2-(chloromethyl)-4-methylquinazoline

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-07-01 to 2004-07-22

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2000

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

CD 605 XX

IUPAC Name:

CD 605 XX

Test material form:

solid: crystalline

Details on test material:

- Physical state: brown crystalline powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 7-8 weeks
- Weight at study initiation: males 181-205 g, females 130-140 g
- Fasting period before study: in the afternoon of day -1 (at approx. 16:00 h) over night
- Housing: in groups up to three animals of one gender per cage
- Diet (e.g. ad libitum): ad libitum (Kliba No. 3438.0.25, Provimi Kliba SA, CH-4303 Kaiseraugst, Switzerland)
- Water (e.g. ad libitum): ad libitum (municipal tap water; Stadtwerke Biberach)
- Acclimation period: 5 to 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-2
- Humidity (%): 45 - 75
- Air changes (per hr): min. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % aqueous hydroxyethylcellulose

Details on oral exposure:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of prior experience, 200 mg/kg bw was chosen as the initial dose. The second dose was selected based on the animals´ response to 200 mg/kg.

Doses:

200, 2000 mg/kg bw

No. of animals per sex per dose:

200 mg/kg bw: 3 female
2000 mg/kg bw: 3 female
200 mg/kg bw: 3 male

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made once to twice daily. Body weight was recorded on Day -1 and during the observation period, the body weight of all animals was recorded on Day 1, 2, 8 and 15, respectively.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight

Statistics:

None performed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

other: ALD

Effect level:

> 200 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

200 mg/kg: No mortality occurred in either male or female rats.
2000 mg/kg: Two out of three females died. Two rats were found dead in the morning of Day 2. Due to the marked mortality in females, no male rats were treated.

Clinical signs:

other: 200 mg/kg, male: Clinical signs were observed on Day 1 only in all three rats treated and included piloerection (2.5 h to 5.25 h post administration) and sedation (4.0 h to 5.25 h post administration). Rats returned to normal on Day 1 (6.25 h post adminis

Gross pathology:

200 mg/kg: Except slight changes in the uterus of one female animal (horns filled with aqueous liquid), no gross macroscopic alterations were observed at necropsy.
2000 mg/kg: At necropsy of two female animals, which died on Day 1, gross macroscopic changes were observed in the lungs (discoloration), the stomach (discoloration of the mucosa, multiple bleedings in the wall) and the intestines (empty lumen). One animal, in addition, showed alterations in the skin around the nose (red discharge) and in the liver (stasis).
No changes were seen at necropsy of the female animal, which survived the entire study period.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

according to CLP

Conclusions:

An approximate lethal dose (ALD) for the test item between 200 and 2000 mg/kg in rats was determined.
Based on the dose effect relationship the LD 50 was estimated to be 1000 mg/kg bw according to Annex 3b of the replaced OECD 423, adopted in March 1996. Therefore, the substance has to be classified as harmful if swallowed.