4H-Pyrido[1,2-a]pyrimidin-4-one, 3-(2-chloroethyl)-9-hydroxy-2-methyl-, hydrochloride (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-06-02 to 2003-006-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study followed OECD guideline 423 (Acute Oral Toxicity-Acute Toxic Class Method), however, the test substance is not adequately characterized and insufficient information is provided on the test animals.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

modified on 2001-12-17

Deviations:

yes

Remarks:

: 1) no characterization of the test material; 2) not sufficient data for the animals tested.

Principles of method if other than guideline:

Study is performed according to SPL Standard Method 520.01

GLP compliance:

no

Remarks:

The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report had not been audited by the QA Unit. No formal claim of GLP compliance was made for the study.

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-CHLOROETHYL)-9-HYDROXY-2-METHYL-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE HYDROCHLORIDE (1:1)

EC Number:

617-648-0

Cas Number:

849727-62-4

Molecular formula:

C11H11ClN2O2.HCl

IUPAC Name:

3-(2-CHLOROETHYL)-9-HYDROXY-2-METHYL-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE HYDROCHLORIDE (1:1)

Test material form:

solid: particulate/powder

Test animals

Species:

mouse

Strain:

CD-1

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 28-38 g
- Fasting period before study: Yes, no further data provided
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE: no data


MAXIMUM DOSE VOLUME APPLIED:
- no data


DOSAGE PREPARATION (if unusual):
- no data


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: advised in OECD-423 guideline

Doses:

300 mg/kg bw (two groups); 2000 mg/kg bw stepwise procedure

No. of animals per sex per dose:

3 females/group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and clinical signs were observed 30 minutes, 1, 2, and 4 hours after dosing, and daily for 14 days after dosing. Body weights were recorded on days 0, 7, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight, and macroscopic examinations.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 500 mg/kg bw

Mortality:

All animals treated at a dose level of 2000 mg/kg bw were found dead one or two hours after dosing. There were no deaths noted in animals treated at a dose level of 300 mg/kg bw.

Clinical signs:

other: The animals treated with 2000 mg/kg bw, had hunched posture, lethargy, ataxia, decreased respiratory rate, and laboured respiration. No clinical signs were observed in animals treated at 300 mg/kg bw.

Body weight:

other body weight observations

Remarks:

The bodyweight was within the normal range of variability.

Gross pathology:

The animals treated with 300 mg/kg bw had no abnormalities observed during necropsy. At 2000 mg/kg dose level, haemorrhagic lungs, dark liver, dark kidneys, and haemorrhagic gastric mucosa were observed in all animals.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of the test substance in female CD-1 strain mouse was estimated to be in the range of 300-500 mg/kg bodyweight. However, based on expert judgement it is concluded that since only 300 and 2000 mg/kg were tested in this study, it cannot be estimated that the LD50 will be situated in the range 300 - 500 mg/kg according to the guidelines.