Benzonitrile, 4-[(1,6-dihydro-4-hydroxy-6-oxo-2-pyrimidinyl)amino]-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-06-18 to 2003-07-15

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

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)

Deviations:

yes

Remarks:

Only a study summary was available for review which provided limited details on the test substance, tested animals, methodology and results.

GLP compliance:

no

Remarks:

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

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-[(4,6-dihydroxypyrimidin-2-yl)amino]benzonitrile

EC Number:

609-425-1

Cas Number:

374067-80-8

Molecular formula:

C11H8N4O2

IUPAC Name:

4-[(4,6-dihydroxypyrimidin-2-yl)amino]benzonitrile

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): JNJ-4370561-AAA (T002326)
- Physical state: solid (powder)
- Appearance: slight beige powder

Test animals

Species:

mouse

Strain:

other: outbred albino

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 23-29 g
- Fasting period before study: animals were fasted before treatment but the fasting period was not provided

ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data


MAXIMUM DOSE VOLUME APPLIED:
- no data


DOSAGE PREPARATION:
- no data


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data

The test item was administered orally as a suspension in distilled water.

Doses:

300 or 2000 mg/kg bw
A group of three fasted females was treated with the test material at a dose level of 300 mg/kg bodyweight. Based on the results of this dose level further groups of fasted females were treated at a dose level of 2000 mg/kg bodyweight. Dosing was performed sequentially.

No. of animals per sex per dose:

3 (1 group for 300 mg/kg bw and 2 groups for 2000 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were examined for clinical signs and mortality at approximately 30 minutes, 1, 2, 3 and 4 hours after treatment and then daily during test days 1-14; body weights were recorded on day 0 (prior to administration) and on days 7 and 14. In addition, body weight gain was monitored during week 1 and week 2
- Necropsy of survivors performed: yes

Statistics:

no data

Results and discussion

Preliminary study:

not applicable

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

There were no abnormalities in macroscopic observations.

Other findings:

- Organ weights: no data
- Histopathology: no data
- Potential target organs: no data
- Other observations: no data

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the described conditions of the study, the acute oral median lethal dose (LD50) of the test substance in the female outbred albino mouse was estimated to be greater than 2000 mg/kg bw.