1,1-dimethylurea

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - July 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,1-dimethylurea

EC Number:

209-957-0

EC Name:

1,1-dimethylurea

Cas Number:

598-94-7

Molecular formula:

C3H8N2O

IUPAC Name:

1,1-dimethylurea

impurity 1

Reference substance name:

Urea

EC Number:

200-315-5

EC Name:

Urea

Cas Number:

57-13-6

Molecular formula:

CH4N2O

IUPAC Name:

urea

impurity 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

dihydrogen oxide

Test material form:

solid: crystalline

Specific details on test material used for the study:

- Analytical purity: at least 98 %
- Impurities (identity and concentrations): max. 2 % Urea, max. 0.2 % Isopropanol, max. 0.5 % diethyleneglycolmonoethylether
- Lot/batch No.: KG 03-13

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Remarks:

Crl:CD(SD)IGS BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 97633 Sulzfeld, Germany.
- Age at study initiation: approx. 8 weeks at the time of administration
- Weight at study initiation: 184 - 202 g
- Housing: Single caging in Makrolon cages type III (39 cm x 23 cm bottom area, 18 cm height). Wire mesh lids. Sanitation of cages once a week.
- Diet (e.g. ad libitum): Altromin 1324 forte, gamma irradiated with 25 kGy 60Co, ad libitum (Producer: Altromin GmbH, 32791 Lage, Germany). The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.
- Water (e.g. ad libitum): Tap water from an automatic watering system, ad libitum.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 21.9 °C (continuous control and recording)
- Humidity (%): Average of 66.5 % (continuous control and recording)
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.
- Air exchanges: 12 per hour

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: The test substance was enough soluble in water and water shall be used preferably, according to the guideline.

MAXIMUM DOSE VOLUME APPLIED:
10mL per kg body weight

Doses:

1st and 2nd step: 300 mg/kg bw
3rd and 4th step: 2000 mg/kg bw

No. of animals per sex per dose:

3 animals per step and 6 animals per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

Clinical observations:
Observations were performed within the periods 0 - 0.5, 0.5 - 1, 1 - 2, 2 - 4 and 4 - 6 hours after administration (p.a.) of the test substance and then at least once a day for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.

Body weights and body weight gain:
Body weights were determined before administration, 7 days p.a., 14 days p.a.
Body weight gain was calculated for each week of the study, i.e. between 0 and 7 days p.a. and 7 and 14 days p.a.

Necropsy:
The animals were killed by inhalation of 80 % CO2 + 20 % air 14 days p.a. and subjected to a necropsy including a gross pathological examination.

Statistics:

no data

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the scheduled termination of the study.

Clinical signs:

other: All animals were normal during the entire observation period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No toxic effects of the test substance 1,1-Dimethylurea were noted by signs in life and post mortem. No mortality occured. According to the decision tree of the OECD-Guideline 423 the LD50 oral is estimated to be higher than 2000 mg/kg body weight in rats.

Executive summary:

The acute toxic effects of 1,1 -Dimethylurea were investigated after a single peroral administration to rats. The study was performed according to OEDC Guideline 423.

1,1 -Dimethylurea was administered once as solution in deionised water, given orally via gavage to female rats. The dosing was performed sequentially to groups of 3 animals per step using a starting dose of 300 mg per kg body weight and 2000 mg per kg body weight as the second dose. The dose volume was 10 mL per kg body weight for all groups. Observations were performed within the periods 0 - 0.5, 0.5 - 1, 1 - 2, 2 - 4 and 4 - 6 hours after administration (p.a.) of the test substance and then at least once a day for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions. Body weights were determined before administration, 7 days p.a., 14 days p.a. Body weight gain was calculated for each week of the study, i.e. between 0 and 7 days p.a. and 7 and 14 days p.a. The animals were killed by inhalation of 80 % CO2 + 20 % air 14 days p.a. and subjected to a necropsy including a gross pathological examination.

No toxic effects of the test substance 1,1-Dimethylurea were noted by signs in life and post mortem. No mortality occured. According to the decision tree of the OECD-Guideline 423 the LD50 oral is estimated to be higher than 2000 mg/kg body weight in rats.