Ethyl trans-2,2,6-trimethylcyclohexanecarboxylate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 December 1992 to 29 December 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl trans-2,2,6-trimethylcyclohexanecarboxylate

EC Number:

412-540-8

EC Name:

Ethyl trans-2,2,6-trimethylcyclohexanecarboxylate

Cas Number:

22471-55-2

Molecular formula:

C12 H22 O2

IUPAC Name:

ethyl trans-2,2,6-trimethylcyclohexanecarboxylate

Constituent 2

Reference substance name:

Ethyl cis-2,2,6-trimethylcyclohexane-1-carboxylate

Molecular formula:

C12H22O2

IUPAC Name:

Ethyl cis-2,2,6-trimethylcyclohexane-1-carboxylate

impurity 1

Reference substance name:

Unidentified impurities

Molecular formula:

Not specified.

IUPAC Name:

Unidentified impurities

Test material form:

liquid: viscous

Details on test material:

Test material identification : ET-344 SP
Chemical name : Ethyl 2,2,6-trimethyl cyclohexanecarboxylate
Description: Clear, colourless liquid
Date received: 2 November 1992
Container: Metal bottle x3
Storage conditions: Room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Specification
Three New Zealand White rabbits were supplied by David Percival Ltd., Moston, Sandbach, Cheshire, U.K. At the start of the study the animals weighed 2.55 - 2.65 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.
Husbandry
The animals were individually housed in suspended metal cages.Free access to mains drinking water and food (RABMA Rabbit Diet, Special Diet Services Ltd., Witham, Essex, U.K.) was allowed throughout the study.The animal room was maintained at a temperature o f 17 - 19°C and relative humidity o f 46 - 52%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give continuous 12 hours light and 12 hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

3 days

Number of animals:

3

Details on study design:

On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal flank area 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 test 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 gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm X 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration o f the exposure period.Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether.Approximately one hour following the removal of the patches, and 24,48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J.H.(1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics".Any other skin reactions, if present, were also recorded.An additional observation was made on day 7 to assess the reversibility of skin reactions.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Max. duration: 7 d; Max. value at end of observation period: 0 (related to all animals)

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

7 d

Score:

4

Max. score:

4

Remarks on result:

other: Max. duration: 7 d; Max. value at end of observation period: 0 (related to all animals)

Irritant / corrosive response data:

No corrosive effects were noted.
Reversibility of any observed effect: Changes fully reversible within 7 days.

Other effects:

Well-defined erythema was noted at all treated skin sites one hour after patch removal with very slight to well-defined erythema at the 24 and 48-hour observations and well-defined erythema at the 72-hour observation.
Slight to severe oedema was noted at all treated skin sites one and 24 hours after patch removal with slight to moderate oedema at the 48 and 72-hour observations. Oedema extending ventrally below the treatment site was noted at two treated skin sites during this time.
The erythema and oedema extended up to 3 cm beyond all treated skin sites during the study.
Desquamation was noted at all treated skin sites seven days after treatment.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test material was classified as an irritant to skin (category 2) according to criteria of the CLP regulation.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation / Corrosion" referenced as Method B4 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and slight to severe oedema. Desquamation was noted at all treated skin sites seven days after treatment.

The test material was classified as an irritant to skin according to criteria of the CLP regulation.

No corrosive effects were noted.