6-ethyl-5-fluoro-4(3H)-pyrimidone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1996-05-29 to 1996-06-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

6-ethyl-5-fluoro-4(3H)-pyrimidone

EC Number:

422-460-5

EC Name:

6-ethyl-5-fluoro-4(3H)-pyrimidone

Cas Number:

137234-87-8

Molecular formula:

C6 H7 F N2 O

IUPAC Name:

6-ethyl-5-fluoro-3,4-dihydropyrimidin-4-one

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Batch No: Chichibu Lot No. 950704
Purity: 95.7%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan U.K. Ltd, Bicester, Oxon, England.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: four to seven weeks
- Weight at study initiation: 92 to 106 g
- Fasting period before study: overnight prior to and approximately 4 hours after dosing.
- Housing: housed in groups of up to five rats of the same sex in metal cages with wire mesh floors
- Diet: standard laboratory rodent diet, ad libitum
- Water: ad libitum
- Acclimation period: five day

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity (%): 30-70
- Air changes (per hr): 10 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5% w/v
- Amount of vehicle (if gavage): 10 mL/kg bodyweight

Doses:

500 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: Cages of rats were checked at least twice daily for any mortalities
Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of four hours). On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only).
Bodyweight: recorded on Days 1 (prior to dosing), 2, 3, 4, 8 and 15.
- Necropsy of survivors performed: yes, all animals were killed on Day 15 by cervical dislocation and subjected to macroscopic examination.

Results and discussion

Preliminary study:

A preliminary study was carried out by dosing one female rat at 500 and 2000 mg/kg bodyweight respectively.
The results of the preliminary study indicated that the acute lethal oral dose to female rats of test item was between 500 and 2000 mg/kg bodyweight.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

500 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 500 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: Piloerection was observed in all rats within three minutes of dosing. This sign persisted and was accompanied in all rats on days 1, 2 and 3 by hunched posture. There were no other clinical signs and recovery was complete in all instances by Day 6.

Gross pathology:

Macroscopic examination revealed no abnormalities.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The discriminating oral dose to rats of test item was established to be 500 mg/kg bodyweight.

Executive summary:

A study was performed to assess the acute oral toxicity of test item to the rat following the method described in EC B.1.

A group of ten fasted rats (five males and five females) was given a single dose by oral gavage of the test substance, formulated in distilled water and administered at a dose level of 500 mg/kg bodyweight.

There were no deaths in the main study. Clinical signs of reaction to treatment were confined to piloerection and hunched posture, seen in all rats. Recovery was complete in all instances by Day 6.

All rats achieved satisfactory bodyweight gains throughout the study.

Macroscopic examination of animals killed on Day 15 revealed no abnormalities.

The discriminating oral dose to rats of test item was established to be 500 mg/kg bodyweight.