Ethyl trans-2,2,6-trimethylcyclohexanecarboxylate

Endpoint summary

Description of key information

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". 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. No corrosive effects were noted.

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion". A single instillation of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. No corneal or iridial effects were noted during the study. Minimal conjunctival irritation was noted in all treated eyes one hour after treatment. All treated eyes appeared normal 24 hours after treatment. The test material does not require to be classified according to the CLP criteria.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

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.

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.

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

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

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

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)

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

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 January 1993 to 24 January 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues 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 2.70 - 3.12 kg and were approximately 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 a 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 18 - 22°C and relative humidity of 46-65%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 mL

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope.Animals showing evidence of ocular lesions were rejected and replaced.One rabbit was initially treated . A volume of 0.1 mL of the test material was instilled in to the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eye ball. The upper and lower eye lids were held together for about one second immediately after instillation, to prevent loss of the test material , and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made.
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Assessment of ocular damage / irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation from Draize J.H. 1959, Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals i n Foods, Drugs and Cosmetics".
Any other ocular effects were also noted. Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Time point:

other: 1h

Score:

0

Max. score:

1

Remarks on result:

other: Max. duration: 1 h; Max. value at end of observation period: 0 (related to all animals)

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1h

Score:

0

Max. score:

1

Remarks on result:

other: Max. duration: 1 h; Max. value at end of observation period: 0 (related to all animals)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1h

Score:

0

Max. score:

0

Remarks on result:

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

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1h

Score:

0

Max. score:

0

Remarks on result:

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

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study.
Minimal conjunctival irritation was noted in all treated eyes one hour after treatment.
All treated eyes appeared normal 24 hours after treatment.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material does not require to be classified according to the CLP criteria.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion" referenced as Method B5 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

A single instillation of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation.

No corneal or iridial effects were noted during the study.

Minimal conjunctival irritation was noted in all treated eyes one hour after treatment.

All treated eyes appeared normal 24 hours after treatment.

The test material does not require to be classified according to the CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results of the in vivo skin irritation study, the substance is classified as a Skin Irritant Category 2 in accordance with the CLP Regulation.

Classification as an eye irritant is not required based on the results of an in vivo eye irritation study.