Exo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl propionate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Apr 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

This information is used for read across to Isobornyl propionate.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

4 chemicals were assessed simultaneously per animal, at distant and well defined sites

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: methods for determination of toxicity (Annex V of the EEC Directive 79/831)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Exo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl acetate

EC Number:

204-727-6

EC Name:

Exo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl acetate

Cas Number:

125-12-2

Molecular formula:

C12H20O2

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: A. Smith, 7 Kydcomb Road, Warlingham, Surry
- Housing: Individual in aluminium cages with grid floors and no bedding material.
- Diet: Commercially available pelleted rabbit diet (product ref. 680, Dalgety-Spillers Limited)
- Water: Mains tap water was available at all times via automatic drinking nozzles in each cage
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 22
- Humidity (%): 42 to 65
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

168 hours (7 days)

Number of animals:

4 females

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm square on the clipped dorsal skin
- Type of wrap: The test material was placed evenly over a square (2.5 cm) of surgical lint B.P. The lint square was then placed onto the animal’s skin. The lint patches were held in place by encircling the trunk of the animal with a length of ‘Elastoplast’ elastic adhesive bandage (10 cm wide)

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: The patch was removed after 4 hours.
- Washing: the treated sites were cleansed by gentle swabbing with cotton wool soaked in warm water.

OBSERVATION TIME POINTS
1, 24, 78 and 168 hours after removal of the test substance

SCORING SYSTEM
- Erythema and Eschar formation: 0 (no erythema); 1 (very slight erythema (barely perceptible); 2 (well-defined erythema); 3 (moderate to severe erythema); 4 (severe erythema (beet redness) to slight eschar formation (injuries in depth)
- Oedema formation: 0 (no oedema); 1 (very slight oedema (barely perceptible); 2 (slight oedema (edges of area well defined by definite raising); 3 (moderate oedema (raised approximately 1 mm); 4 (severe oedema (raised more than 1 mm and extending beyond area of exposure)
- Other signs of reaction to treatment such as corrosive action or systemic effects were fully described.
- Method of calculation: The numerical values or scores given to the erythema observed in each animal of the treated group at the twenty four, forty eight and seventy two hour examinations were summed. This total was then divided by three, the number of examinations that the figures were taken from, and further divided by the number of animals in the group. The value obtained on assessing oedematous reaction were similarly treated. The average scores obtained may be used in any subsequent classification of the material, a value of two or more for either erythema or oedema resulting in the material being regarded as irritant to the skin.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 168 hours

Results 2

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 168 hours

Results 3

Irritation parameter:

edema score

Basis:

animal: #1 and #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 168 hours

Results 4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 168 hours

Results 5

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 168 hours

Irritant / corrosive response data:

- One hour after dosing: well defined erythema and slight oedema were observed in two animals, well defined erythema and very slight oedema were observed in one animal and very slight erythema and oedema of the treated skin were noted in the remaining animal. The response of this animal slightly increased within 24 hours of dosing when well defined erythema and slight oedema were apparent. This reaction had reversed back to that previously described within 72 hours of dosing.
- 168 hours after dosing: Well defined erythema and very slight oedema of the skin were observed in two rabbits at the 168 hour observation, one other animal of the group exhibiting very slight erythema and oedema.

Other effects:

- Other adverse local effects: At the 168 hour timepoint slight desquamation was observed in animal #1 and #2, desquamation was observed in animal #4. No such signs were apparent in animal #3.

Any other information on results incl. tables

Summary of data

	Erythema				edema
Time	Animal #1	Animal #2	Animal #3	Animal #4	Animal #1	Animal #2	Animal #3	Animal #4	Comments
1 hour	2	2	2	1	2	2	1	1	None
24 hours	2	2	2	2	2	2	1	2	None
48 hours	2	2	2	2	2	2	1	1	None
72 hours	2	2	2	1	2	2	1	1	None
168 hours	2	2	1	0	1	1	1	0	Slight desquamation in animals #1 and 2, desquamation in animal #4
Average/animal (1 and 168 hours not included)	2	2	2	1.7	2	2	1	1.3
Average/overall	1.9				1.6

Applicant's summary and conclusion

Interpretation of results:

other: Not a skin irritant

Remarks:

in accordance with EU CLP (EC No. 1272/2008 and its updates)

Conclusions:

Based on the mild irritating properties of the substance observed in the presented study in rabbit, the substance is not classified as irritating to the skin.

Executive summary:

A GLP-compliant skin irritation study was performed similar to OECD TG 404. Four Female New Zealand White rabbits were treated with 0.5 mL unchanged test substance on the clipped dorsal skin (applied on 2.5 cm²surgical lint). The material was applied simultaneously with 3 other substances on distant sites. The material was held in contact with the skin using a semi-occlusive patch assembly for 4 hours after witch the patches were removed and the skin was cleaned with cotton wool soaked in warm water. Examinations for sign of reaction to the treatment were made after 1, 24, 48, 72 and 168 hours. One hour after dosing well defined erythema and slight edema were observed in two animals, well defined erythema and very slight edema were observed in one animal and very slight erythema and edema of the treated skin were noted in the remaining animal. The response of this animal slightly increased within 24 hours of dosing when well defined erythema and slight edema were apparent. This reaction had reversed back to that previously described within 72 hours of dosing. Well defined erythema and very slight edema of the skin were observed in two rabbits at the 168 hour observation, one other animal of the group exhibiting very slight erythema and edema. Desquamation from the skin surface was also observed in three rabbits. The average scores calculated from the numerical values given to the irritation observed at the 24, 48 and 72 hour observations were 1.9 for erythema and 1.6 for edema.