2,4(1H,3H)-Pyrimidinedione, 1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-.beta.-L-erythro-pentofuranosyl]-5-methyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10.02.2004 - 26.03.2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

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:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[(2S,3R,5S)-3-[(4-methylbenzoyl)oxy]-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl 4-methylbenzoate

EC Number:

608-497-1

Cas Number:

3056-13-1

Molecular formula:

C26 H26 N2 O7

IUPAC Name:

[(2S,3R,5S)-3-[(4-methylbenzoyl)oxy]-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl]methyl 4-methylbenzoate

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: approximately 8 weeks
- Fasting period before study: Animals were fasted overnight until 3 h after application of the test substance.
- Housing: Animals were housed individually in Makrolon type III cages with wire mesh lids and aspen wood chips as bedding material.
- Diet: Altromin 1324 forte (Altromin, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 22.2
- Humidity (%): average of 47.9
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

Doses:

300 mg/kg and 2000 mg/kg

No. of animals per sex per dose:

4 groups of 3 females each

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Animals were observed periodically during the first 6 h after application of the test substance and thereafter at least daily until the end of observation period. Body weights were recorded on Days 0 (before application of the test substance), 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the scheduled termination of the study.

Clinical signs:

other: In the high dose group, 5/6 animals showed signs of reduced well-being in the period between 4 and 6 h post-application (unspecific alterations like sedation, apathy, piloerection, hunched posture or closed eyes).

Gross pathology:

No treatment-related findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified