5-fluoro-2-methoxypyrimidin-4(3H)-one

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 June 2005 to 22 June 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

473-810-9

EC Name:

-

Cas Number:

1480-96-2

Molecular formula:

Hill formula: C5H5FN2O2 CAS formula: C5H5FN2O2

IUPAC Name:

5-fluoro-2-methoxy-3,4-dihydropyrimidin-4-one

Test material form:

solid: particulate/powder

Details on test material:

- Appearance: white powder
- Storage conditions of test material: at room temperature, protected from humidity and under nitrogen gas

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Sprague-Dawley Rj: SD (IOPS Han)
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Approximately 8 weeks old
- Weight at study initiation: Animals had a mean body weight ± standard deviation of 347 ± 7 g for the males and 217 ± 6 g for the females.
- Fasting period before study: No
- Housing: The animals were housed in polycarbonate cages with stainless steel lid (48 x 27 x 20 cm). Each cage contained one to seven animals of the same sex during the acclimation period and a single rat during the treatment period. Each cage contained autoclaved sawdust.
- Diet: ad libitum. All the animals had free access to adapted pelleted diet
- Water: Drinking water filtered by an FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: At least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 30 to 70 % (relative)
- Air changes: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod: 12 hour light/12 hour dark cycles

IN-LIFE DATES: Not reported

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal area of each animal. On the day before treatment, the dorsal area of each animal was clipped using an electric clipper. Only animals with healthy intact skin were used for the study.
- % coverage: Approximately 10 % of the total body surface of the animals (approximately 5 x 7 cm for males and 5 x 6 cm for females)
- Type of wrap if used: The test material and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage. This dressing prevented ingestion of the test material by the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None. On removal of the dressing, any residual test material was removed using a dry cotton pad.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- For solids, paste formed: No; the test material was placed on a hydrophilic gauze pad (pre-moistened with 2 mL of purified water)

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days.
- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test material, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15. From day 2 any local cutaneous reaction was recorded. The animals were weighed individually just before administration of the test material on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: Yes. On day 15, all surviving animals were killed by carbon dioxide asphyxiation. All study animals were subjected to a macroscopic examination as soon as possible after death. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No deaths occurred during the study.

Clinical signs:

Piloerection was observed in all animals within 1 hour of treatment. No more clinical signs were noted thereafter, until the end of the observation period (day 15).
No cutaneous reactions were observed during the study.

Body weight:

The body weight gain of the treated animals was similar to that of historical control animals.

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of the study, the LD50 has been determined to be greater than 2000 mg/kg in the rat.

Executive summary:

A study was conducted to investigate the acute dermal toxicity potential of the test material in accordance with the standardised guidelines OECD 402 and EU Method B.3 under GLP conditions.

The test material in its original form was applied to the clipped skin on the dorsal area of one group of ten Sprague-Dawley rats (five males and five females). The application was performed with a limit dose of 2000mg/kg. The test site was then covered by a semi-occlusive dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test material. At the end of the 14 day treatment period, all animals were subjected to necropsy.

No deaths were observed during the study. Piloerection was observed in all animals within 1 hour of treatment. No more clinical signs were noted thereafter, until the end of the observation period (day 15). No cutaneous reactions were observed during the study. The overall body weight gain of the animals was not considered to be affected by treatment with the test material. No apparent abnormalities were observed at necropsy in any animal.

Under the conditions of the study, the LD50 has been determined to be greater than 2000 mg/kg in the rat.