A mixture of: 4-(2,2,3-trimethylcyclopent-3-en-1-yl)-1-methyl-2-oxabicyclo[2.2.2]octane; 1-(2,2,3-trimethylcyclopent-3-en-1-yl)-5-methyl-6-oxabicyclo[3.2.1]octane; spiro[cyclohex-3-en-1-yl-[(4,5,6,6a-tetrahydro-3,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]furan]; spiro[cyclohex-3-en-1-yl-[4,5,6,6a-tetrahydro-4,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]]furan]

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 14 April 1993 and 26 April 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: 4-(2,2,3-trimethylcyclopent-3-en-1-yl)-1-methyl-2-oxabicyclo[2.2.2]octane; 1-(2,2,3-trimethylcyclopent-3-en-1-yl)-5-methyl-6-oxabicyclo[3.2.1]octane; spiro[cyclohex-3-en-1-yl-[(4,5,6,6a-tetrahydro-3,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]furan]; spiro[cyclohex-3-en-1-yl-[4,5,6,6a-tetrahydro-4,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]]furan]

EC Number:

422-040-1

EC Name:

A mixture of: 4-(2,2,3-trimethylcyclopent-3-en-1-yl)-1-methyl-2-oxabicyclo[2.2.2]octane; 1-(2,2,3-trimethylcyclopent-3-en-1-yl)-5-methyl-6-oxabicyclo[3.2.1]octane; spiro[cyclohex-3-en-1-yl-[(4,5,6,6a-tetrahydro-3,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]furan]; spiro[cyclohex-3-en-1-yl-[4,5,6,6a-tetrahydro-4,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]]furan]

Cas Number:

426218-78-2

Molecular formula:

C16H26O

IUPAC Name:

1-methyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)-2-oxabicyclo[2.2.2]octane; 3,6',6',6'a-tetramethyl-2',3'a,4',5',6',6'a-hexahydrospiro[cyclohexane-1,3'-cyclopenta[b]fura]-3-ene; 4,6',6',6'a-tetramethyl-2',3'a,4',5',6',6'a-hexahydrospiro[cyclohexane-1,3'-cyclopenta[b]fura]-3-ene; 5-methyl-1-(2,2,3-trimethylcyclopent-3-en-1-yl)-6-oxabicyclo[3.2.1]octane

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three healthy adult rabbits of the New Zealand White strain were obtained from Rosemead.
They were in the weight range of 2.4 to 3.1 kg and approximately 11 to 13 weeks of age, prior to treatment (Day 1). All rabbits were acclimatised to the experimental environment.
The rabbits were selected without conscious bias for the study. They were housed individually in metal cages with perforated floors in Building R14 Room 5.
A standard laboratory diet SDS Stanrab (P) Rabbit Diet and drinking water were provided ad libitum.
The batch of diet used for the study was not analysed for nutrients, contaminants or micro-organisms.
Results of routine chemical examination of drinking water at source as conducted usually weekly by the supplier, are made available to Huntingdon Research Centre Ltd. as quarterly summaries.
Animal room temperature was maintained at approximately 19°C and relative humidity at 30 - 70% .
These environmental parameters were recorded daily. Air exchange was maintained at approximately 19 air changes per hour and lighting was controlled by means of a time switch to give 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.
Each animal was identified by a numbered aluminium tag placed through the edge of one ear. This number was unique within the HRC Industrial Toxicology Department throughout the duration of the study. Each cage was identified by a coloured label displaying the study schedule number, animal
number and initials of the Study Director and Home Office licensee.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

A 0.5 ml amount of the test substance was applied under a 25 mm x 25 mm gauze pad to one intact skin site on each animal.

Duration of treatment / exposure:

4 hours

Observation period:

13 days

Number of animals:

3

Details on study design:

TEST SUBSTANCE PREPARATION:
The substance was administered, as supplied by the Sponsor. The absorption of the substance was not determined. The homogeneity, stability and purity of the substance were the responsibility of the Sponsor.

TREATMENT PROCEDURE
Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 100 mm x 100 mm.
A 0.5 ml amount of the test substance was applied under a 25 mm x 25 mm gauze pad to one intact skin site on each animal.
Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment.
At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with warm water (30° to 40°C) to remove any residual test substance . The treated area was blotted dry with absorbent paper.

OBSERVATIONS
Clinical signs: All animals were observed daily for signs of ill health or toxicity .
Dermal responses: Examination of the treated skin was made on Day 1 (i.e . approximately 30 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure) .
Additional observations were made on Days 5 through 13.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 1824 female

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 9 days

Remarks on result:

other: Desquamation of the stratum corneum at days 5 to 8

Results 2

Irritation parameter:

erythema score

Basis:

animal: 1825 female

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 13 days

Remarks on result:

other: Blanching at days 2 to 5, necrosis at days 6 to 8, small scabs at day 9, desquamation of the stratum corneum at days 10 to 12

Results 3

Irritation parameter:

erythema score

Basis:

animal: 1826 female

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: Desquamation of the stratum corneum at day 5

Results 4

Irritation parameter:

edema score

Basis:

animal: 1824 female

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Results 5

Irritation parameter:

edema score

Basis:

animal: 1825 female

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 13 days

Remarks on result:

other: necrosis at day 3 and small scabs at days 10 to 12

Results 6

Irritation parameter:

edema score

Basis:

animal: 1826 female

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritant / corrosive response data:

The numerical values given to the dermal reactions elicited by the substance are presented in the result section. Very slight to well-defined erythema with very slight to slight oedema was seen in all three animals following removal of the dressings. These reactions increased in severity, and well-defined to severe erythema with blanching and/or necrosis and very slight to moderate oedema was observed. The reactions gradually ameliorated and had resolved completely by Day 6, 9 or 13.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Applicant's summary and conclusion

Interpretation of results:

other: Skin irritant

Remarks:

in accordance with EU CLP (EC no 1272/2008 and its amendments)

Conclusions:

The substance causes skin irritation in the in vivo acute dermal irritation test (OECD guideline 404).

Executive summary:

The substance has been tested in an in vivo acute dermal irritation test (OECD TG 404). An amount of 0.5 mL was applied in a semiocclusive manner to the clipped skin of 3 New Zealand White female rabbits. Exposure time was 4 hours after which skin reactions were observed for 13 days. Very slight to well-defined erythema with very slight to slight oedema was seen in all three animals following removal of the dressings. These reactions increased in severity, and well-defined to severe erythema with blanching and/or necrosis and very slight to moderate oedema was observed. The reactions gradually ameliorated and had resolved completely by Day 6, 9 or 13. Average scores over the observation period were 2, 2 and 4 for erythema and 2, 3 and 1 for oedema. There were no signs of toxicity or ill health in any rabbit during the observation period. Based on these results, the substance causes skin irritation.