2-Propen-1-one, 3-(dimethylamino)-1-(3-pyridinyl)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 September 1999 - 1 October 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

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

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

434-770-8

EC Name:

-

Cas Number:

55314-16-4

Molecular formula:

C10 H12 N2 O1

IUPAC Name:

3-(dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one

Details on test material:

Identification: STI571 Y5A
Test substance code: 1550515
Description: Brown solid
Batch: 992301
Purity: 98.6%
Test substance storage: In refrigerator in the dark
Stability under storage conditions: Stable

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, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 10-11 weeks old) were selected.
- Weight at study initiation: 207-225 gram for females, 335-362 gram for males. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per sex per cage in labelled polycarbonate cages containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany).
- Diet: ad libitum, standard pelleted laboratory animal diet (Carfil Quality BVBA, Oud-Turnhout, Belgium).
- Water: ad libitum.
- Acclimation period: Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
A controlled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21°C, a relative humidity of 30-70% and 12 hours artificial fluorescent light and 12 hours dark per day.

IN-LIFE DATES: From: 8 September 1999 to: 1 October 1999

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of ml/kg body weight.
- Justification for choice of vehicle: The vehicle was selected based on a pretest performed at NOTOX.
- Batch no.: 992301
- Purity: 98.6%

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

2000 mg/kg body weight.
200 mg/kg body weight.

No. of animals per sex per dose:

3 males and 3 females received 2000 mg/kg body weight. An additional group of 3 males was dosed at 200 mg/kg body weight.

Control animals:

no

Details on study design:

- Duration of observation period following administration: until day 15
- Frequency of observations and weighing: Days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg: 1/3 females and 2/3 males.
200 mg/kg (males only): no mortality.

Clinical signs:

other: 2000 mg/kg Females: Lethargy, ventral lateral recumbency, uncoordinated movements, slow breathing and watery discharge from the eyes. 2000 mg/kg Males: Lethargy, ventral lateral recumbency, hunched posture, uncoordinated movements, shallow respiration, pi

Gross pathology:

Macroscopic post mortem examination of the animals that were found dead or sacrificed for ethical reasons during the study revealed:
stomach: thickening of the limiting ridge; urinary bladder: enlarged and several reddish focus/foci; prostate: enlarged, dark red or reddish discolouration, moist; seminal vesicles: enlarged and/or moist; spleen: reduced in size; body cavities containing watery fluid; thymus: light red focus/foci.

No treatment related abnormalities were found at macroscopic examination of the surviving animals.

Other findings:

Not applicable.

Any other information on results incl. tables

Not applicable.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information if swallowed (R22) Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of STI571 Y5A in Wistar rats was established to be within the range or 200-2000 mg/kg body weight. Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), 8TI571 Y5A should be labelled as: harmful if swallowed (R22).