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: Guideline- and GLP-Study without deviations

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
BIBR 1048 OXA-ESTER
IUPAC Name:
BIBR 1048 OXA-ESTER
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rabbit
Strain:
Himalayan
Details on test animals or test system and environmental conditions:
Species/strain: rabbit / Himalayan
Breeder: LPT Laboratory of Pharmacology and Toxicology KG, branch Lohndorf, D-24601 Lohndorf/Post Wankendorf
Selection of species: the rabbit is a commonly used non-rodent species for acute dermal irritation/corrosion tests (patch test)
Sex: male animals
Number of animals: 3
Age: approx. 4 months
Initial body weight: animal no. 1: 2.7 kg
animal no. 2: 2.5 kg
animal no. 3: 2.2 kg


Identification of animals Duration of study: by tattooed number assigned by the Lohndorf breeding station
Duration of study: at least 20 adaptation days, 1 test day and a follow-up period of 72 hours

Diet:
ssniff® K-H V2333 (ssniff Spezialdiaten GmbH, D-59494 Soest) served as food. The food was available ad libitum before and after the exposure period.
At regular intervals (at least twice a year), the food is analysed for contaminants by LUFA-ITL.

Drinking water:
Drinking water was offered ad libitum before and after the exposure period. Samples of the drinking water are analysed according to the 'Deutsche
Trinkwasserverordnung 2001' [German Regulations on drinking water 2001] by the Wasserbeschaffungsverband Harburg, D-21220 Seevetal twice a year.
In addition, drinking water samples taken at LPT are analysed by LUFA-ITL once a year for means of bacteriological investigations according to the
'DeutscheTrinkwasserverordnung 2001, Anlage 1' [German Regulations on drinking water 2001, Addendum 1].

Housing:
Before and after the 4-hour exposure period, the animals were kept singly in cages measuring 400 mm x 500 mm x 370 mm (manufacturer:
Dipl. Ing. W. EHRET GmbH, D-16352 Schonwalde) at a room temperature of 20°C + 3°C (maximum range) and relative humidity of 30% - 70% (maximum range).
Deviations from the maximum range caused for example during cleaning procedures are dealt with in SOPs.
During the exposure period, the animals were kept singly in restrainers which allowed free movement of the head but prevented a complete body turn.
The cages excluded irritation of the skin by excrements and urine.
The rooms were lit (150 lux at approx. 1.5 m room height) and darkened on a 12-hour light/12-hour dark cycle (light 6.00 a.m. to 6.00 p.m., dark 6.00 p.m. to 6.00 a.m.).
Certificates of analysis of diet, drinking water and bedding material are QAU archived.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
other: untreated flank of each amimal
Amount / concentration applied:
A dose of 500 mg was applied to the test site (area: approx. 6 cm2). The test item was moistured with the smallest amount of water sufficient to
ensure good skin contact (1000 mg of the test item was mixed with 1.0 mL aqua ad iniectabilia3, 1000 mg of this paste was applied per patch and
animal (500 mg test item/animal)).
Duration of treatment / exposure:
4 h
Observation period:
The duration of the observation period was sufficient to evaluate fully the reversibility of the effects observed. However, the experiment would be
terminated at any time the animals showed continuing signs of severe pain or distress. To determine the reversiblily of effects, the animals would
be observed up to 14 days after removal of the patches. If reversibility was seen before 14 days, the experiment was terminated at that time.
Number of animals:
3
Details on study design:
Approximately 24 hours before the test, the fur was removed by closely clipping the dorsal area of the trunk of the animals. Care was taken to avoid
abrading the skin. Only animals with healthy intact skin were used.

The test item was applied to the patch, it was attached to the skin in such a manner that there was good contact and uniform distribution of the test
item on the skin. The patch was held in contact with the skin by means of a suitable semi-occlusive dressing with non-irritating tape for the duration of the exposure period. Access by the animals to the patch and ingestion or inhalation of the test item was prevented.
During the exposure the animals were kept in comfortable restrainers. At the end of the exposure time no residual test item had to be removed.

Initial test:
It was expected that the test item did not produce severe irritancy or corrosion, the test was started using one animal, receiving a single patch
for an exposure period of four hours.

Confirmatory test:
As neither a corrosive effect nor a severe irritant effect was observed in the initial test after a four hour exposure, the test was completed using
two additional animals, each with one patch only, for an exposure period of four hours.

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1-72 h
Score:
0
Max. score:
0
Reversibility:
no data
Irritant / corrosive response data:
Under the present test conditions, none of three rabbits exposed for 4 hours to 500 mg testsubstance/patch and animal
(semi-occlusive condition) showed any test item-related lesions.
There were no systemic intolerance reactions.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the present test conditions, none of three rabbits exposed for 4 hours to 500 mg test substance/patch and animal
(semi-occlusive condition) showed any test item-related lesions. There were no systemic intolerance reactions.

According to the EC-Commission directive 67/548/EEC and its subsequent amendments on the approximation of the laws, regulations and administrative
provision relating to the classification, packaging and labelling of dangerous substances and the results obtained under the present test conditions,

The test substance was non-irritating to skin, hence, no labelling is required.