4-Cyclopentadecen-1-one, (4Z)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1991-07-09 to 1991-07-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

age of animals at study initiation not reported

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

age of animals at study initiation not reported

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 19 June 1990. Signed on 5 October 1990.

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-900-5

EC Name:

-

IUPAC Name:

429-900-5

Test material form:

liquid

Details on test material:

- Physical state: colourless liquid
- Storage condition of test material: in the dark at about 4°C

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex.
- Age at study initiation: no data
- Weight at study initiation: 2.6-3.0 kg
- Housing: individually in grid bottomed metal cages.
- Diet (e.g. ad libitum): antibiotic free rabbit diet ad libitum (SQC standard rabbits pellets, produced by Special Diets Services, Witham, Essex)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C. On 3 occasions the temperature exceeded this range by 1°C.
- Humidity (%): 59-69 % with the exception of one occasion when a value of 76 % relative humidity was recorded.
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, and 72 hours after patch removal. Additional examination on day 7.

Number of animals:

4 animals

Details on study design:

TEST SITE
- Area of exposure: dorsal surface of the trunk
- % coverage: 2.5 cm square (6.25 cm2)
- Type of wrap if used: surgical lint held in position with "Elastoplast" elastic adhesive bandage 7.5 cm wide.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton wool soaked in warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scale according to OECD guideline No. 404

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

One hour after the end of the dosing period, erythema varying in degree from slight to well defined was apparent in all 4 rabbits and very slight oedema was noted in 2 of the 4 animals.
24 hours after patch removal erythema and oedema were observed in all 4 rabbits.
At the 72 hour assessment, irritation has entirely subsided in 2 animals. Erythema was slight to moderate in the remaining 2 rabbits.
7 days after the dosing, erythema and oedema were no longer apparent in any of the animal although skin thickening was noted in one of them.

Other effects:

none

Any other information on results incl. tables

Table 7.3.1/1: Mean irritant/corrosive response data (4 animals) at each observation time up to removal of animals from the test

 

Score at time point / Reversibility	Erythema Max. score 4	Edema Max. score 4
1 h	1.75	0.5
24 h	1.25	1.25
48 h	1.50	0.75
72 h	1.50	0.75
Average 24h, 48h, 72h	1.4	0.9
Reversibility*)	c	c
Average time (day) for reversion**	7 days	7 days

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which skin irritation signs in the last animal were observed

Table 7.3.1/2: Irritant/corrosive response data for each animal at each observation time up to removal of animals from the test

Score at time point / Reversibility	Erythema Max. score 4	Oedema Max. score 4
24 h	1 / 1 / 1 / 2	2 / 1 / 1 / 1
48 h	2 / 1 / 0 / 3	1 / 1 / 0 / 1
72 h	3 / 0 / 0 / 3	1 / 0 / 0 / 2
Average 24h, 48h and 72h	2 / 0.66 / 0.33 / 2.66	1.33 / 0.66 / 0.33 / 1.33
Reversibility*)	c	c
Average time for reversion	7 days	7 days

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

Under the test conditions, since a slight irritation being completely reversible within 7 days was observed:
- no additional self-classification is proposed for the registered substance regarding skin irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP)
- the registered substance is classified as Category 3 (slight skin irritation) according to the GHS based on differences betwen the individual scores for each animal within 3 scoring times (24, 48 and 72 h) for erythema (2 / 0.66 / 0.33 / 2.66).

Executive summary:

In a dermal irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.5 mL of undiluted test material was dermally applied on the shaved skin of the dorsal surface of the trunk of 4 New Zealand White rabbits.Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for up to 7 days for edema and erythema. 

Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hrs after the removal of the patch and on day 7.

The individual scores for each animal within 3 scoring times (24, 48h and 72 hours) were 2 / 0.66 / 0.33 / 2.66 for erythema and 1.33 / 0.66 / 0.33 / 1.33 for oedema.

Under the test conditions, since a slight irritation being completely reversible within 7 days was observed:

- no additional self-classification is proposed for the registered substance regarding skin irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP)

- the registered substance is classified as Category 3 (slight skin irritation) according to the GHS based on differences betwen the individual scores for each animal within 3 scoring times (24, 48 and 72 h) for erythema (2 / 0.66 / 0.33 / 2.66).

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.