3-(2-chloroethyl)(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:

2006-03-28 to 2006-04-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented, GLP-compliant study performed according to OECD Guideline 423 and EU Method B.1 tris. No deviations were recorded.

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:

yes

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

225-795-3

EC Name:

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

Cas Number:

5081-87-8

Molecular formula:

C10H9ClN2O2

IUPAC Name:

3-(2-CHLOROETHYL)QUINAZOLINE-2,4(1H,3H)-DIONE

Details on test material:

- Name of test material (as cited in study report): T1201 (3-(2-chloroethyl)-2,4(1H, 3H)-quinazolinedione; CAS no. 5081-87-8)
- Substance type: no data
- Physical state: white solid
- Analytical purity: 100%
- Impurities (identity and concentrations): not applicable
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: 00464885 RT001201G1A251
- Expiration date of the lot/batch: unknown; is excluded from the statement of compliance
- Stability under test conditions: unknown in PEG 300
- Storage condition of test material: at room temperature (20 +/- 5 °C), light protected
- Stability of test item: stable under storage conditions
- Other: no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HanRCC:WIST (SPF) from RCC Ltd., Laboratory Animal Services CH-4414 Fullinsdorf / Switzerland
- Age when treated: 12 weeks
- Weight at study initiation: ranged between 186 to 196 grams
- Fasting period before study: 18 hours (access to water was permitted. Food was provided again approx 3 hours after dosing.
- Housing: standard laboratory conditions, 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): ad libitum, pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 001/06 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland)
- Water (e.g. ad libitum): ad libitum, community tap water from Fullinsdorf
- Acclimation period: 5 days, under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

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


IN-LIFE DATES:
From: 2006-04-04 To: 2006-04-18 (1st 2000 mg/kg treatment)
From: 2006-04-06 To: 2006-04-20 (2nd 2000 mg/kg treatment)

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
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: PEG 300 was found to be a suitable vehicle. The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. This formulation trial is excluded from the GLP statement of compliance.
- Lot/batch no. (if required): 120471944705164
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg

DOSAGE PREPARATION (if unusual): Dose levels are in terms of the test item as supplied by the sponsor. The dose formulations were made shortly before each dosing occasion using a magnetic stirrer and a spatula as homogenizers. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data

Doses:

- one dose: 2000 mg/kg bw

No. of animals per sex per dose:

3 females per group; 2 groups

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
Observation: during the acclimatization period, and 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
Weighing: on days 1 (prior to test), 8, and 15
- Necropsy of survivors performed: yes. All animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were perforemd. No organs or tissues were retained.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: no data

Statistics:

No statistical analysis was used

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: result of two tests

Mortality:

No deaths occurred during the study

Clinical signs:

Slightly ruffled fur was noted in three animals at the 2- and 3-hour reading and persisted in one animal until the 5-hour reading.

Body weight:

The body weights of the animals were within the range commonly recorded for this strain and age.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Other findings:

no data

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of T1201 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. Therefore, the substance is considered not to be classified.