[1,1'-Biphenyl]-2-carboxylic acid, 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-yl)methyl]-, hydrochloride (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2 June - 22 June 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted in GLP compliance and in accordance with several internationally established guidelines (OECD, EEC guidelines, see below).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

485-140-4

EC Name:

-

Cas Number:

515815-48-2

Molecular formula:

C33 H30 N4 O2 x HCl

IUPAC Name:

4’-(2-Propyl-4-methyl-6-(1-methylbenzimidazolyl-2-yl)-benzimidazol-1-ylmethyl)biphenyl-2-carbonsäure Hydrochlorid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): BIBR 277 CL
- Physical state: solid
- Analytical purity: 99.3%
- Lot/batch No.: HE 815 HCl

Test animals

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: LPT Laboratory of Pharmacology, Löhnsdorf, Germany
- Age at study initiation: 6.5 months
- Weight at study initiation: 2.3 - 2.4 kg
- Housing: individually in 425mm x 600mm x 380 mm cages
- Diet (e.g. ad libitum): ssniff (R) K-H V2333 ad libitum, available before and after the exposure period.
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 55% +/- 15%
- Photoperiod (hrs dark / hrs light): 12 hrs each light/dark

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

500 mg per animal

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hrs after exposure

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm², dorsal area of the trunk of the animals.
- Type of wrap if used: gauze patch, non-irritating tape

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1, 24, 48, 72 hours

Score:

0

Max. score:

0

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48, 72 hours

Score:

0

Max. score:

0

Any other information on results incl. tables

Under the present tes conditions, none of the three rabbits exposed to BIBR 277 CL at 500mg for 4 hours (patch application, semi-occlusive) showed any substance-related lesions. There were no systemic intolerance reactions. For individual results, see attached table.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

BIBR 277 is non-irritating to skin according to EU classification.