[1,1'-Biphenyl]-2-carbonitrile, 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-yl)methyl]-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 May - 6 June 2007

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, see below).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

480-420-2

EC Name:

-

Cas Number:

144702-27-2

Molecular formula:

C33 H29 N5

IUPAC Name:

4'-{[4-methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-yl]methyl}-[1,1'-biphenyl]-2-carbonitrile

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): BIBR 277 Nitril
- Physical state: Solid
- Analytical purity: 99.7%
- Purity test date: 20 March 2007
- Lot/batch No.: 80A
- Expiration date of the lot/batch: 08 March 2008
- Stability under test conditions: yes
- Storage condition of test material: At room temperature, dark and dry

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles Liver Laboratories, Budapest, Hungary
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 229 - 281g
- Housing: individually caging
- Diet (e.g. ad libitum): ssniff(R) ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 14d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C - 23°C
- Humidity (%): 38-66%
- Air changes (per hr): 8-12
- Photoperiod (hrs dark / hrs light): each 12 hrs

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: trunk
- % coverage: 10% of the total body surface
- Type of wrap if used: sterile gauze pads

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washing with water was performed
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg b.w.
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of exposure:

24h

Doses:

single dose

No. of animals per sex per dose:

5 per sex/dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1 and 5hrs after exposure, then once in the following 13 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none of the test animals died

Clinical signs:

other: none observed

Gross pathology:

no macroscopic observations were made

Applicant's summary and conclusion

Conclusions:

Under the test conditions, the 24h dermal LD50 of BIBR 277 Nitril in rats was determined to be > 2000 mg/kg b.w..
BIBR 277 Nitril does not meet the classification criteria according to regulation 2001/59/EC for classification and labelling of dangerous substances.