Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name "Isomaltulose Solution".
Trade name Isomaltulose Solution
Batch No. 03160483
Density 1.2 g/cm3 (20 °C)
Solubility in water unlimited.
Storage room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Species and strain: Rabbits, New Zealand White.
Supplier: Charles River Deutschland GmbH, D-88353 Kisslegg.
Number and sex: 3 females.
Body weight (at the start and at the termination of the study):
Animal No. 11: 2.3 kg and 2.4 kg.
Animal No. 12: 2.4 kg and 2.6 kg.
Animal No. 13: 2.5 kg and 2.6 kg.

Hygiene: Optimal hygienic conditions.
Room number: EI1-8.
Room temperature: Ranges from 19.32 to 20.83 °C.
Relative humidity: Ranges from 44.05 to 57.72 %.
Air exchange: 12 per hour.
Light: Artificial light from 6 a.m. to 6 p.m.
Cages: Individual caging in terulan cages, Ehret GmbH, A-3430 Tulln, 65 cm x 65 cm bottom area, 50 cm height.
Feed: Ssniff K-H maintenance diet for rabbits (item V-2333-000), ad libitum, supplied by Ssniff Spezialdiäten GmbH, 59494 Soest, Germany.
Water: Tap water from an automatic watering system, ad libitum.
Identification: Labelling with felt-tipped pen on a pinna and cage labels.
Acclimatisation: 7 days (animal No. 11) and 14 days (animal Nos. 12 and13)

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 of test substance was spread on gauze patches and applied to test sites.
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after patch removal
Number of animals:
3 females
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 skins of the animals were examined for local alterations one day before the administration of the test substance (after clipping of the hair) and immediately before the administration. 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:
overall irritation score
Basis:
mean
Time point:
other: 0-72
Score:
0
Remarks on result:
other: No effects observed
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
All animals were normal. No effects observed at any observation period.
Other effects:
None

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is not irritating.
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 "Isomaltulose Solution" 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 New Zealand White 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 (p.a.).

Results

General signs of toxicity

No general toxic effects were observed.

Skin examination

Erythema/eschar: Not observed at any observation point.

Oedema: Not observed at any observation point.

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.:

 

11

12

13

Erythema / Eschar:

0.0

0.0

0.0

Oedema:

0.0

0.0

0.0

   

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.