Anisole

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 31/05/1994 to 20/07/1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. The purity of the test substance is not indicated.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Anisole

EC Number:

202-876-1

EC Name:

Anisole

Cas Number:

100-66-3

Molecular formula:

C7H8O

IUPAC Name:

anisole

Test material form:

other: colourless liquid, stored at room temperature

Details on test material:

- Name of test material (as cited in study report): Anisole
- Physical state: liquid
- Stability under test conditions: no data
- Storage condition of test material: at room temperature
- Other: The pH of the test substance was irrelevant.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
- Age at study initiation: no data
- Weight at study initiation: 2.7 +/- 0.1 kg
- Housing: individually in polystyrene cages (35 x 55 x 32 cm or 48.2 x 58 x 36.5 cm)
- Diet (e.g. ad libitum): 112 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12hrs dark/ 12 hrs light

IN-LIFE DATES: From: To: no data

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

the test item is used as supplied by the sponsor (undiluted)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): not applicable

VEHICLE: not applicable

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after removal of the dressing and then daily until day 15.

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: right flank (6 cm2)
- % coverage: no data
- Type of wrap if used: the test item was applied to a 6 cm2 dry hydrophilic gauze patch and this was then applied to the right flank of the animals.
The test substance and the gauze patch were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none. Any residual test substance was observed.
- Time after start of exposure: not applicable

SCORING SYSTEM: OECD recommended scoring system.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.9

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 7

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 8

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 9

Irritation parameter:

other: Dryness of the skin

Basis:

animal: all tested animals

Reversibility:

not reversible

Remarks on result:

other: Between days 5 and 15, a dryness of the skin was observed at the treatment site of the three animals

Irritant / corrosive response data:

- Moderate reversible cutaneous reactions were observed after removal of the dressing applied during 4 hours. They consisted of erythema (scores of 1 to 3) and oedema (score of 2). The mean score over 24, 48 and 72 hours for individual animals was 1.7, 1.7 and 2.3 for erythema and 1.3, 1.3 and 1.3 for oedema (see Table 7.3.1/1).
- No ulceration or necrosis was noted.

Other effects:

- A dryness of the skin was observed at the treatment site of one animal on day 4 and daily until day 15 for the three animals.
- Any change in the animal's behaviour was noted.

Any other information on results incl. tables

Table 73.1/1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema	Edema
	Max. score: 4	Max. score: 2
60 min	2/1/2	0/0/2
24 h	2/1/2	2/2/2
48 h	2/2/3	2/2/2
72 h	1/2/2	0/0/0
Average 24h, 48h, 72h	1.7/1.7/2.3	1.3/1.3/1.3
Reversibility*)	c	c
Average time (unit) for reversion	7 days	72 hours

 

*) 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 of this study, Anisole was slightly irritating to the rabbit skin. The mean score over 24, 48 and 72 hours for individual animals was 1.7, 1.7 and 2.3 for erythema and 1.3, 1.3 and 1.3 for oedema. These cutaneous reactions were fully reversible within 7 days. Based on these results, no classification is required according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC). According to UN GHS criteria the substance is classified skin. irrit. Cat. 3, H316.

Executive summary:

In a primary dermal irritation study performed according to the OECD guideline No. 404 and in compliance with the GLP, three male

New Zealand rabbits were dermally exposed to 0.5 mL of undiluted Anisole for 4 hours under a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24 and 72 hours after removal of the dressing and then daily until day 15. The mean values of the scores for erythema and oedema were calculated for each animal.

Moderate reversible cutaneous reactions were observed after removal of the dressing applied during 4 hours. They consisted of erythema (scores of 1 to 3) and oedema (scores of 2). The mean score over 24, 48 and 72 hours for individual animals was 1.7, 1.7 and 2.3 for erythema and 1.3, 1.3 and 1.3 for oedema. By day 7, no erythema nor oedema were observed.

Between days 5 and 15, a dryness of the skin was observed at the treatment site of the three animals. No ulceration or necrosis was noted.

Under the test conditions of this study, Anisole is considered as slightly irritating to skin. However, according to the classification criteria laid down in Regulation (EC) 1272/2008 (CLP) and in Council Directive 67/548/EEC (and subsequent adaptations), the test item should not be classified as irritating to the skin.

This skin irritation study is classified as acceptable. It satisfies the guideline requirement for a skin irritation in the rabbit.