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EC number: 203-327-9 | CAS number: 105-75-9
Skin irritation / corrosion
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:
- other: GLP Study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- Dibutyl fumarate
- EC Number:
- 203-327-9
- EC Name:
- Dibutyl fumarate
- Cas Number:
- 105-75-9
- Molecular formula:
- C12H20O4
- IUPAC Name:
- dibutyl but-2-enedioate
- Details on test material:
- Name: "DIBUTYLFUMARAT".Chemical name: Fumaric acid dibutyl ester.Trade name: DBF.CAS No.: 105-75-9.Batch No.: EMBF 101.Purity: At least 99 %.Density: 0.99 g/cm3.Melting point: -19 °C.Solubility in water: Insoluble.Storage: In the refrigerator, in the dark.Date of expiry: June 1999.
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system 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. 101: 3.1 kg and 3.4 kg.Animal No. 102: 2.8 kg and 3.1 kg.Animal No. 103: 2.4 kg and 2.7 kg.Hygiene: Optimal hygienic conditions.Room number: EH1-17.Room temperature: Average of 20 °C.Relative humidity: Average of 55 %.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: 11 days.
Test system
- Type of coverage:
- semiocclusive
- Preparation of test site:
- other: 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, 72 h and 6 and 8 d after patch removal (ending individually).
- 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, 72 h and 6 and 8 d after patch removal (ending individually).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
- Remarks:
- mean
- Time point:
- other: 1, 24, 48, 72 h, 6d
- Score:
- 2
- Max. score:
- 2
- Reversibility:
- fully reversible within: 6 d
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Remarks:
- mean
- Time point:
- other: 1, 24, 48, 72 h, 6d, 8d
- Score:
- 1.3
- Max. score:
- 2
- Reversibility:
- fully reversible within: 8 d
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Remarks:
- mean
- Time point:
- other: 1, 24, 48, 72 h, 6d, 8d
- Score:
- 2
- Max. score:
- 2
- Reversibility:
- fully reversible within: 8 d
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Remarks:
- mean
- Time point:
- other: 1, 24, 48, 72 h, 6d
- Score:
- 3
- Max. score:
- 3
- Reversibility:
- fully reversible within: 6 d
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Remarks:
- mean
- Time point:
- other: 1, 24, 48, 72 h, 6d, 8d
- Score:
- 0
- Max. score:
- 0
- Reversibility:
- other: not applicable
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Remarks:
- mean
- Time point:
- other: 1, 24, 48, 72 h, 6d, 8d
- Score:
- 1
- Max. score:
- 1
- Reversibility:
- fully reversible within: 6 d
- 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 to well-defined erythema (scores "1" and "2") were noted in all animals. The lesions were observed from 1 h p.a. to a maximum of 6 d p.a.Oedema: Very slight oedema (score "1") and moderate oedema (score "3") was noted in 1/3 animals each. The lesions then gradually returned to normal and 6 d p.a. no swellings were detectable.
- Other effects:
- None
Any other information on results incl. tables
| Mean Scores for Animal No.: | ||
| 101 | 102 | 103 |
Erythema / Eschar: | 2.0 | 1.3 | 2.0 |
Oedema: | 3.0 | 0.0 | 1.0 |
Applicant's summary and conclusion
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The test substance caused 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 require classification for skin irritation (R 38 - Irritating to skin).
- 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 "DIBUTYLFUMARAT" 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, 72 h and 6 and 8 d after patch removal (ending individually).
Results
General signs of toxicity
No general toxic effects were observed.
Skin examination
Very slight to well-defined erythema was noted in all animals. The lesions lasted until a maximum of 6 days after the patch removal.
Moderate oedema was seen in one animal and very slight oedema in another animal, lasting until a maximum of 72 hours after the end of the exposure.
Conclusion
The following mean scores were calculated for each animal from the individual examinations performed 24 h, 48 h and 72 h p.a.:
Mean Scores for Animal No.:
101
102
103
Erythema / Eschar:
2.0
1.3
2.0
Oedema:
3.0
0.0
1.0
Lesions were reversible in all animals within 8 days p.a.
The test substance"DIBUTYLFUMARAT"
caused 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 require classification for skin irritation (R 38 - Irritating to skin). No classification is derived under CLP, as none of the criteria for classification in category 2 is met.
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