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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 30 - May 27 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(3-Chloro-4-fluoro-phenyl)-{6-nitro-7-[(S)-(tetrahydro-furan-3-yl)oxy]-quinazolin-4-yl}-amine
EC Number:
925-395-5
Cas Number:
314771-88-5
Molecular formula:
C18 H14 Cl F N4 O4
IUPAC Name:
(3-Chloro-4-fluoro-phenyl)-{6-nitro-7-[(S)-(tetrahydro-furan-3-yl)oxy]-quinazolin-4-yl}-amine

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
male and female Wistar Hann strain obtained from Charles River Deutschland GmbH
body weight : 169 -184 g on day 1
age: approx. 9 weeks on day 1

CONDITIONS:
Diet: ssniff R/M-H V1530 served as food

Housing:
- during the 14-day observation period, the animals were kept in groups of 3 animals in MAKROLON cages (type III) at a room temperature of 22degC +/- 3degC (maximum range) and a relative humidity of 55% +/- 15% (maximum range).
- rooms were lit (150 lux at approx. 1.5 m room height) and darkened for periods of 12 hours each

DRINKING WATER:
- drinking water in bottles was offered ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% aqueous hydroxyethylcellulose
Details on oral exposure:
the test substance is administered orally by gavage at a single dose level to a group of experimental animals.
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
3 male and 3 female
Control animals:
no
Details on study design:
- Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All surviving animals were observed for a period of 14 days.

- Observations on mortality were made at least once daily

- individual body weights were recorded before administration of the test substance and thereafter in weekly intervals up to the end of the study, and at death. Changes in weight were calculated and recorded.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
none
Body weight:
All rats achieved body weight gains during the first and second weeks of study
Gross pathology:
none

Applicant's summary and conclusion

Interpretation of results:
other: not classified according to CLP
Conclusions:
Under the present test eonditions, a single oral administration of 2000 mg BIBW2992MA2/CDBA0573BS/kg b.w. to rats revealed no toxic symptoms.
The animals gained the expected body weight throughout the whole study period.
No autopsy findings were noted.
LD50 (14 days): > 2000 mg/kg b.w.