Sponsor's identification: JASMONEIGE (Lot No. 75028)
Lot number: 75028
Date received: 24 August 1999
Description: colourless liquid
Storage conditions: approximately 4° C in the dark under nitrogen

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand White rabbits supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK were used. At the start of the study the animals weighed 2.41 to 2.66 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK) was allowed throughout the study.
The temperature and relative humidity were controlled to remain within target ranges of 17 to 23 °C and 30 to 70% respectively. Occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 mL of test item

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3

Details on study design:

Procedure
On the day before the test each rabbit was clipped free of fur from the dorsal flank are using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

On the day of the test a suitable site was selected on the back of each rabbit. A quantity of 0.5 mL of the test material was introduced under a 2.5 cm x 2.5 cm cotton gause patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate sice 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in a an elasticated corset (TUBIGIP) and the animals were returned to their cages for the duration of the exposure period.

Four hours after application the corest and patches were removeed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in 74 % Industrial Methylated Spirits.

Approximate one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritaion and scored according to the following scale:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value
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 Value
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite 2
raising)
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, if present, were also recorded.
An additional observation was made on Days 7 to assess the reversibility of skin reactions.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

Very slight erythema was noted at all treated skin sites one hour after patch removal. Well defined erythema was noted at two treated skin sites with very slight erythema at the remaining treated skin site at the 24 hour observation. Well defined erythema persisted at one treated skin site with very slight erythema at two treated skin site with very sligth erythema at two treated skin sites at the 48 hours observation. very slight erythema was noted at one treated skin site at the 72 hours observation.

Very slight oedema was noted at all treated skin sites at the 24 hours observation and persisted at one treated skin site at the 48 hour observation.

Two treated skin sites appeared normal at the 72 hour observations and the remaining treated skin site appeared normal at the 7 day observation.

Any other information on results incl. tables

Individual daily and mean scores for dermal irritation following 4 hour exposure

Skin Reaction	Reading (Hours)	Individual Scores - Rabbit Number and Sex (Bodyweight kg)
		35 Male (2.41)	36 Male (2.45)	38 Male (2.66)
Erythema/Eschar Formation	24	1	2	2
	48	1	1	2
	72	0	0	1
Total		2	3	5
Mean Score		0.7	1.0	1.7
Oedema Formation	24	1	1	1
	48	0	0	1
	72	0	0	0
Total		0	1	2
Mean Score		0.	0.3	0.7

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test materials did not meet the criteria for classification as irritant or corrosive according to CLP.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adpoted 17 July 1992) and Methods B4 of Commission Directive 92/69/EEC.

A single 4 hours, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well defined erythema and very slight oedema. Two treated skin sites appeared normal at th 72 hours observation and the remaining treate skin site appeared normal at the 7 day observation.

The test material did not meet the criteria for classification as irritant or corrosive according to CLP.