3-(dimethylamino)propylurea

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

The studies were performed in accordance with EC Directives 84/449 (Official Journal of the European Communities 27, 1984, L 251, 96).

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-(dimethylamino)propylurea

EC Number:

401-950-2

EC Name:

3-(dimethylamino)propylurea

Cas Number:

31506-43-1

Molecular formula:

C6H15N3O

IUPAC Name:

[3-(dimethylamino)propyl]urea

Test material form:

liquid: viscous

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

We conducted the acute toxicity experiment with young adult SPF-bred Wistar rats (Bor strain: WISW (SPF Cpb), breeder: Winkelmann, Borchen).
This rat is the species of choice for studying acute oral toxicity in mammals.
The male and female rats were approximately 9 and 14 weeks old respectively at the start of the experiment.
The male animals had an average baseline weight of 162 g, the female animals 173 g.
The distribution of the animal weights was less than 20% from the mean.
The females were nullipara and not pregnant.
The health status of the animals was checked prior to the start of the experiment. Only symptom-free, healthy animals were used for the experiment.
Five rats were used per dose and sex.
The rats were kept in groups of 5 in conventional fashion in Makrolon cages of Type III on dust-free wood granulate (manufacturer: Forsbach GmbH, Solingen) at an ambient temperature of 22 +/– 2 degrees Celsius and a 12-hour light/dark cycle (artificial lighting from 6:00 a.m. to 6:00 p.m. MET) and a relative humidity of approximately 50 +/– 10%.
As food, the animals received "Altromin 1324 – Maintenance Diet for Rats and Mice" in pellet form (manufacturer: Altromin GmbH, Lage) along with tap water ad libitum (water bottles).

Feed, water and litter are checked for harmful substances and impurities at regular intervals. The documents are filed at Bayer AG, Central Office for Questions Regarding Experimental Animals, Wuppertal.

The animals were acclimated for 5 days prior to the start of the experiment.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

The feed was removed from approximately 16 hours before to 4 hours after the application, the rest of the time it was freely available.
The substance was formulated in Lutrol (manufacturer: Merck-Schuchard, Art. No.: 807485) at room temperature and administered once intragastrically to 5 male and 5 female animals by using a rigid metal stomach probe at a constant application volume of 10 ml/kg of body weight.
The test substance was formulated immediately prior to the start of the experiment in the polyethylene glycol 400 (Lutrol) application medium, whereby each concentration was prepared separately. Because of the brief period of time between preparation and application, no analytical studies were performed with regard to stability in the application medium. A homogeneous mixture was obtained through mixing in a magnetic stirrer.

Doses:

The following dosages were used: 3178, 5125 mg/kg of body weight.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The studies were performed in accordance with EC Directives 84/449 (Official Journal of the European Communities 27, 1984, L 251, 96).
All the animals were allotted to the treatment groups by means of a random list based on random numbers. A label was affixed to each cage, listing the substance name, type of animal, dosage, study number, type of application, sex, and the number of animals.
Identification within a cage was carried out by marking the fur with picric acid.
The feed was removed from approximately 16 hours before to 4 hours after the application, the rest of the time it was freely available.
The substance was formulated in Lutrol (manufacturer: Merck-Schuchard, Art. No.: 807485) at room temperature and administered once intragastrically to 5 male and 5 female animals by using a rigid metal stomach probe at a constant application volume of 10 ml/kg of body weight.
The test substance was formulated immediately prior to the start of the experiment in the polyethylene glycol 400 (Lutrol) application medium, whereby each concentration was prepared separately. Because of the brief period of time between preparation and application, no analytical studies were performed with regard to stability in the application medium. A homogeneous mixture was obtained through mixing in a magnetic stirrer.
On the day of the application, the animals were inspected multiple times, twice daily during the 14-day observation period (once on weekends and holidays); as this was done, the type, start, duration and intensity of the clinical symptoms were logged, and dead animals were removed as necessary. The time of death of dead animals was logged.
Immediately before the application, one week after and at the end of the 14-day observation period, the surviving animals were weighed individually. The calculation of each animal's application volume was performed using the body weight recorded immediately before the application.
All of the animals that died during the experiment and all animals that were killed at the end of the experiment by means of deep diethylether narcosis were evaluated pathologically and anatomically. Dissection protocols were prepared for all animals that died or were killed.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 125 mg/kg bw

Based on:

test mat.

Mortality:

The LD50 was approximately 5125 mg/kg of body weight.

Clinical signs:

other: The following symptoms were observed following one-time administration of the 5125 mg/kg dosages: Decline in general condition, sedation, ruffled fur. Intensity, timing of the occurrence of the symptoms and the incidence of death cases in the individuall

Gross pathology:

In the pathological-anatomical evaluation of the animals that died from the 5125 mg/kg dosage, the gastric mucous membrane was coated and severely reddened, the intestines were slightly reddened.
The animals from the 3178 and 5125 mg/kg dosages that were terminated and examined at the end of the experiment were macroscopically normal

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for male and female rats was approximately 5125 mg/kg (5.0 ml/kg) of body weight.
The test substance can thus be considered as relatively non-toxic following oral exposition, and accordingly is not to be classified in accordance with the EC Directive.

Executive summary:

Using N-(3-(dimethylamino)-propyl)urea = HST 2844, acute toxicological studies were performed involving oral administration to male and female Wistar rats.

The LD₅₀for male and female rats was approximately 5125 mg/kg (5.0 ml/kg) of body weight.

Beginning at 5125 mg/kg, the following were observed as symptoms of poisoning:

Decline in general condition, sedation, ruffled fur, retarded growth in one female animal.

A dose of 3178 mg/kg was tolerated by female and male rats with no symptoms.