Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP- and Guidelinestudy with minor deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(4-aminophenyl)-1,2,4-oxadiazol-5(2H)-one
EC Number:
917-912-8
Cas Number:
864680-71-7
Molecular formula:
C8 H7 N3 O2
IUPAC Name:
3-(4-aminophenyl)-1,2,4-oxadiazol-5(2H)-one
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species, number of animals: 12 rats, 3 males (M) and 9 females (F)
Strain: CrlGlxBrlHan:WI (SPF quality)
Supplier: Charles River Deutschland GmbH, 97633 Sulzfeld,
Germany Age (Day 1): approximately 7 - 9 weeks
Body weight range (Day 1): males 210 - 220 g, females 126 - 152 g

Housing and target ranges of the climate conditions were as follows:
Room number: 35, building N81
Temperature: 22 ± 2°C
Relative humidity: 45 - 75%
Light/darkness cycle: 12/12 hours
Illumination period: 06:00 h - 18:00 h
Average illumination: approximately 60 lx (depending on the cage position; during work in the room the intensity is raised to
approximately 450 lx)
Air change: minimum of 10 air changes per hour

Food: pelleted dry food
Water: Tab water ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% aqueous hydroxyethylcellulose (Natrosol® 250 HX)
Doses:
100, 200, 2000 mg/kg
No. of animals per sex per dose:
3

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 200 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
100 mg/kg, 200 mg/kg: No mortality occurred in the three females treated per dose.
2000 mg/kg: One male was found dead on Day 7. No mortality occurred in the three females.
Clinical signs:
100 mg/kg, 200 mg/kg: On the day of administration and throughout the entire 14-day observation period, no clinical signs were observed in the three females treated per dose.

2000 mg/kg: In males, piloerection and urine of red color was observed on Day 1 (3.5 h and 3.75 h post administration). All males returned to normal on
Day 1 (6.25 h post administration). In rat No. 303, no clinical signs were seen from Day 2 to Day 6, but it was found dead in the morning of Day 7.
No further clinical signs were observed in animals No. 301 and No. 302 throughout the remaining observation period.
In females, piloerection observed on Day 1 (2.25 h post administration only) was the only clinical observation noted.
Body weight:
100 mg/kg, 200 mg/kg: No influence on body weight development was observed in the three females treated per dose.
2000 mg/kg: On Day 2, body weight of all three males treated was reduced. Also on Day 8, the two surviving males had a reduced body weight, but on Day 15, they had returned to normal. No influence on body weight development was seen in the three females treated.
Gross pathology:
100 mg/kg: No gross macroscopical changes were observed at necropsy of the three females treated.
200 mg/kg: Besides a dilation seen in the right ventricle of the heart in two rats, no gross macroscopical changes were observed
at necropsy of the three females treated.

2000 mg/kg: One male was found dead in the morning of Day 7 and at necropsy in an advanced state of necrolysis. Thus, no gross macroscopical
changes could be detected. No alterations were observed at necropsy of the two other males surviving the entire study period and, besides enlarged
adrenals in two rats, in the three females treated.

Any other information on results incl. tables

This study was designed to evaluate in rats the acute toxicity of BIBR 1048 OXA-AMIN, an intermediate in the synthesis ob BIBR 1048 MS, subsequent to a single oral administration by gavage. No mortality occurred at both 100 mg/kg and 200 mg/kg. At 2000 mg/kg, however, one male was found dead on Day 7. No mortality occurred in the three females. At 100 mg/kg as well as at 200 mg/kg, no clinical signs were observed on the day of administration and throughout the entire 14-day observation period. Subsequent to 2000 mg/kg, males showed piloerection and urine of red color on Day 1 (3.5 h and 3.75 h post administration). All males returned to normal on Day 1 (6.25 h post administration) and no further clinical signs were observed in two animals throughout the remaining observation period. Also in the third rat, no clinical signs were seen until Day 6, but it was found dead in the morning of Day 7. In females, piloerection observed on Day 1 (2.25 h post administration only) was the only clinical observation noted. Necropsy revealed no gross macroscopical changes at 100 mg/kg and, besides a dilation in the right ventricle of the heart in two females, at 200 mg/kg. At 2000 mg/kg, the male found dead in the morning of Day 7 was in an advanced state of necrolysis and thus, no gross macroscopical changes could be detected. No alterations at necropsy were observed in the two other males surviving the entire study period and, except enlarged adrenals in two rats, in the three females treated.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU