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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1998-11-25 to 1998-12-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

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.: 960509
Purity: not specified

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: eight to eleven weeks
- Weight at study initiation: 224 to 258 g
- Housing: They were housed individually in metal cages (RS Biotech Sub-Dividable Rodent Cages - polished stainless steel (20cm high x 39cm wide x 39cm long)). The cages were fitted with grid floors to ensure rapid removal of waste material to undertrays. The cages were suspended in mobile stainless steel racks. The animals were returned to group housing on Day 8 of the study.
- Diet: standard laboratory rodent diet, ad libitum
- Water: ad libitum
- Acclimation period: six day at minimum

ENVIRONMENTAL CONDITIONS
- Temperature: 20-21 °C
- Humidity (%): 30-57
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

methylcellulose

Details on dermal exposure:

TEST SITE
One day prior to treatment, hair was removed from the dorso-lumbar region of each rat with electric clippers taking care to avoid damaging the skin, exposing an area equivalent to approximately 10% of the total body surface area.
The test substance was applied by spreading it evenly over the prepared skin. The treatment area (approximately 50 mm x 50 mm) was covered with porous gauze held in place with a non-irritating dressing and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
At the end of the 24 hours exposure period the dressings was carefully removed and the treated area of skin was washed with warm water (38°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3 mL/kg bodyweight
- Concentration (if solution): 66.67% w/v in 1% aqueous methylcellulose

VEHICLE
- Concentration (if solution): 1% aqueous methylcellulose

Duration of exposure:

24 h

Doses:

2000 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: at least twice daily
Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days animals were observed on at least two occasions during the day (once in the morning and again at the end of the experimental day, with the exception of the day of study termination - morning only).
Dermal responses: Local dermal irritation at the treatment site was assessed daily
Bodyweight: recorded on Days 1 (prior to dosing), 8 and 15.

- Necropsy of survivors performed: yes, All animals were killed by cervical dislocation at study termination (Day 15) and subjected to macroscopic examination

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no deaths

Clinical signs:

other: no evidence of systemic response in any animal

Gross pathology:

No macroscopic abnormalities were observed

Other findings:

- Dermal responses: Slight to well defined erythema with or without slight oedema was observed in three males and five females, resolving completely in all males by Day 4 and in all females by Day 8. In addition, localised spots and/or scabbing was observed in one male and one female rat. No dermal irritation was seen in the remaining two animals.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

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

Executive summary:

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

A group oftenrats (five males and five females) received a single topical application of the test substance formulated at a maximum practical concentration in 1% aqueous methylcellulose at a dosage of 2000 mg/kgbodyweight (EEC and OECD limit dosage). All animals were killed as scheduled at study termination (Day 15) and subjected to a macroscopic examination.

There were no clinical signs of reaction to treatment observed in any animal throughout the study.

Slight to well defined erythema with or without slight oedema was observed in eight rats, resolving completely by Day 8. In addition, localised spots and/or scabbing was observed in two of these animals. No dermal irritation was seen in the remaining two animals.

No bodyweight gain was observed in one animal on Day 8. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study.

No macroscopic abnormalities were observed in any of the animals killed at study termination.

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