Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
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 OECD TG 402

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 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal 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 Spargue Dawley Inc.
- Age at study initiation: 11 weeks
- Weight at study initiation: males: 330-365 g, females: 211 - 243 g
- Fasting period before study: No
- 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 (%): 36 -45
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure:
- % coverage: 10% of body surface area
- Type of wrap if used: gauze dressing backed with a plastic wrap, elastic wrap over trunk and test area

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test article removes using gauze moistened with deionized waster followed by dry gauze
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3473 mg/kg (corresponding to 2000 mg/kg active ingredient)
- Constant volume or concentration used: yes
Duration of exposure:
24 h
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 and weighing: daily examinations for erythema and edema, daily clinical observations, twice daily mortality check, weighing on day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights

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 the limit test.
Clinical signs:
Few faeces, dark material around the facial area, dermal irritation at site of test material application
Body weight:
Slight body weight loss in one male and one female during day 0 to 7 body weight interval. Body weight gain noted for all other animals during test period.
Gross pathology:
No significant gross internal findings at necropsy

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this test, the acute dermal LD50 was estimated to be greater than 3473 mg for the aqueous solution EXP 3982 N-2-hydroxyethylurea per kg in the rat. This corresponds to a LD50 of > 2000 mg/kg for hydroxyethyl urea.
Executive summary:

The single-dose dermal toxicity of the test substance EXP 3982 N-2-hydroxyethylurea containing 57.58% of the active ingredient hydroxyethyl urea was evaluated in rats in accordance with OECD TG 402. The study was performed under GLP.

A limit test was performed in which one group of five male and five female rats received a single dermal administration of the test substance at a dose of 3573 mg/kg formulation (2000 mg/kg active ingredient). Following dosing, the test animals were observed daily and weighed weekly. A gross necropsy examination was performed on all animals at the time of scheduled euthanasia (day 14).

No mortality occurred during the limit test. Clinical abnormalities observed during the study included few faeces and dark material around the facial area. Dermal irritation was noted at the site of test article application. A slight body weight loss was noted for one male and one female during the day 0 to 7 body weight interval. Body weight gain was noted for all other animals during the test period. No significant gross internal findings were observed at necropsy on study day 14.

Under the conditions of this test, the acute dermal LD50 of EXP 3982 N-2-hydroxyethylurea was estimated to be greater than 3473 mg/kg in the rat. This corresponds to a LD50 of > 2000 mg/kg for hydroxyethyl urea. Based of the lack of any significant toxicity at 2000mg/kg, hydroxyethyl urea is not classified for acute dermal toxicity according to GHS.