Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18.4. - 25.4.2001
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was carried out in accordance with internationally valid GLP principles.

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
according to
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Details on test material:
- Name of test material (as cited in study report): Centralit- Physical state: white solid powder- Analytical purity: 99.93%- Lot/batch No.: 0271199/B- Storage condition of test material: the substance was stored in dark, at laboratory conditions

Test animals

Details on test animals and environmental conditions:
TEST ANIMALS- Source: TOP VELAZ s.r.o., Praha, Czech Republic- Weight at study initiation: 158-183 g- Fasting period before study: 20 h- Housing: 5 animals in one plastic breeding cage VELAZ T4- Diet (e.g. ad libitum): standard feeding mixture ST-1 ad libitum- Water (e.g. ad libitum): drinking tap water ad libitumENVIRONMENTAL CONDITIONS- Temperature (°C): 20-24°C- Humidity relative (%): 30-70%- Photoperiod (hrs dark / hrs light): 12-hour light/12 hour darkSTUDY TIME SCHEDULEExperimental part of study: 18.4.-25.4. 2001

Administration / exposure

Route of administration:
oral: gavage
olive oil
Details on oral exposure:
PREPARATION OF APPLICATION FORMThe single volume of administered suspension was 1mL/100 g of animal body weight.VEHICLE- Concentration in vehicle:- Amount of vehicle (if gavage):- Justification for choice of vehicle:- Lot/batch no. (if required):- Purity:MAXIMUM DOSE VOLUME APPLIED:DOSAGE PREPARATION (if unusual):CLASS METHOD (if applicable)- Rationale for the selection of the starting dose:
500, 700, 1000, 1500 mg/kg bw
No. of animals per sex per dose:
5 females per dose
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days- Mortality: daily- Body weight recording: before application, on the 8th day of the study and at the end of the study- Clinical examination: the first day: twice (30 minutes and 3 hours after application), the second day: twice (in the morning and in the afternoon) and daily thereafter for 14 days- Necropsy of survivors performed: yes
Numeric value of toxicity was defined by Bliss method, using computer program PROBIT (VUOS 1991).

Results and discussion

Effect levels
Dose descriptor:
Effect level:
780.9 mg/kg bw
Based on:
test mat.
95% CL:
685.5 - 889.6
Dose 700 mg/kg2 animals after 2.15 and 5.5 hrs after applicationDose 1000 mg/kg4 animals 0.45 hrs after applicationDose 1500 mg/kgall animals died 0.15 - 04 hrs after application
Clinical signs:
Dose 500 mg/kg30 minutes after application: Piloerection, skin anaemia, discomfort, excitation, tremor, increased reactivity2nd day: no clinical changesDose 700 mg/kg30 minutes after application: Skin anaemia, discomfort, clonus, torpor, increased reactivity2nd day: no clinical changesDose 1000 mg/kgDiscomfort, clonospasm, increased reactivityDose 1500 mg/kgTremor, spasm, vocalization, dyspnoe, vocalization
Gross pathology:
Dose 500 mg/kgWithout pathological changesDose 700 mg/kg3 survivors - without pathological changes2 died animal - skin anaemia, mild lung congestion, intestine anaemia, mild liver, congestion, heart-block in systole (probably consequence of abdominal muscules contraction)Dose 1000 mg/kgMild lung congestion, stomach anaemia, flatulence, intestine anaemia, liver congestionDose 1500 mg/kgMild lung congestion, mild intestine anaemia, liver congestion

Any other information on results incl. tables


Applicant's summary and conclusion

Interpretation of results:
Migrated informationCriteria used for interpretation of results: EU
The test substance CENTRALIT is according to results of acute oral toxicity classified as harmful. The test substance caused clinical signs of intoxication – increase neuro-muscles irritability resulted in spasm. Pathological findings were insignificant.
Executive summary:

The aim of the study was to investigate acute toxic effects of the test substance Centralit, after a single oral administration to Wistar rats (females only). Result follows in test protocol No. 0127 (March, the 3rd, 2001), when after performing of limit test, higher sensitivity for females was found out.

The testing was performed according to Regulation of Ministry of health of the Czech Republic No. 251/1998 Sb., the Method B.1: Acute Oral Toxicity (per os). This method corresponds with the guideline OECD No. 401 (1987).

According to the study results, the value of LD50 (oral) for female rats is 780.9 mg/kg of body weight.