N*4*-(3-Chloro-4-fluoro-phenyl)-7-[(S)-(tetrahydro-furan-3-yl)oxy]-quinazoline-4,6-diamine

Acute Toxicity: oral

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

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 (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

N4-(3-chloro-4-fluorophenyl)-7-[(3S)-oxolan-3-yloxy]quinazoline-4,6-diamine

EC Number:

921-874-8

Cas Number:

314771-76-1

Molecular formula:

C18 H16 Cl F N4 O2

IUPAC Name:

N4-(3-chloro-4-fluorophenyl)-7-[(3S)-oxolan-3-yloxy]quinazoline-4,6-diamine

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Wistar Han

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Male and Female, Wistar Han strain rats were obtained from Charles River Deutschland GmbH
Sandhofer Weg 7 D-97633 Sulzfeid
-The rats were in body weight range of: 214 -228 g (male) and 183 -204 g (female)
-Rats were approximately: 8 weeks old (male) and 9 weeks old (female)

CONDITIONS
-Drinking water in bottles was offered ad libitum.
-Diet: ssniff® R/M-H VI530 (ssniff Spezialdiaten GmbH, D-59494 Soest, served as food. Feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
- AnimalHousing: Granulated textured wood (Granulate A2, J. Brandenburg, D-49424 Goldenstedt) was used as bedding material for the cages.
The cages were changed and cleaned twice a week.
Periodic analysis of the bedding material for contaminants based on EPA/USA is conducted
at least once a year by LUFA-ITL.
During the 14-day observation period the animals were kept in groups of 2 - 3 animals in
MAKROLON cages (type III) at a room temperature of 22°C ± 3°C (maximum range) and a
relative humidity of 55 % ± 15% (maximum range).
-The rooms were lit (150 lux at approx. 1.5 m room height) and darkened for periods of 12
hours each.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% aqueous hydroxyethylcellulose suspension

Doses:

2000mg/kg b.w.

No. of animals per sex per dose:

3male and 3 female

Control animals:

not specified

Details on study design:

Following administration, observations were made and recorded systematically with
individual records being maintained for each animal.

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.
- During the follow-up period, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms
subsided, thereafter each working day.
Attention was also paid to possible tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Observations on mortality were made at least once daily in order to minimize loss of animals
during the study.
- Individual body weights were recorded before administration of the substance and thereafter in weekly intervals up to the end of the study, and at death.
- Changes in weight were calculated and recorded.
- At the end of the experiments all surviving animals were sacrificed, dissected and inspected macroscopically.

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:

other: Under the present test conditions, a single oral administration of 2000 mg CDBA05788S/kg b.w. to rats revealed no toxic symptoms.

Body weight:

other body weight observations

Remarks:

the animals gained the expected weight throughout the whole study

Gross pathology:

No histopathoiogy was carried out as no macroscopical findings were noted at autopsy.

Applicant's summary and conclusion

Interpretation of results:

other: "not classified according to CLP

Conclusions:

Under the present test conditions, a single oral administration of 2000 mg CDBA0578BS/kg b.w. to rats revealed no toxic symptoms.
The animals gained the expected weight throughout the whole study period.
No autopsy findings were noted.
LD50 (oral; 14 days): >2000 mg/kg b.w,