1,3-diethyldiphenylurea

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18.4. - 25.4.2001

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

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,3-diethyldiphenylurea

EC Number:

201-645-2

EC Name:

1,3-diethyldiphenylurea

Cas Number:

85-98-3

Molecular formula:

C17H20N2O

IUPAC Name:

1,3-diethyl-1,3-diphenylurea

Details on test material:

- Name of test material (as cited in study report): Centralit
- Physical state: white solid powder
- Analytical purity: 99.93%
- Impurities (identity and concentrations): sec. and terc. amines 0.06%, volatile substances 0.01%
- Lot/batch No.: 0271199/B
- Storage condition of test material: the substance was stored in dark, at laboratory conditions

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system 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 libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity relative (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12-hour light/12 hour dark

STUDY TIME SCHEDULE
Experimental part of study: 18.4.-25.4. 2001

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

PREPARATION OF APPLICATION FORM
The 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:

Doses:

500, 700, 1000, 1500 mg/kg bw

No. of animals per sex per dose:

5 females per dose

Control animals:

no

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

Statistics:

Numeric value of toxicity was defined by Bliss method, using computer program PROBIT (VUOS 1991).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

780.9 mg/kg bw

Based on:

test mat.

95% CL:

685.5 - 889.6

Mortality:

Dose 700 mg/kg
2 animals after 2.15 and 5.5 hrs after application

Dose 1000 mg/kg
4 animals 0.45 hrs after application

Dose 1500 mg/kg
all animals died 0.15 - 04 hrs after application

Clinical signs:

other: Dose 500 mg/kg 30 minutes after application: Piloerection, skin anaemia, discomfort, excitation, tremor, increased reactivity 2nd day: no clinical changes Dose 700 mg/kg 30 minutes after application: Skin anaemia, discomfort, clonus, torpor, increased re

Gross pathology:

Dose 500 mg/kg
Without pathological changes

Dose 700 mg/kg
3 survivors - without pathological changes
2 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/kg
Mild lung congestion, stomach anaemia, flatulence, intestine anaemia, liver congestion

Dose 1500 mg/kg
Mild lung congestion, mild intestine anaemia, liver congestion

Any other information on results incl. tables

-

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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.