Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study in accordance with OPPTS 870.1100 and OECD TG

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
version 1987
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): EXP 3982 N-2-hydroxyethylurea
- Physical state: clear yellow liquid
- Analytical purity: aqueous solution containing 57.58 % hydroxyethyl urea
- Impurities (identity and concentrations): not reported
- Composition: aequeous solution containing 57.58 % hydroxyethyl urea
- Purity test date: not reported
- Lot/batch No.: 84714
- Expiration date of the lot/batch: 15 July 2001
- Storage condition of test material: at room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley Inc.
- Age at study initiation: males were about 10 to 11 weeks old; females were about 10 weeks old
- Weight at study initiation: males weighed 298-335 g; females weighed 187-226 g
- Fasting period before study: yes, overnight fasting
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): PMI Certified Rodent Chow #5002 (Purina Mills Inc) ad libitum
- Water (e.g. ad libitum): municipal tap water treated by reverse osmosis ad libitum
- Acclimation period: acclimated to the laboratory conditions for a minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24
- Humidity (%): 30-45
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 3.05 mL/kg
Doses:
3473 mg/kg corresponding to 2000 mg/kg active ingredient
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: clinical observations were made two times on the day of administration and once per day thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: bodyweight was determined on the day of administration, on day 7 and day 14
Statistics:
Not applicable

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 473 mg/kg bw
Based on:
test mat.
Remarks:
aqueous solution containing 57.58 % of the registration item
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality occurred during after oral administration or during the 14-day observation period.
Clinical signs:
Transient incidences of fecal stain, mucoid stools and dark material around the nose
Body weight:
Bodyweight gain was noted in all animals
Gross pathology:
No significant findings; one isolated incidence of foci on the thymus of one animal was observed that was considered to be not related to treatment

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was not acutely toxic to rats after single oral administration and the LD50 was greater than 3473 mg/kg (> 2000 mg/kg for hydroxyethyl urea).
Executive summary:

The acute oral toxicity of the test substance EXP 3982 N-2-hydroxyethylurea containing 57.58% of the active ingredient hydroxyethyl urea was studied under GLP in a study according to OECD TG 401. After a preliminary study with doses ranging from 868 to 3473 mg/kg (corresponding to 500 to 2000 mg/kg active ingredient), a final limit test was conducted with a single dose of 3473 mg/kg corresponding to 2000 mg/kg active ingredient. Five male rats (10 to 11 weeks old, weighing 298 to 335 g) and five female rats (10 weeks old, weighing 187 to 226 g) of the Sprague-Dawley strain were fasted overnight and received a single oral dose of the test material by gavage at a volume of 3.05 mL/kg. Animals were housed individually in suspended cages and observed for a period of 14 days. Animals received food and drinking water ad libitum. At the end of the observation period the animals were sacrificed and a gross necropsy was performed on all animals. No mortality occurred after dosing or during the 14-day observational period. No significant clinical observations and findings at necropsy were made. Bodyweight development was normal. The LD50 value was greater than 3473 mg/kg for the formulation, which corresponds to >2000 mg/kg for the active ingredient.

Based of the lack of any significant toxicity at 2000mg/kg, hydroxyethyl urea is not classified for acute dermal toxicity according to GHS.