3-(2-hydroxyethyl)-1H,3H-quinazoline-2,4-dione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-03-07 to 2006-05-08

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-hydroxyethyl)-1H,3H-quinazoline-2,4-dione

EC Number:

214-897-3

EC Name:

3-(2-hydroxyethyl)-1H,3H-quinazoline-2,4-dione

Cas Number:

1207-75-6

Molecular formula:

C10H10N2O3

IUPAC Name:

3-(2-hydroxyethyl)-1,2,3,4-tetrahydroquinazoline-2,4-dione

Test material form:

solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 00475665RT001200G1A291
- Expiration date of the lot/batch: 2006-06-30
- Purity: 100%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (range of 20 ± 5°C), light protected
- Solubility and stability of the test substance in the solvent/vehicle: stability of test item dilution: unknown in PEG 300

Test animals

Species:

rat

Strain:

Wistar

Remarks:

SPF

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd., Laboratory Animal Services CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: 12 weeks
- Weight at study initiation: ranged between 174.3 to 201.4 grams
- Fasting period before study: 18 to 19 hours (access to water was permitted); food was provided again approximately 3 hours after dosing
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz/Switzerland).
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 001/06 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland) ad libitum.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 22 +/- 3° C
- Humidity (%): 30-70 %
- Air changes (per hr): 10 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Justification for choice of vehicle: non-GLP solubility trial in which PEG 300 was found to be a suitable vehicle.
- Lot/batch no. (if required): 120471944705164
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The dose formulations were made shortly before each dosing using a spatula, a magnetic stirrer and an Ultra-Turrax as homogenizers. The test item was weighted into a tared glass beaker on a suitable precision balance and the vehicle added. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Doses:

Single dosage 2000 mg/kg bw

No. of animals per sex per dose:

3 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/viability: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Body weights: On days 1 (prior to test), 8 and 15
Clinical signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.
- Necropsy of survivors performed: yes, macroscopic examination of survivors. No organs or tissues were retained

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

Mild clinical signs were observed in all 6 treated animals on the day of dosing. A slight to moderate ruffled fur was noted in the animals between 30 minutes and 3 or 5 hours after dosing, or 1-3 hours after dosing. This was combined with a hunched posture in three of the animals 1-3 hours after dosing. All animals were found slightly sedated 1-3 hours after the treatment. No clinical signs were observed on the remaining days of the test.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of T001200 after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight.