Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 May - 10 July 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 guidelines, see below).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. QA statement)
Limit test:
yes

Test material

Constituent 1
Chemical structure
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
Details on test material:
- Name of test material (as cited in study report): BIBR 277 CL
- Molecular formula (if other than submission substance): C33H30N4O2*HCl
- Molecular weight (if other than submission substance): 514.6 + 36.5 g/mol
- Structural formula attached as image file (if other than submission substance): see reference substance
- Physical state: solid; sligh grey
- Analytical purity: 99.8 %
- Purity test date: 17. october 2005
- Lot/batch No.: 9
- Expiration date of the lot/batch: april 2006
- 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 river (europe) laboratories, inc toxi coop LTD.
- Age at study initiation: 8 to 10 weeks old
- Weight at study initiation: male: 279 - 290 g; female: 213 - 225 g
- Housing: Individual caging (1 animal/cage)
- Diet (e.g. ad libitum): sniff SM R/M-Z+H; ad libitum
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 23 °C
- Humidity (%): 41 to 69 %
- Air changes (per hr): 8 to 12 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours each

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: no details given
- % coverage: 10 % of the total body surface
- Type of wrap if used: plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water, after 24 hours of exposure

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): unchanged test item moistened with 0.5 ml

VEHICLE
- no vehicle
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations daily for 14 days; body weights on days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, pathology

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Among groups of males and groups of females 0 deaths were observed.
Clinical signs:
No behavioural changes were noted during the study. BIBR 277 CL caused no dermal alterations.
Body weight:
The mean body weight and the body weight gain of the animals were normal during the two-week observation period and similar to what is expected of untreated animals of the same age and strain. One female showed weight loss during the first week, however it was not considered toxicologically significant.
Gross pathology:
No macroscopic alterations due to the effects of the test item were found. Gross necropsy revealed pinprick-sized haemorrhages in the lungs (3/5 male, 1/5 female) and hydrometra in two female animals (2/5).
The haemorrhages in the lungs might be due to the method of anaesthesia and exsanguinations and are also observable in untreated animals after anaesthesia. Hydrometra due to the sex cycle of animals is a common alteration in experimental rats.

Any other information on results incl. tables

  Group     Observations       Frequency
 Male  Female
 2000 mg/kg bw  normal  5/5  5/5

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A limit test identified an LD50 of > 2000 ml/kg bw in male and female rats. The result is considered be reliable.