1-Butanone, 2-(dimethylamino)-2-[(4-methylphenyl)methyl]-1-[4-(4-morpholinyl)phenyl]-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18.10.2001 - 23.11.2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

438-340-0

EC Name:

-

Cas Number:

119344-86-4

Molecular formula:

C24 H32 N2 O2

IUPAC Name:

2-(dimethylamino)-2-[(4-methylphenyl)methyl]-1-[4-(morpholin-4-yl)phenyl]butan-1-one

Details on test material:

- Physical state: solid
- Analytical purity: commercial grade
- Lot/batch No.: 766/130
- Expiration date of the lot/batch: 31-AUG-2003
- Stability under test conditions: 4 hours
- Storage condition of test material: at room temperature (range of 17-23°C). In a closed container in the dark.

Test animals

Species:

rat

Strain:

other: HanBrl: Wist

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Animal Breeding Division, Fullinsdorf / Switzerland
- Age at study initiation: Males: 8 weeks, Females: 10 weeks
- Mean weight at study initiation: Females: 174.27 g; Males: 203.6 g
- Fasting period before study: 16 to 20 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.
- Housing: three per sex in Makrolon type-4 cages
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 73/01 (Provimi Kliba AG, Kaiseraugst/ Switzerland), ad libitum.
- Water (e.g. ad libitum): Community tap-water, from Itingen ad libitum.
- Acclimation period: 6 days

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

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: The vehicle was chosen after a non-GLP solubility trial performed before experimental starting date.
- Lot/batch no. (if required): 424718/142701

DOSAGE PREPARATION (if unusual): The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). The mixtures were prepared using a glass stick first then a magnetic stirrer.
Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
Mortality / Viability: Daily during acclimatization and twice daily during days 1-15.
Body weights: On test days 1 (pre-administration), 8 and 15.
Clinical signs: Daily during acclimatization and at least four times on test day 1 after the test item administration. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy: All surviving animals were killed at the end of the observation period and discarded after macroscopic examinations were performed. No organs or tissues were retained.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality and no clinical signs were observed.

Mortality:

No deaths occurred.

Clinical signs:

other: Slight emaciation was evident in one female on the test days 5 and 6. All other animals were without clinical signs.

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material was determined to have an acute oral LD50 >2000 mg/kg bw (in the rat) under the conditions of the test. The substance is not orally toxic.

Executive summary:

In this guideline (OECD 423) study conducted with GLP, the acute oral LD50 of the test material (EC 438-340-0) to rats was determined to be >2000 mg/kg bw (both sexes). The test material was administered via gavage at a dose of 2000 mg/kg bw. The result of the test was not sufficient to trigger classification and labelling of the test material for acute toxicity under the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).