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

Endpoint summary

Description of key information

Oral:

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

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

Dermal:

A study was performed to assess the acute dermal toxicity of test item to the rat following the method described in OECD 402.

The acute lethal dermal dose to rats of test item was demonstrated to be greater than 2000 mg/kg bodyweight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

Specific details on test material used for the study:

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

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.

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.

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.

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

500 mg/kg bw

Based on:

test mat.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Quality of whole database:

1 (reliable without restriction)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Acute toxicity:

Acute oral toxicity test, EC B.1: LD50: >500 mg/kg

Acute dermal toxicity test, OECD 402: LD50: > 2000 mg/kg

Therefore in accordance with Regulation (EC) No. 1272/2008 (amended by 286/2011) Table 3.1.1, this substance should be classified as Category 4 for acute oral, not be classified for acute dermal. No conclusion can be drawn for acute inhalation toxicity due to data lacking.

 

Specific target organ toxicity-single exposure:

Oral:

Acute oral toxicity test, EC B.1:

Mortality: no mortalities occurred at 500 mg/kg (0/10)

Clinical observations: confined to piloerection and hunched posture, seen in all rats. Recovery was complete in all instances by Day 6.

Necropsy: No abnormalities were noted

Dermal:

Acute dermal toxicity test, OECD 402:

Mortality: no deaths (0/10)

Clinical observations:no clinical signs of reaction to treatment observed

Necropsy: No abnormalities were noted

 

In accordance with Regulation (EC) No. 1272/2008 section 3.8.2.1.7., the effects observed are not considered as adverse effects that support classification, therefore this substance should be not classified.