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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
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

Constituent 1
Chemical structure
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.

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