4-tert-butylbenzonitrile

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

january - march 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

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

Test material

Test material information

Constituent 1

Reference substance name:

4-tert-butylbenzonitrile

EC Number:

224-137-2

EC Name:

4-tert-butylbenzonitrile

Cas Number:

4210-32-6

Molecular formula:

C11H13N

IUPAC Name:

4-tert-butylbenzonitrile

Test material form:

other: solution

Details on test material:

- Name of test material (as cited in study report): 4-tert-Butylbenzonitril
- Physical state: brown solution
- Analytical purity: > 94.2 %
- Impurities: 3-tert-Butylbenzonitril
- Lot/batch No.: FHI/TVT 281098
- Storage condition of test material: refrigerator (2-8 °C), in the dark
- Other: stable under conditions of storage

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: J. Schitkovits, A-2620 Natschbach
- Weight at study initiation: animal No. 61: 3.3 kg; animal No. 62: 3.2 kg; animal No. 63: 2.7 kg.
- Housing: Individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 76 cm x 59 cm x 35 cm.
- Diet (e.g. ad libitum): Altromin 2023 diet for rabbits, ad libitum. Random samples of the feed are analysed for contaminats by Altromin, D-32791 Lage.
- Water (e.g. ad libitum): tap water from an automatical watering system, ad libitum.
- Acclimation period: 11 days
- Identification: Labelling with felt-tipped pen in a pinna.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 20 °C
- Humidity (%): average of 55 %
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): artificial light from 6 a.m. to 6 p.m.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 mL of the test substance

Duration of treatment / exposure:

4 hours

Observation period:

The treated areas and the surrounding untreated skin (control area) of the animals were examinated for erythema/eschar and oedema as well as for other local signs approximately 1, 24, 48 and 72 hours after patch removal. No examination were performed thereafter.

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: dorsal area of the trunk
- coverage: about 2.5 cm x 2.5 cm
- Type of wrap if used: Samples of 0.5 mL of the test substance, were spread on cellulose patches (PurZellin-Tupfer, obtained by Fa. Hartmann, A-2355 Wiener Neudorf) were applied to the test sites. They were held in place by fixing them marginally with non irritating tapes ("Blenderm" surgical tape, hypoallergic, 3M, Medical Products Division, St. Paul, MN 551444, USA). The application sites were covered semi-occlusively by a dressing (Self adhesive non woven fabric, hypoallergenic, made by Beiersdorf AG, D-20245 Hamburg).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed with wet Kleenex-tissues, if necessary.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erythema/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) or eschar formation (injuries in depht).

Oedema formation:
0 No oedema
1 Very slight oedema (barely perceptible).
2* Slight oedema (edges of area are well defined by definite raising).
3* Moderate oedema (raised approximately 1mm).
4* Severe oedema (raised more than 1 mm and extending beyond area of exposure).

* may indicate irritation (R38), according to EC-Guideline 93/21.
irreversible lesions require R34, according to EC-Guideline 93/21.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 h after end of exposure

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1 h after end of exposure

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritant / corrosive response data:

The treated skin of all three animals was scored for erythema and oedema. The test substance caused no adverse effects to the skin, except very
slight erythema in one animal 60 minutes after removal of the bandage. This effect was fully reversible within 24 h.

Other effects:

No general toxic effects were noted.

Any other information on results incl. tables

Table 1: Scores for the application sites. Individual data and means.

Time after the end of exposure	Erythema / Eschar			Oedema
	animal Nos			animal Nos.
	61	62	63	61	62	63
1 h	1	1	1	0	0	0
24 h	0	0	0	0	0	0
48 h	0	0	0	0	0	0
72 h	0	0	0	0	0	0
Mean (24-72 h)	0.0	0.0	0.0	0.0	0.0	0.0

Scoring system see section "details on study design".

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The treated skin of all three animals was scored for erythema and oedema. The test substance caused no adverse effects to the skin, except very
slight erythema in one animal 60 minutes after removal of the bandage. This effect was fully reversible within 24 h. This indicates that the test substance 4-tert-Butylbenzonitrile did not cause any skin irritation or corrosion in this study.

Executive summary:

The dermal irritation/corrosion potential of 4-tert-Butylbenzonitrile was examined in three female New Zealand White rabbits. Parts of there intact and shaved skin were exposed for 4 hours. The treated areas and the surrounding untreated skin (control area) of the animals were examined for erythema/eschar and oedema as well as for other local signs approximately 1, 24, 48, 72 hours after patch removal. Dermal irritation was described and recorded using a scoring system for erythema and oedema. The test substance caused no adverse effects to the skin, except very slight erythema in one animal 60 minutes after removal of the bandage. This effect was fully reversible within 24 h. This indicates that the test substance 4-tert-Butylbenzonitril did not cause any skin irritation or corrosion in this study.