.beta.-Alanine, N-[[2-[[(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)phenylamino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl-, ethyl ester, acetate (1:2)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 September 2003 to 20 April 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

bis(acetic acid); ethyl 3-{1-[1-methyl-2-({[4-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl]amino}methyl)-1H-1,3-benzodiazol-5-yl]-N-(pyridin-2-yl)formamido}propanoate

EC Number:

925-312-2

Cas Number:

1184044-93-6

Molecular formula:

C28 H27 N7 O5 x 2 C2 H4 O2

IUPAC Name:

bis(acetic acid); ethyl 3-{1-[1-methyl-2-({[4-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl]amino}methyl)-1H-1,3-benzodiazol-5-yl]-N-(pyridin-2-yl)formamido}propanoate

Test material form:

solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- females (F) Chbb:NZW (New Zealand White) strain rabbits were obtained from Biological Laboratory Service of Boehringer Ingelheim Pharma GmbH & Co. KG.
- The rabbits were in a body weight range of females 3.1 – 3.4 kg (day of application).
- Rabbits were approximately 5 - 6 months.

CONDITIONS
- Municipal drinking water were supplied ad libitum.
- The animals were offered Dry food (Kliba No. 3413.0.25, Provimi Kliba SA, CH-4303 Kaiseraugst, Switzerland)were supplied ad libitum.
- The food is analyzed regularly for major nutritive components and significant contaminants by the manufacturer. Water samples taken and the municipal water supplier conducts water analysis regularly.
- Diet and water are not considered to contain any contaminants which
might have influenced the experimental outcome of this study.
- Rabbits were housed individually in solid wire cages. The bottom of the cages were changed
at least once a week and cleaned. The target temperature and humidity ranges were 22 ± 2°C and 45-80% respectively.
- Light/darkness give a cycle of 12/12 h, with light cycle from 6.00 h to 18.00 h with average illumination approximately 60 lx (depending on cage position), which can
be increased to 450 lx during working time.
- Air circulation of approximately 10 air changes per hour.

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Amount / concentration applied:

Approximately 0.5 g of this test item mixture was administered per skin site.

Duration of treatment / exposure:

According to the test strategy described in OECD Guideline 404,
-(Group 1, initial test) only one animal was treated. Sequentially, the test item was administered to three skin sites for 3 min (area 1), 1 h (area 2), and 4 h (area 3), respectively.
Administration to the next skin area was only performed in the absence of serious skin alterations in the previous one.
-(Group 2, confirmatory test) the test item was administered to two more animals. Administered on the following day for 4 h at a single site only when no serious skin alterations occurred subsequent to 4 h of exposure on the first rabbit.

Observation period:

Following application of the test item,
1. the general appearance of the rabbits was inspected twice daily.
2. In the pretest period as well as on non-working days, the inspections were only performed once a day.
3. Body weight of the rabbits was recorded at allocation, on the day of application and at the end of the study.

Number of animals:

3

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48h

Score:

0

Max. score:

4

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72h

Score:

0

Max. score:

4

Applicant's summary and conclusion

Interpretation of results:

other: not classified acc. CLP

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Under the conditions of the present study, BIBR 1048 OXA-AMIDIN DIACETATE was well tolerated subsequent to topical application on rabbit skin.
There were no macroscopic signs of irritation or corrosion. In addition, there were no signs of systemic side effects or of skin alterations beyond the area of exposure. Thus, according to the Globally Harmonized Hazard Classification and Labeling Scheme (GHS), the test item
BIBR 1048 OXA-AMIDIN DIACETATE is not classified.