Registration Dossier

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

Constituent 1
Chemical structure
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
Chemical structure
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
Chemical structure
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 The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.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:
All animals were normal during the entire observation period.
Body weight:
All animals gained weight in both weeks p.a.

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.