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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2 June - 1 August 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, 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class 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: powder

Details on test material:

- Name of test material (as cited in study report): BIBR 277 Nitril
- Physical state: solid
- Analytical purity: 95.8%
- Purity test date: 22 April 2003
- Lot/batch No.: HE 818 Nitril

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland G,mbH, Sulzfeld, Germany
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 181 - 205g
- Housing: Makrolon type III cages, 3 animals per cage
- Fasting period before study: 16 hrs prior to start of experiments - 3 hrs after oral administration
- Diet (e.g. ad libitum): ssniff(R) R/M-H V1520 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 55% +/- 15%
- Photoperiod (hrs dark / hrs light): 12 hrs each

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% hydroxyethylcellulose suspension

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/lg b.w.

Doses:

one dose per animal at 2000 mg/kg b.w.

No. of animals per sex per dose:

each 3 female and male

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing: before and imediately after, and 5, 15, 20, 60 min and 3, 6, 24 hours after. All survivors were observed for a period of 14 days in total.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Changes of skin and fur, eyes and mucous membranes, repiratory and the circulatory, autonimic and central nervous system, somatomotor activity, behaviour pattern, possible tremor, convulsions, salvitation, diarrhoea, lethargy, sleep, coma.

Statistics:

none performed

Results and discussion

Preliminary study:

not performed due to the small number of animals used.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality occured in any of the animals.

Clinical signs:

other: no clinical signs were noted.

Gross pathology:

no autopsy findings were noted.

Other findings:

none

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Conclusions:

The 14 day LD 50 of BIBR 277 Nitril administered orally to rats was determined to be > 2000 mg/kg body weight.