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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 April 1999 to 14 July 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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): dioctylfumarate
- Physical state: liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Species and strain: Rabbits, New Zealand White.
Supplier: J. Schitkovits, A-2620 Natschbach.
Number and sex: 3 females.
Body weight (at the start and at the termination of the study):
Animal No. 1: 2.8 kg and 2.9 kg.
Animal No. 2: 2.7 kg and 2.8 kg.
Animal No. 3: 2.4 kg and 2.6 kg.

Hygiene: Optimal hygienic conditions.
Room number: EH1-17.
Room temperature: Average of 20 °C.
Relative humidity: Average of 58 %.
Air exchange: 12 per hour.
Light: Artificial light from 6 a.m. to 6 p.m.
Cages: Individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 cm x 59 cm x 35 cm.
Feed: Altromin 2023 diet for rabbits, ad libitum. Random samples of the feed are analysed for contaminants by Altromin, D-32791 Lage.
Water: Tap water from an automatic watering system, ad libitum.
Identification: Labelling with felt-tipped pen in a pinna.
Acclimatisation: 8 days.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL per animal
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after patch removal.
Number of animals:
3
Details on study design:
Hair was clipped on the dorsal area of the trunk one day before the application. An electric hair clipper, Aesculap GH 204, with a 1 mm cutterhead was used.
The test sites were located on the dorsal thoracal region.
Samples of 0.5 ml of the test substance were spread on cellulose patches 1) in a size of about 2.5 cm x 2.5 cm and were applied to the test sites. They were held in place by fixing them marginally with non irritating tapes 2). The application sites were covered semi-occlusively by a dressing 3).
Access by the animal to the application sites was prevented by a plastic collar.
The duration of exposure was 4 hours.
At the end of the exposure period the dressing, the tapes with the patches and the collar were removed, residual test substance was removed with wet Kleenex-tissues, if necessary.
1) Pur Zellin-Tupfer, obtained by Fa. Hartmann , A-2355 Wiener Neudorf.
2) "Blenderm ®" surgical tape, hypoallergenic, 3M, Medical Products Division, St. Paul, MN 551444, USA.
3) Self adhesive non woven fabric, hypoallergenic, made by Beiersdorf AG, D-20245 Hamburg.
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 alterations approximately 1, 24, 48 and 72 hours after patch removal.
No examinations were performed thereafter.
The scores noted, 24, 48 and 72 h after the patch removal were decisive for the interpretation of the results and the conclusion.
The skin was examined using a cold light source KL 1500 electronic.
Dermal irritation was described and recorded according to the scoring scheme for acute dermal irritation/corrosion tests.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Irritant / corrosive response data:
All areas treated with the test substance and all control areas were normal before the application.
The control areas were normal at any observation time.
Erythema/eschar: Very slight erythema (score "1") was noted in all animals. The lesions were observed from 1 h p.a. to a maximum of 48 h p.a.
Oedema: Scores of "0", i.e. normal, were noted in all animals at each examination term.
Other effects:
None

Any other information on results incl. tables

 Table 1: Individual Irritation Scores

 

Mean Scores for Animal No.:

 

1

2

3

Erythema / Eschar:

0.7

0.3

0.7

Oedema:

0.0

0.0

0.0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance caused slight transient skin irritation. Based on the mean scores calculated from the individual examinations performed 24, 48 and 72 h p.a. and referring to Commission Directive 2001/59/EC the test substance does not require classification for skin irritation.
Executive summary:

Aim of the study

The aim of this study was to investigate possible irritation or corrosion by the test material following a single application to the intact skin of rabbits.

Methods

Methods and investigations were performed in conformance with the OECD Guideline 404 and the Directive 92/69/EEC, method B.4.

Administration of the test substance

0.5 ml "DIOCTYLFUMARAT" was applied via a patch to a site of about 2.5 cm x 2.5 cm of the intact skin of each of 3 rabbits and covered by semi-occlusive dressing.

The duration of the exposure was 4 hours.

Investigations

·     Body weights: at the start and at the termination of the test.

·     General signs of toxicity: once daily.

·     Skin examination: 1, 24, 48 and 72 h after patch removal.

Results

General signs of toxicity

No general toxic effects were observed.

Skin examination

Slight erythema was noted in all animals. The lesions lasted until a maximum of 48 h after the patch removal.

In conclusion, the test item is not a skin irritant according to CLP criteria.