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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 July 2017 to 22 September 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3-bis(hydroxymethyl)urea
EC Number:
205-444-0
EC Name:
1,3-bis(hydroxymethyl)urea
Cas Number:
140-95-4
Molecular formula:
C3H8N2O3
IUPAC Name:
1,3-bis(hydroxymethyl)urea
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: 169 g (157 - 173 g)
- Fasting period before study: Diet was withheld from about 17 to 20 hours before start of treatment until 4 hours after administration.
- Housing: group-housed (3 per group) in type IV Makrolon cages, one day before treatment, the rats were single-housed in type III Makrolon cages.
- Diet: maintenance diet (VI534, ssniff Spezialdiaten GmbH. Germany) ad libitum
- Water: Drinking water from the community water supply was offered ad libitum in Makrolon' bottles (BIOSCAPE GmbH, Castrop-Rauxel, Germany). Drinking water was changed at least three times per week.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.0 - 23.3
- Humidity (%): 45.3 - 76.6


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.25% aqueous hydroxypropylcellulose (Methocel K4M Premium solution, 2.5 g/L distilled water)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 g/L
- Justification for choice of vehicle: well tolerated and established standard vehicle

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


CLASS METHOD
- Rationale for the selection of the starting dose: Due to the chemical properties of the test item, mortality was not expected at the highest starting dose of 2000 mg/kg bw. Therefore, the study was started with 2000 mg/kg bw in three female rats and continued with further three females at 2000 mg/kg bw.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On the day of treatment, each animal was observed for mortality and for symptoms of intoxication at scheduled intervals according to the record sheets. On the following days, the rats were examined once daily. Symptoms were recorded individually for each animal. All animals were weighed before treatment (day 1) and on day 2, 4, 6, 8, 11, 13 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was seen.
Clinical signs:
No clinical signs of toxicity were observed.
Body weight:
There were no effects on the body weight development throughout the study.
Gross pathology:
No organ alterations were identified during the gross pathological examination.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an in vivo acute oral toxicity study in rats (Acute-Toxic-Class Method = ATC-Method) according to OECD Guideline 423, a LD50 > 2000 mg/kg bw was determined.
Executive summary:

In an in vivo acute oral toxicity study in Wistar rats (Acute-Toxic-Class Method = ATC-Method) according to OECD Guideline 423, the acute oral toxicity of N,N`-Bis(hydroxymethyl)urea was determined. The study was started with 2000 mg/kg bw in 3 young adult female rats (Crl:WI (Han)). Since no mortality was observed, the test was continued with further 3 females treated with 2000 mg/kg bw. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily for 14 days. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy. No mortality occurred during the course of this study. No clinical signs of toxicity were observed. The body weight development was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations. The test substance has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg bw after single oral administration in female rats.