Butanoic acid, 3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-indenyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 Nov 2001 - 08 Feb 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

441-420-8

EC Name:

-

Cas Number:

113889-23-9

Molecular formula:

C14H20O2

IUPAC Name:

tricyclo[5.2.1.0²,⁶]dec-3-en-8-yl butanoate; tricyclo[5.2.1.0²,⁶]dec-4-en-8-yl butanoate

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 - 18:00) and twelve hours darkness

IN-LIFE DATES: From: 14 November 2001 To: 28 November 2001

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

test substance was used as supplied

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL under a 2.5 x 2.5 cm cotton gauze patch.

VEHICLE
Not applicable.

Duration of treatment / exposure:

4 hours

Observation period:

14 days. Observations were made after: 1, 24, 48, 72 hours, and 7 and 14 days.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: on the back of each rabbit, on the shorn skin.
- % coverage: 2.5 x 2.5 cm
- Type of wrap if used: 2.5 x 2.5 cm cotton gauze patch that was secured in position with a strip of surgical adhesive tape. The trunk of each rabbit was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
- Time after start of exposure: 4 hours.

SCORING SYSTEM:
Evidence of primary irritation were scored according to the following scale:
Erythema and Eschar Formation
-No erythema 0
-Very slight erythema (barely perceptible) 1
-Well-defined erythema 2
-Moderate to severe erythema 3
-Severe erythema (beet reddness) to slight eschar formation (injuries in depth) 4

Oedema Formation
-No oedema 0
-Very slight oedema (barely perceptible) 1
-Slight oedema (edges of area well-defined by definite raising) 2
-Moderate oedema (raised approximately 1 millimeter) 3
-Severe erythema (raised more than 1 millimeter and extending beyond area of exposure 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1 and #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Very slight erythema was noted at all treated skin sites one hour after patch removal with well defined erythema at the 24-hour observation and very slight to well-defined erythema at the 48 and 72-hour observations.
Slight oedema was noted at one treated skin site and very slight oedema was noted at two treated skin sites at the 24-hour observation. Very slight oedema was noted at two treated skin sites at the 48 and 72-hour observations.

Other effects:

No other effects observed.

Any other information on results incl. tables

Individual scores for erythema and oedema.

Skin reaction	Observation time	Individual Scores – Rabbit Number and Sex
		64 Male	37 Male	4 Female
Erythema / Eschar formation	24 hours	2	2	2
	48 hours	1	2	1
	72 hours	1	2	1
Oedema formation	24 hours	1	2	1
	48 hours	0	1	1
	72 hours	0	1	1

Applicant's summary and conclusion

Interpretation of results:

other: Not irritant

Remarks:

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

Conclusions:

Cyclobutanate does not cause skin irritation, based on a skin irritation test according to OECD TG 404.

Executive summary:

Cyclobutanate was tested for skin irritation, according to OECD 404 guidelines and under GLP conditions, using New Zealand White rabbits. The back of each rabbit was treated by 4-hour semi-occluded application of 0.5 mL of Cyclobutanate followed by a 14 day observation period. Typical observation points were at 1, 24, 48, 72 hours and 7 and 14 days after the start of the application. Very slight erythema was noted at all treated skin sites one hour after patch removal with well defined erythema at the 24-hour observation and very slight to well-defined erythema at the 48 and 72-hour observations. Slight oedema was noted at one treated skin site and very slight oedema was noted at two treated skin sites at the 24-hour observation. Very slight oedema was noted at two treated skin sites at the 48 and 72-hour observations. It is concluded that Cyclobutanate is not considered to be irritant to rabbit skin under the experimental conditions described in this report.